Updated on 2025/03/23

写真a

 
IWASAKI,Yasuhiko
 
Organization
Faculty of Chemistry, Materials and Bioengineering Professor
Title
Professor
Contact information
メールアドレス
External link

Degree

  • 博士(工学)

Research Interests

  • バイオミメティクス

  • 表面改質

  • 高分子合成

  • バイオマテリアル

Research Areas

  • Nanotechnology/Materials / Polymer chemistry

  • Nanotechnology/Materials / Polymer materials

  • Nanotechnology/Materials / Bio chemistry

  • Life Science / Biomedical engineering

  • Life Science / Biomaterials

Education

  • Nihon University   Graduate School, Division of Science and Engineering

    1993.4 - 1995.3

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    Country: Japan

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  • Nihon University   Graduate School, Division of Science and Engineering

    1995

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  • Nihon University   Faculty of Science and Technology

    1989.4 - 1993.3

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Research History

  • Kansai University   Faculty of Chemistry , Materials and Bioengineering   Professor

    2011.4

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  • Kansai University   Faculty of Chemistry , Materials and Bioengineering   Associate Professor

    2007.4 - 2011.3

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  • Tokyo Medical and Dental University   Institute of Biomaterials and Bioengineering   Associate Professor (as old post name)

    1999.4 - 2007.3

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  • Tokyo Medical and Dental University   Associate Professor (as old post name)

    1998.7 - 1999.3

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  • Tokyo Medical and Dental University   Research Assistant

    1995.10 - 1998.6

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  • Tokyo Medical and Dental University

    1995.4 - 1995.9

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Professional Memberships

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Committee Memberships

  • 高分子学会 医用高分子研究会   運営委員長  

    2024.4 - Present   

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  • 日本バイオマテリアル学会   理事  

    2013.11 - Present   

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    Committee type:Academic society

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  • e-Polymers   Editorial Advisory Board  

    2011 - Present   

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  • 日本バイオマテリアル学会   編集委員  

    2006.4 - 2024.3   

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Papers

  • Microgel-Based Smart Materials: How Do You Design a Microgel? Reviewed

    Yota Okuno, Yasuhiko Iwasaki

    Langmuir   2025.3

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1021/acs.langmuir.4c04604

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  • Headset biofluorometric system for acetone vapor from the ear canal Reviewed

    Geng Zhang, Kenta Ichikawa, Kenta Iitani, Yasuhiko Iwasaki, Kohji Mitsubayashi

    Sensors and Actuators B: Chemical   427   137220 - 137220   2025.3

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    Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1016/j.snb.2024.137220

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  • Handheld biofluorometric system for acetone in the exhaled breath condensates Reviewed

    Geng Zhang, Kenta Ichikawa, Kenta Iitani, Yasuhiko Iwasaki, Kohji Mitsubayashi

    The Analyst   2025

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    Publishing type:Research paper (scientific journal)   Publisher:Royal Society of Chemistry (RSC)  

    As a marker of human metabolism, acetone is important for lipid metabolism monitoring and early detection of diabetes. In this study, we developed a handheld acetone biosensor based on fluorescence...

    DOI: 10.1039/d4an01281j

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  • Biofluorometric Acetone Gas Sensor of Sub-ppbv Level Sensitivity Reviewed

    Kenta Iitani, Naohiro Ishizuki, Yuka Matsuhashi, Kumi Yokota, Kenta Ichikawa, Koji Toma, Takahiro Arakawa, Yasuhiko Iwasaki, Kohji Mitsubayashi

    Analytical Chemistry   2024.12

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    Publishing type:Research paper (scientific journal)   Publisher:American Chemical Society (ACS)  

    DOI: 10.1021/acs.analchem.4c03816

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  • Suppression of bone resorption in ovariectomized mice using estrogen-immobilized polyphosphodiesters Reviewed

    Yasuhiko Iwasaki, Sota Fukaura, Shun Mabuchi, Yota Okuno, Atsushi Yokota, Masashi Neo

    Materialia   2024.6

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    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.mtla.2024.102166

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  • In Vitro Performance of a Long-Range Surface Plasmon Hydrogel Aptasensor for Continuous and Real-Time Vancomycin Measurement in Human Serum Reviewed

    Yui Taguchi, Koji Toma, Kenta Iitani, Takahiro Arakawa, Yasuhiko Iwasaki, Kohji Mitsubayashi

    ACS Applied Materials & Interfaces   2024.5

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    Publishing type:Research paper (scientific journal)   Publisher:American Chemical Society (ACS)  

    DOI: 10.1021/acsami.4c03805

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  • Creating Anti‐Biofouling Surfaces by Degradable Main‐chain Polyphosphoester Polymer Brushes Reviewed

    Maria Brió Pérez, Diego A. Resendiz‐Lara, Yuma Matsushita, Sachiro Kakinoki, Yasuhiko Iwasaki, Mark A. Hempenius, Sissi de Beer, Frederik R. Wurm

    Advanced Functional Materials   2024.4

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    <jats:title>Abstract</jats:title><jats:p>The implementation of polymer brush coatings has proven crucial in biomedical and biotechnological applications for controlling biological interactions. Despite the extensive research and use of synthetic polymer coatings, concerns regarding their long‐term non‐biodegradability have arisen. This issue is significant as non‐degradable polymers can lead to complications such as inflammatory responses and bioaccumulation, highlighting the need for polymers that degrade in a controlled manner. To address this, polyphosphonate brushes are synthesized as anti‐biofouling coatings on silicon surfaces via controlled surface‐initiated organocatalytic ring‐opening polymerization (SI‐ROP) of cyclic phospholanes. 2‐Ethyl‐2‐oxo‐1,3,2‐dioxaphospholane and 2‐hexyl‐2‐oxo‐1,3,2‐dioxaphospholane are chosen as the monomers to prepare hydrophilic and hydrophobic brushes with thicknesses up to 55 nm, with a proven degradability in aqueous media. In addition, protein adsorption, bacterial adhesion, and biofilm formation are investigated as a function of the polyphosphonate side chain. Compared to non‐coated surfaces and polyester brushes, hydrophilic poly(2‐ethyl‐2‐oxo‐1,3,2‐dioxaphospholane) brushes have an enhanced resistance toward fouling of albumin, fibrinogen, and diluted human serum proteins, as well as toward <jats:italic>Escherichia coli</jats:italic> and <jats:italic>Staphylococcus aureus</jats:italic> bacteria. The stability and anti‐biofouling performance of hydrophilic polyphosphonate brushes position them as an attractive option as degradable materials for anti‐biofouling matrices on medical devices and/or lubricious coatings for artificial implant technologies.</jats:p>

    DOI: 10.1002/adfm.202316201

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  • Long-range surface plasmon hydrogel aptasensor for sensitive, selective, and continuous measurement of vancomycin Reviewed

    Yui Taguchi, Koji Toma, Kenta Iitani, Takahiro Arakawa, Yasuhiko Iwasaki, Kohji Mitsubayashi

    Sensors and Actuators B: Chemical   135882 - 135882   2024.4

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1016/j.snb.2024.135882

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  • Direct Fabrication of Glycoengineered Cells via Photoresponsive Thiol-ene Reaction. Reviewed International journal

    Akihisa Otaka, Taisuke Hirota, Yasuhiko Iwasaki

    ACS biomaterials science & engineering   2024.3

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    Three-dimensional printing of cell constructs with high-cell density, shape fidelity, and heterogeneous cell populations is an important tool for investigating cell sociology in living tissues but remains challenging. Herein, we propose an artificial intercellular adhesion method using a photoresponsive chemical cue between a thiol-bearing polymer and a methacrylate-bearing cell membrane. This process provided cell fabrication containing 108 cells/mL, embedded multiple cell populations in one structure, and enabled millimeter-sized scaleup. Our approach allows for the artificial cell construction of complex structures and is a promising bioprinting strategy for engineering tissues that are structurally and physiologically relevant.

    DOI: 10.1021/acsbiomaterials.3c01987

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  • Encapsulation of multiple enzymes within a microgel via water-in-water emulsions for enzymatic cascade reactions Reviewed

    Yota Okuno, Yasuhiko Iwasaki

    Soft Matter   2024

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1039/D3SM01309J

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  • Photoassisted Surface Modification with Zwitterionic Phosphorylcholine Polymers for the Fabrication of Ideal Biointerfaces Invited Reviewed

    Yasuhiko Iwasaki

    Langmuir   2023.11

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    Authorship:Corresponding author   Publishing type:Research paper (scientific journal)  

    DOI: 10.1021/acs.langmuir.3c02696

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  • Enhanced sensitivity of a fluorometric biosensor for alcohol metabolites with an enzymatic cycling reaction Reviewed

    Geng Zhang, Yuki Maeno, Kenta Iitani, Takahiro Arakawa, Yasuhiko Iwasaki, Koji Toma, Kohji Mitsubayashi

    Sensors and Actuators B: Chemical   2023.11

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.snb.2023.135031

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  • Effect of phosphodiester composition in polyphospshoesters on the inhibition of osteoclastic differentiation of murine bone marrow mononuclear cells Reviewed

    Sota Fukaura, Yasuhiko Iwasaki

    Journal of Biomaterials Science, Polymer Edition   2023.8

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    Authorship:Last author, Corresponding author   Publishing type:Research paper (scientific journal)  

    DOI: 10.1080/09205063.2023.2244737

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  • Gas-Phase Biosensors (Bio-Sniffers) for Measurement of 2-Nonenal, the Causative Volatile Molecule of Human Aging-Related Body Odor Reviewed

    Kenta Iitani, Hidehisa Mori, Kenta Ichikawa, Koji Toma, Takahiro Arakawa, Yasuhiko Iwasaki, Kohji Mitsubayashi

    Sensors   23 ( 13 )   5857 - 5857   2023.6

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    Publishing type:Research paper (scientific journal)   Publisher:MDPI AG  

    The molecule 2-nonenal is renowned as the origin of unpleasant human aging-related body odor that can potentially indicate age-related metabolic changes. Most 2-nonenal measurements rely on chromatographic analytical systems, which pose challenges in terms of daily usage and the ability to track changes in concentration over time. In this study, we have developed liquid- and gas-phase biosensors (bio-sniffers) with the aim of enabling facile and continuous measurement of trans-2-nonenal vapor. Initially, we compared two types of nicotinamide adenine dinucleotide (phosphate) [NAD(P)]-dependent enzymes that have the catalytic ability of trans-2-nonenal: aldehyde dehydrogenase (ALDH) and enone reductase 1 (ER1). The developed sensor quantified the trans-2-nonanal concentration by measuring fluorescence (excitation: 340 nm, emission: 490 nm) emitted from NAD(P)H that was generated or consumed by ALDH or ER1. The ALDH biosensor reacted to a variety of aldehydes including trans-2-nonenal, whereas the ER1 biosensor showed high selectivity. In contrast, the ALDH bio-sniffer showed quantitative characteristics for trans-2-nonenal vapor at a concentration range of 0.4–7.5 ppm (with a theoretical limit of detection (LOD) and limit of quantification (LOQ) of 0.23 and 0.26 ppm, respectively), including a reported concentration (0.85–4.35 ppm), whereas the ER1 bio-sniffer detected only 0.4 and 0.8 ppm. Based on these findings, headspace gas of skin-wiped alcohol-absorbed cotton collected from study participants in their 20s and 50s was measured by the ALDH bio-sniffer. Consequently, age-related differences in signals were observed, suggesting the potential for measuring trans-2-nonenal vapor.

    DOI: 10.3390/s23135857

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  • Well‐Defined Anisotropic Self‐Assembly from Peptoids and Their Biomedical Applications Reviewed

    Yota Okuno, Yasuhiko Iwasaki

    ChemMedChem   2023.5

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Wiley  

    DOI: 10.1002/cmdc.202300217

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  • Cover Image

    Kenjiro Kiyono, Shun Mabuchi, Akihisa Otaka, Yasuhiko Iwasaki

    Journal of Biomedical Materials Research Part A   2023.5

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/jbm.a.37546

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  • Bone‐targeting polyphosphodiesters that promote osteoblastic differentiation Reviewed International journal

    Kenjiro Kiyono, Shun Mabuchi, Akihisa Otaka, Yasuhiko Iwasaki

    Journal of Biomedical Materials Research Part A   2023.1

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    Polymers for pharmaceutical use have been attractive in medical treatments because of the conjugation of multifunctional components and their long circulation time in the blood stream. Bone-targeted drug delivery systems are also no exceptional, and several polymers have been proposed for the treatment of bone diseases, such as cancer metastasis and osteoporosis. Herein, we report that polyphosphodiesters (PPDEs) have a potential to enhance osteoblastic differentiation, and they have a targeting ability to bone tissues in vivo. Two types of PPDEs, poly (ethylene sodium phosphate) (PEP•Na) and poly (propylene sodium phosphate) (PPP•Na), have been synthesized. Regardless of the alkylene structure in the main chain of PPDEs, the gene expression of osteoblast-specific transcription factors and differentiation markers of mouse osteoblastic-like cells (MC3T3-E1 cells) cultured in a differentiation medium was significantly upregulated by the addition of PPDEs. Moreover, it was also clarified that the signaling pathway related to cytoplasmic calcium ions was activated by PPDEs. The mineralization of MC3T3-E1 cells has a similar trend with its gene expression and is synergistically enhanced by PPDEs with β-glycerophosphate. The biodistribution of fluorescence-labeled PPDEs was also determined after intravenous injection in mice. PPDEs accumulated well in the bone through the blood stream, whereas polyphosphotriesters (PPTEs) tended to be excreted from the kidneys. Hydrophilic PEP•Na showed a superior bone affinity as compared with PPP•Na. PPDEs could be candidate polymers for the restoration of bone remodeling and bone-targeting drug delivery platforms.

    DOI: 10.1002/jbm.a.37499

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  • Biodegradable Phosphocholine Cross‐Linker With Ion‐Pair Design for Tough Zwitterionic Hydrogel Reviewed

    Hoang Nam Nguyen, Thi Lan Huong Ngo, Yasuhiko Iwasaki, Chun-Jen Huang

    Advanced Materials Interfaces   2201002 - 2201002   2022.8

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Wiley  

    DOI: 10.1002/admi.202201002

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  • Nanofluidic Model Membrane for the Single-Molecule Observation of Membrane Proteins Reviewed

    Ryota Komatsu, Yasushi Tanimoto, Koji Ando, Kazuma Yasuhara, Yasuhiko Iwasaki, Fumio Hayashi, Kenichi Morigaki

    Langmuir   38 ( 23 )   7234 - 7243   2022.6

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    Publishing type:Research paper (scientific journal)   Publisher:American Chemical Society (ACS)  

    DOI: 10.1021/acs.langmuir.2c00724

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  • Headset bio-sniffer with wireless CMOS camera for percutaneous ethanol vapor from the ear canal Reviewed

    Takahiro Arakawa, Riki Ishikawa, Kenta Iitani, Koji Toma, Yasuhiko Iwasaki, Kohji Mitsubayashi

    Biosensors and Bioelectronics: X   100169 - 100169   2022.5

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Elsevier {BV}  

    DOI: 10.1016/j.biosx.2022.100169

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  • Evaluation of the long-term antibiofilm effect of a surface coating with dual functionality of antibacterial and protein-repellent effects Reviewed

    Pasiree THONGTHAI, Haruaki KITAGAWA, Susita NOREE, Yasuhiko IWASAKI, Yuhan LIU, Gabriela LARANJEIRA ABE, Satoshi YAMAGUCHI, Satoshi IMAZATO

    Dental Materials Journal   2022

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Japanese Society for Dental Materials and Devices  

    DOI: 10.4012/dmj.2021-205

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  • Dynamic in vitro hemocompatibility of oligoproline self-assembled monolayer surfaces Reviewed

    Aldona Mzyk, Gabriela Imbir, Yuri Noguchi, Marek Sanak, Roman Major, Justyna Wiecek, Przemyslaw Kurtyka, Hanna Plutecka, Klaudia Trembecka-Wójciga, Yasuhiko Iwasaki, Masato Ueda, Sachiro Kakinoki

    Biomaterials Science   2022

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1039/D2BM00885H

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  • External ears for non-invasive and stable monitoring of volatile organic compounds in human blood Reviewed International journal

    Koji Toma, Shota Suzuki, Takahiro Arakawa, Yasuhiko Iwasaki, Kohji Mitsubayashi

    Scientific Reports   11 ( 1 )   10415 - 10415   2021.12

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media {LLC}  

    <jats:title>Abstract</jats:title><jats:p>Volatile organic compounds (VOCs) released through skin (transcutaneous gas) has been increasing in importance for the continuous and real-time assessment of diseases or metabolisms. For stable monitoring of transcutaneous gas, finding a body part with little interference on the measurement is essential. In this study, we have investigated the possibility of external ears for stable and real-time measurement of ethanol vapour by developing a monitoring system that consisted with an over-ear gas collection cell and a biochemical gas sensor (bio-sniffer). The high sensitivity with the broad dynamic range (26 ppb–554 ppm), the high selectivity to ethanol, and the capability of the continuous measurement of the monitoring system uncovered three important characteristics of external ear-derived ethanol with alcohol intake for the first time: there is little interference from sweat glands to a sensor signal at the external ear; similar temporal change in ethanol concentration to that of breath with delayed peak time (avg. 13 min); relatively high concentration of ethanol relative to other parts of a body (external ear-derived ethanol:breath ethanol = 1:590). These features indicated the suitability of external ears for non-invasive monitoring of blood VOCs.</jats:p>

    DOI: 10.1038/s41598-021-90146-1

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  • pH-Responsive Association Behavior of Biocompatible Random Copolymers Containing Pendent Phosphorylcholine and Fatty Acid Reviewed

    Shin-ichi Yusa, Daishiro Oka, Yasuhiko Iwasaki, Kazuhiko Ishihara

    Langmuir   38 ( 17 )   5119 - 5127   2021.10

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:American Chemical Society ({ACS})  

    DOI: 10.1021/acs.langmuir.1c02200

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  • Immobilizing Bactericides on Dental Resins via Electron Beam Irradiation Reviewed

    P. Thongthai, H. Kitagawa, Y. Iwasaki, S. Noree, R. Kitagawa, S. Imazato

    Journal of Dental Research   100 ( 10 )   1055 - 1062   2021.9

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:{SAGE} Publications  

    Polymerizable bactericides, such as quaternary ammonium compound–based monomers, have been intensively studied as candidates for immobilizing antibacterial components on dental resin. However, they predominantly exhibit a bacteriostatic behavior, rather than bactericidal, as the immobilized components are left with insufficient molecular movement to disrupt the bacterial surface structure through contact-mediated action. In this study, we developed a novel strategy to increase the density of the immobilized bactericide and enhance its antibacterial/antibiofilm properties by combining a surface-grafting technique with electron beam irradiation. A solution of the quaternary ammonium compound–based monomer, 12-methacryloyloxydodecylpyridinium bromide (MDPB), was coated on polymethyl methacrylate (PMMA) resin specimens at the concentrations of 30, 50, and 80 wt%. The coated resins were subsequently exposed to 10 MeV of electron beam irradiation at 50 and 100 kGy, followed by thermal stabilization at 60 °C. The antibacterial effect was evaluated by inoculating a Streptococcus mutans suspension on the coated PMMA resin samples, which exhibited bactericidal effects even after 28 d of aging (P < 0.05, Tukey’s honestly significant difference test). Transmission electron microscopy and bacteriolytic activity evaluation revealed that the S. mutans cells had sustained membrane depolarization. Furthermore, the antibiofilm effects against S. mutans and bacteria collected from human saliva were assessed. The thickness and the percentage of membrane-intact cells of the S. mutans and multispecies biofilms formed on the MDPB-immobilized surfaces were significantly lower than the uncoated PMMA specimens, even after 28-d aging (P < 0.05, Tukey’s honestly significant difference test). Thus, the immobilization of antibacterial MDPB via electron beam irradiation induced rapid membrane depolarization, increasing membrane permeability and eventually causing cell death. Our strategy substantially enhances the antibacterial properties of the resinous materials and inhibits biofilm formation, therefore demonstrating significant potential for preventing infectious diseases in the oral environment.

    DOI: 10.1177/00220345211026569

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  • Lanoconazole-loaded emulsion stabilized with cellulose nanocrystals decorated with polyphosphoesters reduced inflammatory edema in a mouse model Reviewed

    Suphatra Hiranphinyophat, Akihisa Otaka, Syuji Fujii, Yasuhiko Iwasaki

    Polymer Journal   2021.8

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media {LLC}  

    DOI: 10.1038/s41428-021-00548-1

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  • Biochemical methanol gas sensor (Meoh bio-sniffer) for non-invasive assessment of intestinal flora from breath methanol Reviewed International journal

    Koji Toma, Kanako Iwasaki, Geng Zhang, Kenta Iitani, Takahiro Arakawa, Yasuhiko Iwasaki, Kohji Mitsubayashi

    Sensors   21 ( 14 )   4897 - 4897   2021.7

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:{MDPI} {AG}  

    Methanol (MeOH) in exhaled breath has potential for non-invasive assessment of intestinal flora. In this study, we have developed a biochemical gas sensor (bio-sniffer) for MeOH in the gas phase using fluorometry and a cascade reaction with two enzymes, alcohol oxidase (AOD) and formaldehyde dehydrogenase (FALDH). In the cascade reaction, oxidation of MeOH was initially catalyzed by AOD to produce formaldehyde, and then this formaldehyde was successively oxidized via FALDH catalysis together with reduction of oxidized form of β-nicotinamide adenine dinucleotide (NAD+). As a result of the cascade reaction, reduced form of NAD (NADH) was produced, and MeOH vapor was measured by detecting autofluorescence of NADH. In the development of the MeOH bio-sniffer, three conditions were optimized: selecting a suitable FALDH for better discrimination of MeOH from ethanol in the cascade reaction; buffer pH that maximizes the cascade reaction; and materials and methods to prevent leaking of NAD+ solution from an AOD-FALDH membrane. The dynamic range of the constructed MeOH bio-sniffer was 0.32–20 ppm, which encompassed the MeOH concentration in exhaled breath of healthy people. The measurement of exhaled breath of a healthy subject showed a similar sensorgram to the standard MeOH vapor. These results suggest that the MeOH bio-sniffer exploiting the cascade reaction will become a powerful tool for the non-invasive intestinal flora testing.

    DOI: 10.3390/s21144897

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  • Sensitive and selective methanol biosensor using two-enzyme cascade reaction and fluorometry for non-invasive assessment of intestinal bacteria activity. Reviewed International journal

    Koji Toma, Kanako Iwasaki, Takahiro Arakawa, Yasuhiko Iwasaki, Kohji Mitsubayashi

    Biosensors & bioelectronics   181   113136 - 113136   2021.6

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    For understanding the status of intestinal flora non-invasively, methanol (MeOH) has been attracting the attention. In this study, we have developed and compared two different liquid-phase methanol biosensors. One, referred to as the AOD electrosensor, utilized alcohol oxidase (AOD) and an oxygen electrode. It electrochemically measured the decrease in oxygen through AOD-catalyzed oxidation of MeOH. The other, referred to as the AOD-FALDH fluorosensor, exploited a cascade reaction of AOD and formaldehyde dehydrogenase (FALDH) in conjunction with a fiber-optic sensor. It measured increase in the fluorescence from reduced form of β-nicotinamide adenine dinucleotide (NADH) that was a final product of the two-enzyme cascade reaction. Due to the cascade reaction, the AOD-FALDH fluorosensor showed 3 times better sensitivity along with 335 times wider dynamic range (494 nM-100 mM) than those of the AOD electrosensor (1.5-300 μM). The selectivity to MeOH was also improved by the cascade reaction with AOD-FALDH as no sensor output was observed from other aliphatic alcohols than MeOH in contrast to the AOD electrosensor. Although the use of FALDH resulted in the increase in the sensor output from aldehydes, such as acetaldehyde and formaldehyde, considering their concentrations in body fluids, the influence on the sensor output is limited. These results indicate that incorporating the cascade reaction into fluorometry enables enhanced biosensing of MeOH that will be useful for assessment of intestinal flora with little burden.

    DOI: 10.1016/j.bios.2021.113136

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  • Long-lasting hydrophilic surface generated on poly(dimethyl siloxane) with photoreactive zwitterionic polymers Reviewed International journal

    Hiroki Nakano, Sachiro Kakinoki, Yasuhiko Iwasaki

    Colloids and Surfaces B: Biointerfaces   205   111900 - 111900   2021.6

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Elsevier {BV}  

    Poly(dimethylsiloxane) (PDMS) is known as one of the most established polymers for making elastomers. Therefore, it is commonly used for the fabrication of biomedical devices. Many PDMS surface modification processes have been proposed recently to increase PDMS reliability in medical fields. However, the modified surface's long-term stability is still limited. Hydrophobic recovery of PDMS is widely recognized as a factor that reduces the efficacy of PDMS surface modification. The photoreactive zwitterionic polymer effectively suppresses the hydrophobic recovery of PDMS, according to the current analysis. The photoreactive zwitterionic monomer, 2-[2-(Methacryloyloxy)ethyldimethylanmmonium] ethyl benzophenoxy phosphate (MBPP) was polymerized by conventional radical polymerization and coated on O2-plasma-treated PDMS specimens. The specimens were immersed in an aqueous solution of 2-methacryloyloxyethyl phosphorylcholine (MPC) and exposed under ultraviolet (UV) radiation for 3 h. Instead, of poly(MBPP) (PMBPP), benzophenone (BP) was also used as a conventional photoinitiator. The time-dependent change in the wettability and elemental composition of the specimen surface was monitored for nine weeks after photo-grafting of poly[2-methacryloyloxyethyl phosphorylcholine (MPC)] (PMPC). The advancing and receding contact angles (θA/θR) of the pristine PDMS specimen were 112°/71° and significantly decreased immediately after the grafting of PMPC regardless of types of photoinitiator. However, the hydrophobicity of the surface gradually recovered, and θA was changed from 12° to 81° for nine weeks of storage under air atmosphere when BP was used as a photoinitiator for graft polymerization of MPC. However, surface hydrophilicity (θA ≅ 20°) of the surface grafted with PMPC with PMBPP as an initiator was effectively preserved for nine weeks. This surface also showed excellent lubricity and non-fouling properties regardless of the storage periods. Therefore, zwitterionic photoreactive polymer, PMBPP, is then used as a macrophotoinitiator for the surface modification of PDMS.

    DOI: 10.1016/j.colsurfb.2021.111900

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  • Control of Structural Coloration by Natural Sunlight Irradiation on a Melanin Precursor Polymer Inspired by Skin Tanning. Reviewed International journal

    Taku Okoshi, Takeshi Iwasaki, Shimon Takahashi, Yasuhiko Iwasaki, Keiki Kishikawa, Michinari Kohri

    Biomacromolecules   22 ( 4 )   1730 - 1738   2021.4

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    Natural melanin affects the reflection and absorption of light, and it is known as an important element in producing bright structural colors in nature. In this study, we prepared core-shell particles using a melanin precursor polymer, that is, polytyrosine (PTy), as a shell layer by the oxidative polymerization of tyrosine ethyl ester (Ty) in the presence of cerium oxide (CeO2) core particles. Inspired by skin tanning, irradiating the CeO2@PTy core-shell particles with UV or natural sunlight caused melanization by extending the π-conjugated length of PTy, producing colloidal particles with the ability to absorb light. The pellet samples consisting of CeO2@PTy particles appeared whitish because of multiple scattered light. In contrast, the light absorption capacity of CeO2@PTy UV or CeO2@PTy Sun particles after light irradiation suppressed scattered light, dramatically improving the visibility of the structural color of the pellet samples made from these particles. Thus, a new method has been developed to control the visualization of structural colors to the human eye by irradiating the melanin precursor polymer with light.

    DOI: 10.1021/acs.biomac.1c00161

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  • Controlled biointerfaces with biomimetic phosphorus-containing polymers Invited Reviewed International journal

    Suphatra Hiranphinyophat, Yasuhiko Iwasaki

    Science and Technology of Advanced Materials   22 ( 1 )   301 - 316   2021.3

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    Phosphorus is a ubiquitous and one of the most common elements found in living organisms. Almost all molecules containing phosphorus in our body exist as analogs of phosphate salts or phosphoesters. Their functions are versatile and important, being responsible for forming the genetic code, cell membrane, and mineral components of hard tissue. Several materials inspired from these phosphorus-containing biomolecules have been recently developed. These materials have shown unique properties at the biointerface, such as nonfouling ability, blood compatibility, lubricity, mineralization induction capability, and bone affinity. Several unfavorable events occur at the interface of materials and living organisms because most of these materials have not been designed while taking host responses into account. These unfavorable events are directly linked to reducing functions and shorten the usable periods of medical devices. Biomimetic phosphorus-containing polymers can improve the reliability of materials in biological systems. In addition, phosphorus-containing biomimetic polymers are useful not only for improving the biocompatibility of material surfaces but also for adding new functions due to the flexibility in molecular design. In this review, we describe the recent advances in the control of biointerfacial phenomena with phosphorus-containing polymers. We especially focus on zwitterioninc phosphorylcholine polymers and polyphosphoesters.

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  • Enhancement of osteoblast differentiation using poly(ethylene sodium phosphate) Reviewed

    Akihisa Otaka, Kenjiro Kiyono, Yasuhiko Iwasaki

    Materialia   15   100977 - 100977   2021.3

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    Biodegradable polyphosphoesters (PPEs) are of increasing interest due to their promising biomedical applications. Polyphosphodiesters (PPDEs), formed by polyphosphotriester (PPTE) dealkylation, have bone-targeting properties in vivo and therefore are promising polymer drug candidates for bone disease treatment. However, their effects on osteoblasts are still unclear. This study prepared two polymer structures, poly(methyl ethylene phosphate) (PMP) and poly(ethylene sodium phosphate) (PEP•Na), as PPTE and PPDE models, respectively, and investigated their effects on mouse osteoblastic cell (MC3T3-E1) differentiation. Results showed that PMP is inert toward osteoblast differentiation. In contrast, PEP•Na enhanced alkaline phosphatase (ALP) synthesis, matrix mineralization, and osteoblast-related gene expression. PEP•Na also enhanced Wnt signaling pathway–dependent Alp expression, in addition to its own internalization into the cytosol during 3 days of differentiation culture. These results showed that dealkylated PPEs are a polymer drug candidate for osteoporosis treatment, not only because of their bone-targeting properties but also because of the controllable effects of bone anabolism via osteoblast differentiation enhancement.

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  • Dual-target gas-phase biosensor (bio-sniffer) for assessment of lipid metabolism from breath acetone and isopropanol Reviewed

    Koji Toma, Masato Tsujii, Takahiro Arakawa, Yasuhiko Iwasaki, Kohji Mitsubayashi

    Sensors and Actuators B: Chemical   329   129260 - 129260   2020.12

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    Volatile organic compounds (VOCs) in breath and skin gas are promising samples for non-invasive and simple disease screening and metabolism assessment. In addition, simultaneous measurement of multiple VOCs helps to improve the examination quality and allows for more reliable disease screening and investigation of detailed metabolic pathways. In this study, we have developed a dual-target gas-phase biosensor (bio-sniffer) that allows for measurement of isopropanol (IPA) and acetone vapours, relevant VOCs for lipid metabolisms, by simply exchanging coenzyme solutions. The measurement exploited a reversible redox reaction that was catalysed by secondary alcohol dehydrogenase (S-ADH). IPA/acetone was oxidised/reduced together with reduction/oxidation of a coenzyme, oxidised (NAD+)/reduced (NADH) form of β-nicotinamide adenine dinucleotide, depending on surrounding pH (8.5/7.5). This reaction resulted in producing/consuming NADH which exhibited autofluorescence (λex = 340 nm, λfl = 490 nm), by which IPA/acetone was measured. The characterization of the dual-target bio-sniffer showed the dynamic ranges for IPA and acetone vapour were 3.3–1000 ppb and 13.0–3000 ppb, respectively, which encompasses those in the breath of healthy people (IPA, 10–30 ppb; acetone, 200–900 ppb). Finally, the dual-target bio-sniffer was applied for measurement of IPA and acetone in the breath of healthy people. As with the standard IPA and acetone vapour, intermittent and repeated measurement of both VOCs in the breath was demonstrated. These results indicated that the dual-target bio-sniffer would be a useful tool to assess the lipid metabolism in detail by measuring temporal changes of IPA and acetone concentrations in the breath.

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  • Ultra-Sensitive Isopropanol Biochemical Gas Sensor (Bio-Sniffer) for Monitoring of Human Volatiles Reviewed International journal

    Po-Jen Chien, Takuma Suzuki, Ming Ye, Koji Toma, Takahiro Arakawa, Yasuhiko Iwasaki, Kohji Mitsubayashi

    Sensors   20 ( 23 )   6827 - 6827   2020.11

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    <jats:p>Our groups have previously developed a biochemical gas sensor to measure isopropanol (IPA) in exhaled air and have applied it for breath IPA investigation in healthy subjects and diabetes patients. In this study, the original bio-sniffer was modified with a series of components that improved the limit of detection (LOD). First, the modified IPA bio-sniffer used a C8855-type photomultiplier tube (PMT) that performed well in the photon sensitivity at the peak wavelength of nicotinamide adenine dinucleotide (NADH) fluorescence. Second, the multi-core bifurcated optical fiber, which incorporated 36 fibers to replace the previous dual-core type, enhanced the fluorescence collection. Third, the optical fiber probe was reinforced for greater width, and the flow-cell was redesigned to increase the area of the enzyme-immobilized membrane in contact with the air sample. These modifications lowered the detection limit to 0.5 ppb, a significant increase over the previous 1.0 ppb. Moreover, the modified bio-sniffer successfully analyzed the IPA concentration in exhaled air from a volunteer, which confirmed its capability for real-world sample detection. The modified bio-sniffer is more applicable to breath measurement and the detection of other extremely-low-concentration samples.</jats:p>

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  • Particle-stabilized oil-in-water emulsions as a platform for topical lipophilic drug delivery Reviewed International journal

    Suphatra Hiranphinyophat, Akihisa Otaka, Yuta Asaumi, Syuji Fujii, Yasuhiko Iwasaki

    Colloids and Surfaces B: Biointerfaces   197   111423 - 111423   2020.10

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    Low-environmental-impact emulsion systems for transdermal drug delivery in topical treatment have gained increasing interest. However, low stability and adverse systemic side effects severely decrease their efficiency. This study proposed a stable oil-in-water (O/W) emulsion loaded with bifonazole (BFZ) as a lipophilic drug stabilized by poly(2-isopropoxy-2-oxo-1,3,2-dioxaphospholane)-modified cellulose nanocrystals (CNC-g-PIPP) as vehicles for topical delivery of lipophilic drugs. We fully characterized stability, BFZ-loaded particle-stabilized emulsions (PEs) for morphology, droplet size, and its distribution. In addition, we evaluated the in vitro drug-releasing capacity and in vitro skin permeation of BFZ in a porcine skin animal model using a side-bi-side® diffusion cell. An O/W BFZ-loaded emulsion stabilized with CNC-g-PIPP particles (BFZ-loaded CP-PE) with a small mean droplet size of 2.54 ± 1.39 μm was developed and was stable for > = 15 days without a significant change in droplet size. The BFZ-loading efficiency in PEs was 83.1 %. BFZ was slowly released over an extended period, and the releasing ratio from BFZ-loaded CP-PE was only 17 % after 48 h. The BFZ-loaded CP-PE showed a ∼4.4-fold increase in BFZ permeation and penetration compared to a conventional surfactant-stabilized emulsion and BFZ control solution. Fluorescence-labeling studies showed that BFZ-loaded CP-PE could well penetrate skin layers from the stratum corneum (SC) to the dermis. In addition, histopathology studies of porcine skin treated with the PE formulation showed an intact SC with unaltered adjacent structures and no observed signs of inflammation. Therefore, the proposed CP-PE shows great potential as a transdermal drug carrier for enhancing lipophilic drug permeation.

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  • Bone Mineral Affinity of Polyphosphodiesters Invited Reviewed International journal

    Yasuhiko Iwasaki

    Molecules   25 ( 3 )   2020.2

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    Biomimetic molecular design is a promising approach for generating functional biomaterials such as cell membrane mimetic blood-compatible surfaces, mussel-inspired bioadhesives, and calcium phosphate cements for bone regeneration. Polyphosphoesters (PPEs) are candidate biomimetic polymer biomaterials that are of interest due to their biocompatibility, biodegradability, and structural similarity to nucleic acids. While studies on the synthesis of PPEs began in the 1970s, the scope of their use as biomaterials has increased in the last 20 years. One advantageous property of PPEs is their molecular diversity due to the presence of multivalent phosphorus in their backbones, which allows their physicochemical and biointerfacial properties to be easily controlled to produce the desired molecular platforms for functional biomaterials. Polyphosphodiesters (PPDEs) are analogs of PPEs that have recently attracted interest due to their strong affinity for biominerals. This review describes the fundamental properties of PPDEs and recent research in the field of macromolecular bone therapeutics.

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  • Front cover

    Yasuhiko Iwasaki

    Chemical Communications   2020

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    DOI: 10.1039/d0cc90215b

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  • Protein patterning with antifouling polymer gel platforms generated using visible light irradiation Reviewed International journal

    Yasuhiko Iwasaki

    Chemical Communications   56 ( 41 )   5472 - 5475   2020

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    <p>Visible light-assisted protein patterning on a solid surface was performed with phosphorylcholine (PC) polymers bearing tyrosine residues. Because of the antifouling nature of PC polymers, protein immobilisation was regiospecifically controlled...</p>

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  • Bone-targeting phospholipid polymers to solubilize the lipophilic anticancer drug Reviewed International journal

    Otaka, A., Yamaguchi, T., Saisho, R., Hiraga, T., Iwasaki, Y.

    Journal of Biomedical Materials Research - Part A   108 ( 10 )   2090 - 2099   2020

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    Current chemotherapy methods have limited effectiveness in eliminating bone metastasis, which leads to a poor prognosis associated with severe bone disorders. To provide regional chemotherapy for this metastatic tumor, a bone-targeting drug carrier was produced by introducing the osteotropic bisphosphonate alendronate (ALN) units into an amphiphilic phospholipid polymer, poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate). The polymer can form nanoparticles with a diameter of less than 30 nm; ALN units were exposed to the outer layer of the particle. A simple mixing procedure was used to encapsulate a hydrophobic anticancer drug, known as docetaxel (DTX), in the polymer nanoparticle, providing a uniform solution of a polymer-DTX complex in the aqueous phase. The complex showed anticancer activities against several breast cancer cell lines, and the complex formation did not hamper the pharmacological effect of DTX. The fluorescence observations evaluated by an in vivo imaging system and fluorescence microscopy showed that the addition of ALN to the polymer-DTX complex enhanced bone accumulation. Bone-targeting phospholipid polymers are potential solubilizing excipients used to formulate DTX and deliver the hydrophobic drug to bone tissues by blood administration.

    DOI: 10.1002/jbm.a.36968

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  • Surfaces immobilized with oligo-prolines prevent protein adsorption and cell adhesion Reviewed International journal

    Yasuhiko Iwasaki

    Journal of Materials Chemistry B   8 ( 11 )   2233 - 2237   2020

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    <p>In this study, oligo-prolines, (Pro)n (n=6 and 9) inspired by the backbone structure of collagen, were evaluated as a novel non-ionic anti-fouling peptide. Two oligo-prolines with a cysteine residue were...</p>

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  • Development of novel surface coating composed of MDPB and MPC with dual functionality of antibacterial activity and protein repellency Reviewed International journal

    Thongthai, P., Kitagawa, H., Kitagawa, R., Hirose, N., Noree, S., Iwasaki, Y., Imazato, S.

    Journal of Biomedical Materials Research - Part B Applied Biomaterials   108 ( 8 )   3241 - 3249   2020

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    Resin-based reconstructive/restorative materials with antibacterial effects are potentially useful for preventing dental and oral diseases. To this end, the immobilization of an antibacterial component on the surface of a resin by incorporating polymerizable bactericide such as a quaternary ammonium compound-monomer 12-methacryloyloxydodecylpyridinium bromide (MDPB) is an effective technique. However, the effectiveness of immobilized bactericide is reduced by salivary protein coverage. We address this issue by utilizing 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer, which exhibits protein repellency, with MDPB to fabricate a novel copolymer, which served as a surface coating on a methacrylate-based resin. This coating provided a more hydrophilic surface than that provided by MDPB coating and reduced the adsorption of bovine serum albumin and salivary protein. To evaluate bacterial growth on the contact surface, Streptococcus mutans suspension was placed on the coated specimen. After 24-h incubation, MDPB/MPC copolymer exhibited killing effects against S. mutans. Moreover, confocal laser scanning microscopy and scanning electron microscopy were used to evaluate biofilm formation after 48-h incubation in S. mutans suspension, which revealed sparse biofilm and dead bacteria in biofilm on the surface coated with MDPB/MPC. Overall, the proposed surface coating on dental resins exhibited protein-repellent ability and inhibitory effects against bacteria and oral biofilms.

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  • Skin ethanol gas measurement system with a biochemical gas sensor and gas concentrator toward monitoring of blood volatile compounds Reviewed International journal

    Arakawa, T., Aota, T., Iitani, K., Toma, K., Iwasaki, Y., Mitsubayashi, K.

    Talanta   219   121187 - 121187   2020

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    © 2020 Elsevier B.V. We developed a biochemical gas sensor (bio-sniffer) using the enzymatic reaction of alcohol dehydrogenase (ADH) to target ethanol in skin gas. By introducing a gas concentrator using liquid nitrogen, we constructed a highly sensitive system for skin gas measurements. The ethanol bio-sniffer was built from an optical-fiber probe employing an ADH enzyme membrane, an UV-LED light source for excitation, and a photomultiplier tube. Ethanol was measured by detecting the autofluorescence of the coenzyme NADH due to the enzymatic reaction of ADH. We established a system for measuring concentrated gases by connecting the sensor with a gas concentrator and introducing concentrated skin gas to the sensing surface. This suppressed diffusion of the concentrated gases to achieve maximum fluorescence intensity by optimizing the measurement system. The calibration curve from obtained peak values showed ethanol gas can be measured over 1–3100 ppb, which included skin gas concentrations during alcohol consumption. Finally, when applied to measurements of ethanol in skin gas following alcohol consumption, the output was found to be dependent on concentration, similarly to using standard gases. Consecutive measurements were possible using periodic sampling with 6-min intervals for 180 min of monitoring. Skin ethanol concentrations rose from 20 min after consuming the alcohol, exhibited a peak value of 25 ppb skin gas ethanol at around 60 min, and gradually declined. Thus, the system can be used for non-invasive percutaneous evaluation of human volatile organic chemicals in blood.

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  • Highly Durable Lubricity of Photo-Cross-Linked Zwitterionic Polymer Brushes Supported by Poly(ether ether ketone) Substrate

    Hiroki Nakano, Yuri Noguchi, Sachiro Kakinoki, Mai Yamakawa, Issey Osaka, Yasuhiko Iwasaki

    ACS Applied Bio Materials   2020

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    For improving lubricity, the formation of zwitterionic polymer brushes on material surfaces is one of the most promising approaches. In this study, the photoreactive zwitterionic monomer 2-[2-(methacryloyloxy)ethyldimethylanmmonium] ethyl benzophenoxy phosphate (MBPP) was synthesized to improve the stability of zwitterionic polymer brushes. Although MBPP contains a benzophenone moiety in this molecule, it is water-soluble because of the zwitterionic linker. As a substrate, poly(ether ether ketone) (PEEK) was selected because it has recently been used to replace metals in orthopedic implants. Furthermore, PEEK is photosensitive, and UV graft polymerization of (meth)acrylic monomers on the surface can be performed without using any photoinitiators. Aqueous solutions containing various molar ratios of 2-(methacryloyloxy)ethyl phosphorylcholine (MPC) and MBPP were prepared, and the PEEK specimens were immersed in these solutions. UV light was used to irradiate the solutions for 180 min, and the formation of grafting layers of zwitterionic polymers on PEEK specimens was confirmed using contact angle measurement and X-ray photoelectron spectroscopy. The surface friction of PEEK was effectively reduced via the photopolymerization of zwitterionic monomers. However, the surface lubricity of poly(MPC) (PMPC)-grafted surface deteriorated during continuous friction because of the removal of PMPC from the surface. Nevertheless, the stability of polymer brushes was effectively improved by adding only 0.5-0.75 mol % of MBPP in the monomer solution. Moreover, the reduction of wear on the surface was determined using confocal laser microscopy. The excellent lubrication phenomenon was attributed to preserving the hydration state of grafted polymers under compressive stress. Moreover, bacterial adhesion on substrates was tested and observed on a neat PEEK and scratched regions of uncross-linked PMPC-grafted PEEK. Note that bacterial adhesion was completely suppressed on the surface of PEEK modified with cross-linked PMPC brushes with MBPP. Thus, we conclude that the surface modification of PEEK with MPC and MBPP can provide ideal surface properties for orthopedic devices.

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  • Reduction of acidic erosion and oral bacterial adhesion through the immobilization of zwitterionic polyphosphoesters on mineral substrates Reviewed

    Yasuhiko Iwasaki

    Chemistry Letters   2019.10

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    DOI: 10.1246/cl.190709

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  • Surface Grafting Polyphosphoesters on Cellulose Nanocrystals To Improve the Emulsification Efficacy Reviewed International journal

    Suphatra Hiranphinyophat, Yuta Asaumi, Syuji Fujii, Yasuhiko Iwasaki

    Langmuir   35 ( 35 )   11443 - 11451   2019.9

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    Particle-stabilized emulsion systems have been developed to address the problematic properties of conventional surfactants. However, the nature and properties of the fine particles used in such systems remain a critical issue for stability enhancement. Herein, we describe a thermoswitchable oil-in-water (O/W) particle-stabilized emulsion that exhibits improved stability due to the addition of cellulose nanocrystals (CNCs) modified with poly[2-isopropoxy-2-oxo-1,3,2-dioxaphospholane] (PIPP), which exhibits relatively good biocompatibility and biodegradability. Various parameters, such as surface activity, concentration of particles, polarity of solvents, and temperatures, on the formation of emulsions with CNCs grafted with PIPP (CNC-g-PIPP) were investigated. Results showed that the surface activity of CNC-g-PIPP was significantly improved compared with the unmodified material. Heptane-in-water particle-stabilized emulsions with CNC-g-PIPP were stably formed, and the effect of temperature on the stability of the emulsions was characterized. CNC-g-PIPP exhibited function as an effective particulate emulsifier at 4 °C because of the strong adsorption at the oil-water interface. However, the emulsions rapidly disintegrated at 45 °C, which is above the low critical solution temperature of PIPP on CNC, as the hydrophobized CNC-g-PIPP desorbed from the oil-water interface. Based on these findings, a thermally induced reversible emulsification/demulsification was presented. The resulting switchable particle-stabilized emulsion based on CNC-g-PIPP shows promise for the ability to control the stability of an emulsion in response to temperature, which is attractive for use in biological applications.

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  • Clickable Zwitterionic Copolymer as a Universal Biofilm‐Resistant Coating Reviewed

    Yasuhiko Iwasaki

    Macromolecular Materials and Engineering   2019.7

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    DOI: 10.1002/mame.201900286

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  • Immobilization of polyphosphoesters on poly(ether ether ketone) (PEEK) for facilitating mineral coating Reviewed International journal

    Yasuhiko Iwasaki

    Journal of Biomaterials Science, Polymer Edition   30 ( 10 )   861 - 876   2019.7

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    Poly(ether ether ketone) (PEEK) is an alternative material to metals for orthopedic applications. However, the compatibility of PEEK with hard tissues needs to be improved. To address this issue, this study proposes a novel technique for PEEK surface modifications. A polyphosphodiester macromonomer (PEPMA·Na) was synthesized via the demethylation of polyphosphotriester macromonomer obtained via the ring-opening polymerization of cyclic phosphoesters using 2-hydroxypropyl methacrylamide as the initiator. The surface modification of PEEK was performed via photoinduced and self-initiated graft polymerization of PEPMA·Na without using any photoinitiators. The amount of phosphorus due to poly(PEPMA·Na) immobilized on PEEK increased with an increase in the photoirradiation time. The PEEK surface turned hydrophilic due to poly(PEPMA·Na) grafting, with almost similar advancing and receding contact angles, implying that the modified PEEK surface (PEEK-g-poly(PEPMA·Na)) was homogeneous. Specimens were mineral coated by simple static soaking in ×1.5 simulated body fluid (1.5SBF) and by an alternative process that included additional soaking steps in 200 mM CaCl2 aq. and 200 mM K2HPO4 aq. before static soaking in 1.5SBF. Specimens were immersed in 1.5SBF for 28 days in simple static soaking, after which the PEEK-g-poly(PEPMA·Na) surface was completely covered with spherical cauliflower-like mineral deposits that resembled octacalcium phosphate (OCP). Their structural similarities were confirmed via X-ray diffraction (XRD), energy dispersive X-ray spectrometry (EDS), and X-ray fluorescence (XRF) analyses. However, these mineral deposits were not observed on the bare PEEK surface. Due to the additional soaking steps (alternative soaking) undertaken before the static soaking of the specimens in 1.5SBF, the mineral coating on the PEEK-g-poly(PEPMA·Na) was dramatically accelerated and the surface was fully covered with mineral deposits in only one day of soaking. The mineral deposits resulting from both the soaking processes had similar structures. Compared with bare PEEK, osteoblastic MC3T3-E1 cells proliferated more actively on mineral-coated PEEK-g-poly(PEPMA·Na). Thus, the surface immobilization of poly(PEPMA·Na) on a PEEK surface is effective for mineral coating and may be useful to provide hard-tissue compatibility on PEEK.

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  • Endocytosis of poly(ethylene sodium phosphate) by macrophages and the effect of polymer length on cellular uptake Reviewed

    Yasuhiko Iwasaki

    Journal of Industrial and Engineering Chemistry   2019.7

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  • Thermally Assisted Generation of Protein–Poly(ethylene sodium phosphate) Conjugates with High Mineral Affinity Reviewed International journal

    Susita Noree, Yasuhiko Iwasaki

    ACS Omega   4 ( 2 )   3398 - 3404   2019.2

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    Protein therapeutics has recently attracted interest in various medical treatments. However, the structure and function preservation in proteins under physiological conditions is still an important issue and reliable immobilization techniques are required. In this study, the thermally assisted complexation of proteins with amphiphilic polyphosphoesters is proposed as a new methodology for their durability improvement. Amphiphilic cholesterol-terminated poly(ethylene sodium phosphate) (CH-PEP·Na) was synthesized via the organocatalytic ring-opening polymerization of 2-methoxy-2-oxo-1,3,2-dioxaphospholane initiated by cholesterol as the hydrophobic molecule and followed by demethylation and neutralization. For the protein nanocarrier preparation, a complex of the amphiphilic CH-PEP·Na with bovine serum albumin (BSA) was formed through the hydrophobic interactions between the lipophilic moieties of the protein and the cholesteryl groups of the CH-PEP·Na chains, which were induced by thermal treatment at 90 °C. The resulting complex size ranged between 27 and 51 nm, as confirmed by dynamic light scattering. The complexes dispersed in an aqueous medium exhibited a high stability in size for up to 1 month of storage. CH-PEP·Na efficiently inhibited the thermal aggregation and sedimentation of BSA, unlike poly(ethylene sodium phosphate) (PEP·Na) and cholesterol-terminated poly(ethylene glycol) (CH-PEG). In addition, CH-PEP·Na was able to protect the complexed BSA against proteolytic digestion and the BSA-CH-PEP·Na complexes well adsorbed onto hydroxyapatite even in the presence of BSA (5.5 g/dL). Hence, thermally induced protein-CH-PEP·Na complexes can be a potential tool for the development of bone and dental applications.

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  • Label-Free Specific Detection and Collection of C-Reactive Protein Using Zwitterionic Phosphorylcholine-Polymer-Protected Magnetic Nanoparticles Reviewed

    Sana Iwasaki, Hideya Kawasaki, Yasuhiko Iwasaki

    Langmuir   2019.2

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    DOI: 10.1021/acs.langmuir.8b01007

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  • Cardiac differentiation of induced pluripotent stem cells on elastin-like protein-based hydrogels presenting a single-cell adhesion sequence Reviewed

    Kambe, Yusuke, Tokushige, Takayuki, Mahara, Atsushi, Iwasaki, Yasuhiko, Yamaoka, Tetsuji

    Polymer Journal   51 ( 1 )   2019

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  • Zwitterionic Interfaces: Concepts and Emerging Applications Special Issue. Reviewed International journal

    Jiang, Shaoyi, Ishihara, Kazuhiko, Iwasaki, Yasuhiko, Vancso, Julius

    Langmuir : the ACS journal of surfaces and colloids   35 ( 5 )   1055 - 1055   2019

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  • 骨親和性ポリリン酸エステルと破骨細胞との相互作用

    岩崎 泰彦, 大高 晋之, 中村 美穂, 横田 淳司, 根尾 昌志

    日本バイオマテリアル学会大会予稿集   40回   101 - 101   2018.11

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  • シンバスタチン添加α-TCP微粒子エマルション骨ペーストの特性評価および骨形成効果

    舘山 彰人, 加藤 昭人, 宮治 裕史, 西田 絵利香, 岩崎 泰彦, 藤井 秀司, 川本 康平, 蔀 佳奈子, 降籏 友和, 眞弓 佳代子, 菅谷 勉

    日本歯周病学会会誌   60 ( 秋季特別 )   119 - 119   2018.10

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  • Call for Papers for Zwitterionic Interfaces: Concepts and Emerging Applications Reviewed International journal

    Jiang, Shaoyi, Ishihara, Kazuhiko, Iwasaki, Yasuhiko, Vancso, Julius, MacLaughlin, Christina

    Langmuir   34 ( 11 )   3375 - 3375   2018

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    DOI: 10.1021/acs.langmuir.8b00563

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  • Bone-targeting poly(ethylene sodium phosphate) Reviewed

    Yasuhiko Iwasaki, Atsushi Yokota, Akihisa Otaka, Naoyuki Inoue, Akane Yamaguchi, Toru Yoshitomi, Keitaro Yoshimoto, Masashi Neo

    Biomaterials Science   2018

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    DOI: 10.1039/C7BM00930E

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  • Real-time monitoring of skin ethanol gas by a high-sensitivity gas phase biosensor (bio-sniffer) for the non-invasive evaluation of volatile blood compounds. Reviewed

    Arakawa, Takahiro, Suzuki, Takuma, Tsujii, Masato, Iitani, Kenta, Chien, Po-Jen, Ye, Ming, Toma, Koji, Iwasaki, Yasuhiko, Mitsubayashi, Kohji

    Biosensors & bioelectronics   2018

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  • Bone induction by α-tricalcium phosphate microparticle emulsion containing simvastatin Reviewed

    Akito Tateyama, Akihito Kato, Hirofumi Miyaji, Erika Nishida, Yasuhiko Iwasaki, Syuji Fujii, Kohei Kawamoto, Kanako Shitomi, Tomokazu Furihata, Kayoko Mayumi, Tsutomu Sugaya

    Nano Biomedicine   9 ( 2 )   69 - 76   2018

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    To improve the degradability and operability of conventional bone graft materials, we fabricated a water-oil emulsion based on α-tricalcium phosphate (α-TCP) bone paste. Simvastatin, a lipophilic hyperlipidemia treatment agent, reportedly enhances the expression of bone morphogenetic protein- 2 and subsequent bone formation. Accordingly, we assessed the bone forming effects of α-TCP bone-paste containing simvastatin in rat cranial bone defects. Bone paste exhibited porous structure and generation of hydroxyapatite after solidification. X-ray image analysis and histological examination were carried out after implantation of bone paste into rat skull defect. The results showed that new bone was formed after implantation of bone paste containing simvastatin. In particular, bone volume in the 0.1 mg simvastatin group was significantly promoted when compared to controls (no implantation). No bone paste residue was observed in the bone defect at 4 weeks after surgery. Therefore, α-TCP bone paste containing simvastatin is degradable and beneficial for bone tissue engineering.

    DOI: 10.11344/nano.9.69

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  • Polymer coating glass to improve the protein antifouling effect Reviewed

    Honda, Tomoko, Nakao, Aiko, Ishihara, Kazuhiko, Higaki, Yuji, Higaki, Keiko, Takahara, Atsushi, Iwasaki, Yasuhiko, Yusa, Shin-ichi

    Polymer Journal   50 ( 5 )   2018

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    DOI: 10.1038/s41428-018-0026-x

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  • Fiber-optic bio-sniffer (biochemical gas sensor) using reverse reaction of alcohol dehydrogenase for exhaled acetaldehyde. Reviewed

    Iitani, Kenta, Chien, Po-Jen, Suzuki, Takuma, Toma, Koji, Arakawa, Takahiro, Iwasaki, Yasuhiko, Mitsubayashi, Kohji

    ACS sensors   2018

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    DOI: 10.1021/acssensors.7b00865

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  • Bone-targeting polyphosphoesters and their interaction with bone cells Reviewed

    Iwasaki, Yasuhiko, Yokota, Atsushi, Otaka, Akihisa, Neo, Masashi

    Abstracts of Papers of the American Chemical Society   256   2018

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  • Surface Modification of Macrophages with Nucleic Acid Aptamers for Enhancing the Immune Response against Tumor Cells. Reviewed International journal

    Sugimoto, Shunsuke, Iwasaki, Yasuhiko

    Bioconjugate chemistry   29 ( 12 )   4160 - 4167   2018

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    Antigen-presenting cells play a dominant role in cancer immunotherapy. Tumor cells, however, can still resort to several mechanisms of immune evasion that ultimately lead to the development of tumor tissues. In the current study, we performed surface modification of live macrophages with nucleic acid aptamers with the aim to enhance their affinity for tumor cells. Intercellular adhesion of tumor cells to surface-modified macrophages and the functions of the macrophages when in contact with tumor cells were investigated. To immobilize thiol-terminated nucleic acid aptamers that showed high affinity for the membrane protein of the tumor cells, methacryloyl groups were delivered into the sialic acids of the macrophages via metabolic glycoengineering (MGE). The proposed surface modification was cytocompatible and did not induce any undesirable activation of macrophages. According to the cell proliferation assay, the density of aptamers immobilized on a macrophage was found to decrease over time. However, the presence of aptamers on the cell surface was observed for more than 24 h after the immobilization. The number of adherent tumor cells on aptamer-immobilized macrophages was significantly larger than that of non-immobilized macrophages. Although the number of adherent tumor cells on aptamer-immobilized macrophages was not influenced by the pretreatment of doxorubicin to induce apoptosis in tumor cells, the apoptosis-induced tumor cells were highly phagocytosed by the aptamer-immobilized macrophages. The secretion amount of proinflammatory cytokines (TNF-α and IL-12) from the macrophages was coincident with the phagocytic index, which increased with the phagocytic uptake of tumor cells by the macrophages. In addition, the expression level of the major histocompatibility complex (MHC) class I and II molecules, required for antigen presentation, increased in nucleic acid aptamer-immobilized macrophages. Overall, the surface modification of macrophages with nucleic acid aptamers improved the tumor cell recognition of macrophages, indicating that the combination of cell surface engineering and anticancer drug treatment could constitute a promising strategy for tumor cell elimination.

    DOI: 10.1021/acs.bioconjchem.8b00793

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  • ポリリン酸エステルによるインテリジェントバイオマテリアルの創出 Reviewed

    岩崎泰彦

    高分子論文集   74:172-181   2017.3

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  • Well-defined protein immobilization on photo-responsive phosphorylcholine polymer surfaces. Reviewed

    Tanaka, Masako, Kawai, Shugo, Iwasaki, Yasuhiko

    Journal of biomaterials science. Polymer edition   2017

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    DOI: 10.1080/09205063.2017.1366251

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  • Bone-specific poly(ethylene sodium phosphate) -bearing biodegradable nanoparticles Reviewed

    Hirano, Yuya, Iwasaki, Yasuhiko

    Colloids and Surfaces B-Biointerfaces   153   2017

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    DOI: 10.1016/j.colsurfb.2017.02.015

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  • Hybrid model membrane combining micropatterned lipid bilayer and hydrophilic polymer brush Reviewed

    Morigaki, Kenichi, Nishimura, Toshiki, Tamura, Fuyuko, Tanimoto, Yasushi, Ando, Koji, Sudo, Yuki, Hayashi, Fumio, Iwasaki, Yasuhiko

    Abstracts of Papers of the American Chemical Society   253   2017

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  • Biochemical Gas Sensors (Biosniffers) Using Forward and Reverse Reactions of Secondary Alcohol Dehydrogenase for Breath Isopropanol and Acetone as Potential Volatile Biomarkers of Diabetes Mellitus Reviewed

    Chien, Po-Jen, Suzuki, Takuma, Tsujii, Masato, Ye, Ming, Minami, Isao, Toda, Kanako, Otsuka, Hiromi, Toma, Koji, Arakawa, Takahiro, Araki, Kouji, Iwasaki, Yasuhiko, Shinada, Kayoko, Ogawa, Yoshihiro, Mitsubayashi, Kohji

    Analytical Chemistry   89 ( 22 )   2017

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    DOI: 10.1021/acs.analchem.7b03191

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  • Intelligent Polyphosphoester-Based Biomaterials Reviewed

    Iwasaki, Yasuhiko

    Kobunshi Ronbunshu   74 ( 3 )   2017

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    DOI: 10.1295/koron.2016-0067

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  • Improved Sensitivity of Acetaldehyde Biosensor by Detecting ADH Reverse Reaction-Mediated NADH Fluoro-Quenching for Wine Evaluation Reviewed

    Iitani, Kenta, Chien, Po-Jen, Suzuki, Takuma, Toma, Koji, Arakawa, Takahiro, Iwasaki, Yasuhiko, Mitsubayashi, Kohji

    Acs Sensors   2 ( 7 )   2017

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    DOI: 10.1021/acssensors.7b00184

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  • Hybrid model membrane combining micropatterned lipid bilayer and hydrophilic polymer brush Reviewed

    Morigaki, Kenichi, Nishimura, Toshiki, Tamura, Fuyuko, Tanimoto, Yasushi, Ando, Koji, Sudo, Yuki, Hayashi, Fumio, Iwasaki, Yasuhiko

    Abstracts of Papers of the American Chemical Society   253 ( 23 )   2017

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    DOI: 10.1021/acs.langmuir.7b00463

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  • Bio-sniffer (gas-phase biosensor) with secondary alcohol dehydrogenase (S-ADH) for determination of isopropanol in exhaled air as a potential volatile biomarker Reviewed

    Chien, Po-Jen, Suzuki, Takuma, Tsujii, Masato, Ye, Ming, Toma, Koji, Arakawa, Takahiro, Iwasaki, Yasuhiko, Mitsubayashi, Kohji

    Biosensors &amp; Bioelectronics   91   2017

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    DOI: 10.1016/j.bios.2016.12.050

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  • 双性イオン型ポリマーバイオマテリアルの開発動向

    Iwasaki Y

    Petrotech   39:227-233 ( 3 )   227 - 233   2016.3

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  • Cell Surface Engineering via Methacryloyl-Derivatized Carbohydrates Reviewed

    Yasuhiko Iwasaki

    Biomaterials Nanoarchitectonics   253 - 265   2016.2

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    Control of cell surface nanoarchitectures has attracted attention as a process that can be used in both basic research and for therapeutic applications. This chapter summarizes new strategies for the surface modification of living cells with synthetic polymers and the biointerfacial aspects of such immobilized polymers. In particular, N-methacryloyl mannosamine was synthesized as an artificial precursor of sialic acid, placed in contact with human cells, and incubated. Confirmation of delivery of the methacryloyl groups to carbohydrates on cell surfaces was obtained using a thiol-ene reaction. Various thiol-terminated polymers were covalently immobilized and unnatural functions were introduced to cell surfaces while preserving cell viability.In addition to the thiol-ene reaction, methacryloyl-functionalized carbohydrates were also polymerized via conventional free-radical polymerization. The obtained synthetic hydrogels with embedded glycoproteins were able to bind to selectins expressed on endothelial cells, indicating that the glycoproteins transferred to the hydrogels preserved their function. Selectin-mediated interaction is considered an essential step in the progression of various diseases
    therefore, hydrogels with embedded glycoproteins may be useful in therapeutic and diagnostic applications.Metabolic delivery of methacryloyl groups to the carbohydrates on mammalian cells is a robust technique for cell surface immobilization and provides a means for both controlling cell functions and synthesizing bioactive polymeric materials.

    DOI: 10.1016/B978-0-323-37127-8.00015-7

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  • Optical isopropanol biosensor using NADH-dependent secondary alcohol dehydrogenase (S-ADH) Reviewed

    Chien, Po-Jen, Ye, Ming, Suzuki, Takuma, Toma, Koji, Arakawa, Takahiro, Iwasaki, Yasuhiko, Mitsubayashi, Kohji

    Talanta   159   2016

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    DOI: 10.1016/j.talanta.2016.06.036

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  • Thiolated-2-methacryloyloxyethyl phosphorylcholine protected silver nanoparticles as novel photo-induced cell-killing agents. Reviewed

    Sangsuwan, Arunee, Kawasaki, Hideya, Iwasaki, Yasuhiko

    Colloids and surfaces. B, Biointerfaces   140   2016

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    DOI: 10.1016/j.colsurfb.2015.12.037

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  • Inhibition of matrix metalloproteinases and toxicity of gold and platinum nanoparticles in L929 fibroblast cells Reviewed

    Hashimoto, Masanori, Yamaguchi, Satoshi, Sasaki, Jun-Ichi, Kawai, Koji, Kawakami, Hayato, Iwasaki, Yasuhiko, Imazato, Satoshi

    European Journal of Oral Sciences   124 ( 1 )   2016

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    DOI: 10.1111/eos.12235

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  • Generation of a patterned co-culture system composed of adherent cells and immobilized nonadherent cells Reviewed

    Yamazoe, Hironori, Ichikawa, Takashi, Hagihara, Yoshihisa, Iwasaki, Yasuhiko

    Acta Biomaterialia   31   2016

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    DOI: 10.1016/j.actbio.2015.12.016

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  • Crosslinked duplex DNA nanogels that target specified proteins Reviewed

    Iwasaki, Yasuhiko, Kondo, Jun-ichi, Kuzuya, Akinori, Moriyama, Rui

    Science and Technology of Advanced Materials   17 ( 1 )   2016

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  • Water-soluble complex formation of fullerenes with a biocompatible polymer Reviewed

    Ohata, Tetsuya, Ishihara, Kazuhiko, Iwasaki, Yasuhiko, Sangsuwan, Arunee, Fujii, Shota, Sakurai, Kazuo, Ohara, Yuki, Yusa, Shin-ichi

    Polymer Journal   48 ( 10 )   2016

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    DOI: 10.1038/pj.2016.60

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  • Photo-assisted generation of phospholipid polymer substrates for regiospecific protein conjugation and control of cell adhesion. Reviewed

    Tanaka, Masako, Iwasaki, Yasuhiko

    Acta biomaterialia   40   2016

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    DOI: 10.1016/j.actbio.2016.03.023

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  • Low-Temperature Processable Block Copolymers That Preserve the Function of Blended Proteins. Reviewed

    Iwasaki, Yasuhiko, Takemoto, Kyohei, Tanaka, Shinya, Taniguchi, Ikuo

    Biomacromolecules   17 ( 7 )   2016

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    DOI: 10.1021/acs.biomac.6b00641

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  • Clickable and Antifouling Platform of Poly[(propargyl methacrylate)-ran-(2-methacryloyloxyethyl phosphorylcholine)] for Biosensing Applications Reviewed

    Wiarachai, Oraphan, Vilaivan, Tirayut, Iwasaki, Yasuhiko, Hoven, Voravee P.

    Langmuir   32 ( 4 )   2016

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    DOI: 10.1021/acs.langmuir.5b02727

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  • Antimicrobial Silver Nanoclusters Bearing Biocompatible Phosphorylcholine-Based Zwitterionic Protection Reviewed

    Sangsuwan, Arunee, Kawasaki, Hideya, Matsumura, Yoshinobu, Iwasaki, Yasuhiko

    Bioconjugate Chemistry   27 ( 10 )   2016

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    DOI: 10.1021/acs.bioconjchem.6b00455

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  • Optical and biosensing properties of 2-methacryloyloxyethyl phosphorylcholine-protected Au4 and Au25 nanoclusters

    Yoshimoto J, Sangsuwan A, Osaka I, Yamashita K, Iwasaki Y, Inada M, Arakawa R, Kawasaki H

    J. Phys. Chem. C   119:14319–14325   2015.6

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  • Optical Properties of 2-Methacryloyloxyethyl Phosphorylcholine-Protected Au-4 Nanoclusters and Their Fluorescence Sensing of C-Reactive Protein Reviewed

    Yoshimoto, Junya, Sangsuwan, Arunee, Osaka, Issey, Yamashita, Kazuko, Iwasaki, Yasuhiko, Inada, Mitsuru, Arakawa, Ryuichi, Kawasaki, Hideya

    Journal of Physical Chemistry C   119 ( 25 )   2015

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    DOI: 10.1021/acs.jpcc.5b03934

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  • Poly(dimethylsiloxane) (PDMS) surface patterning by biocompatible photo-crosslinking block copolymers Reviewed

    Kuroda, Keita, Miyoshi, Hiromi, Fujii, Shota, Hirai, Tomoyasu, Takahara, Atsushi, Nakao, Aiko, Iwasaki, Yasuhiko, Morigaki, Kenichi, Ishihara, Kazuhiko, Yusa, Shin-ichi

    Rsc Advances   5 ( 58 )   2015

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    DOI: 10.1039/c5ra08843g

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  • Self-setting particle-stabilized emulsion for hard-tissue engineering Reviewed

    Iwasaki, Yasuhiko, Takahata, Yusuke, Fujii, Syuji

    Colloids and Surfaces B-Biointerfaces   126   2015

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    DOI: 10.1016/j.colsurfb.2014.12.003

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  • Gold Nanoparticles Inhibit Matrix Metalloproteases without Cytotoxicity Reviewed

    Hashimoto, M., Sasaki, J. I., Yamaguchi, S., Kawai, K., Kawakami, H., Iwasaki, Y., Imazato, S.

    Journal of Dental Research   94 ( 8 )   2015

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    DOI: 10.1177/0022034515589282

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  • Anti-Resorptive Functions of Poly(ethylene sodium phosphate) on Human Osteoclasts Reviewed

    Kootala, S., Tokunaga, M., Hilborn, J., Iwasaki, Y.

    Macromol Biosci   15:1634-1640   2015

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    DOI: 10.1002/mabi.201500166

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  • Surface engineering of macrophages with nucleic acid aptamers for the capture of circulating tumor cells Reviewed

    Sugimoto, Shunsuke, Moriyama, Rui, Mori, Takeshi, Iwasaki, Yasuhiko

    Chemical Communications   51 ( 98 )   2015

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    DOI: 10.1039/c5cc06211j

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  • Stabilization of DNA Structures with Poly(ethylene sodium phosphate) Reviewed

    Moriyama, R., Iwasaki, Y., Miyoshi, D.

    J Phys Chem B   119:11969-11977   2015

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    DOI: 10.1021/acs.jpcb.5b03787

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  • Surface engineering for cell-mediated therapy Reviewed

    Iwasaki, Y.

    Kobunshi   64 ( 10 )   2015

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  • α-TCP/PLGA微粒子エマルション骨ペーストの生体適合性評価

    舘山 彰人, 宮治 裕史, 加藤 昭人, 西田 絵利香, 岩崎 泰彦, 藤井 秀司, 滝田 裕子, 吉田 崇, 小川 幸佑, 百瀬 赳人, 村上 秀輔, 長尾 敬志, 川浪 雅光

    日本バイオマテリアル学会大会予稿集   36回   249 - 249   2014.11

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  • Surface modification of mammalian cells through carbohydrate engineering

    Iwasaki Y

    J. Jpn. Soc. Biomater.   32:111-119 ( 2 )   111 - 119   2014.4

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  • Generation of Singlet Oxygen by Photoexcited Au-25(SR)(18) Clusters Reviewed

    Kawasaki, Hideya, Kumar, Santosh, Li, Gao, Zeng, Chenjie, Kauffman, Douglas R., Yoshimoto, Junya, Iwasaki, Yasuhiko, Jin, Rongchao

    Chemistry of Materials   26 ( 9 )   2014

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    DOI: 10.1021/cm500260z

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  • Surface modification of poly(ether ether ketone) with methacryloyl-functionalized phospholipid polymers via self-initiation graft polymerization Reviewed

    Kawasaki, Yoshihiro, Iwasaki, Yasuhiko

    Journal of Biomaterials Science-Polymer Edition   25 ( 9 )   2014

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    DOI: 10.1080/09205063.2014.911570

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  • Spontaneous Assembly into Pseudopolyrotaxane Between Cyclodextrins and Biodegradable Polyphosphoester Ionomers Reviewed

    Tamura, Atsushi, Tokunaga, Masahiro, Iwasaki, Yasuhiko, Yui, Nobuhiko

    Macromolecular Chemistry and Physics   215 ( 7 )   2014

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    DOI: 10.1002/macp.201300774

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  • Improvement of Antifouling Properties of Polyvinylidene Fluoride Hollow Fiber Membranes by Simple Dip Coating of Phosphorylcholine Copolymer via Hydrophobic Interactions Reviewed

    Nishigochi, Shu, Ishigami, Toru, Maruyama, Tatsuo, Hao, Yan, Ohmukai, Yoshikage, Iwasaki, Yasuhiko, Matsuyama, Hideto

    Industrial &amp; Engineering Chemistry Research   53 ( 6 )   2014

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    DOI: 10.1021/ie404094t

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  • Preparation of Biointeractive Glycoprotein-Conjugated Hydrogels through Metabolic Oligosacchalide Engineering Reviewed

    Iwasaki, Yasuhiko, Matsunaga, Aki, Fujii, Shuetsu

    Bioconjugate Chemistry   25 ( 9 )   2014

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1021/bc5003295

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  • Label-free detection of C-reactive protein using highly dispersible gold nanoparticles synthesized by reducible biomimetic block copolymers Reviewed

    Iwasaki, Yasuhiko, Kimura, Toshihiro, Orisaka, Masaki, Kawasaki, Hideya, Goda, Tatsuro, Yusa, Shin-ichi

    Chemical Communications   50 ( 42 )   2014

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    DOI: 10.1039/c4cc01855a

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  • Optimized molecular structure of photoreactive biocompatible block copolymers for surface modification of metal substrate. Reviewed

    Iwasaki Y, Katayama K, Yoshida M, Yamamoto M, Tabata Y

    J. Biomater. Sci., Polym. Edn.   24:882-895   2013.3

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  • Comparative physicochemical properties and cytotoxicity of polyphosphoester ionomers with bisphosphonates Reviewed

    Iwasaki, Yasuhiko, Katayama, Koichi, Yoshida, Munehiro, Yamamoto, Masaya, Tabata, Yasuhiko

    Journal of Biomaterials Science-Polymer Edition   24 ( 7 )   2013

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    DOI: 10.1080/09205063.2012.710823

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  • Thiolated 2-methacryloyloxyethyl phosphorylcholine for an antifouling biosensor platform Reviewed

    Goda, Tatsuro, Tabata, Miyuki, Sanjoh, Mai, Uchimura, Mai, Iwasaki, Yasuhiko, Miyahara, Yuji

    Chemical Communications   49 ( 77 )   2013

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    DOI: 10.1039/c3cc44357d

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  • Surface modification of mammalian cells with stimuli-responsive polymers Reviewed

    Iwasaki, Yasuhiko, Sakiyama, Mizuki, Fujii, Shuetsu, Yusa, Shin-ichi

    Chemical Communications   49 ( 71 )   2013

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    DOI: 10.1039/c3cc44072a

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  • Single nanosized FeO nanocrystals with photoluminescence properties Reviewed

    Sugii, Yuta, Inada, Mitsuru, Yano, Hiroki, Obora, Yasushi, Iwasaki, Yasuhiko, Arakawa, Ryuichi, Kawasaki, Hideya

    Journal of Nanoparticle Research   15 ( 1 )   2013

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    DOI: 10.1007/s11051-012-1379-2

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  • High mineral affinity of polyphosphoester ionomer-phospholipid vesicles Reviewed

    Ikeuchi, Ryota, Iwasaki, Yasuhiko

    Journal of Biomedical Materials Research Part a   101A ( 2 )   2013

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    DOI: 10.1002/jbm.a.34321

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  • Synthesis of amphiphilic polyphosphoester ionomers for surface modification of small unilamellar phospholipid vesicles Reviewed

    Ikeuchi R, Iwasaki Y

    Trans Mater Res Soc Jp   37:365-368   2012.9

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  • 次世代医療を革新するスマートバイオマテリアルの創出

    大矢裕一, 平野義明, 宮田隆志, 田村裕, 青田浩幸, 大洞康嗣, 古池哲也, 岩崎泰彦, 葛谷明紀, 戸田満秋

    技苑   ( 134 )   43 - 49   2012.3

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  • Surface modification of methacryloyl-functionalized living cells Reviewed

    Iwasaki, Yasuhiko, Matsuno, Hiroshi

    Abstracts of Papers of the American Chemical Society   243   2012

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  • SUPPRESSION OF INFLAMMATORY REACTIONS ON MPC POLYMER SURFACES Reviewed

    Iwasaki, Yasuhiko, Ishihara, Kazuhiko, Khang, G

    Handbook of Intelligent Scaffolds For Tissue Engineering and Regenerative Medicine   2012

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  • Cell membrane-inspired phospholipid polymers for developing medical devices with excellent biointerfaces Reviewed

    Iwasaki, Yasuhiko, Ishihara, Kazuhiko

    Science and Technology of Advanced Materials   13 ( 6 )   2012

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    DOI: 10.1088/1468-6996/13/6/064101

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  • Optimized Molecular Structure of Photoreactive Biocompatible Block Copolymers for Surface Modification of Metal Substrates Reviewed

    Iwasaki, Yasuhiko, Matsumoto, Akira, Yusa, Shin-ichi

    Acs Applied Materials &amp; Interfaces   4 ( 6 )   2012

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    DOI: 10.1021/am3006065

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  • Development of a Novel Antifouling Platform for Biosensing Probe Immobilization from Methacryloyloxyethyl Phosphorylcholine-Containing Copolymer Brushes Reviewed

    Akkahat, Piyaporn, Kiatkamjornwong, Suda, Yusa, Shin-ichi, Hoven, Voravee P., Iwasaki, Yasuhiko

    Langmuir   28 ( 13 )   2012

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    DOI: 10.1021/la204229t

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  • pH-responsive flocculation and dispersion behavior of Janus particles in water Reviewed

    Ito, Masanori, Enomoto, Ryusuke, Osawa, Kazuki, Daiko, Yusuke, Yazawa, Tetsuo, Fujii, Syuji, Yokoyama, Yuichi, Miyanari, Yuki, Nakamura, Yoshinobu, Nakao, Aiko, Iwasaki, Yasuhiko, Yusa, Shin-ichi

    Polymer Journal   44 ( 2 )   2012

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    DOI: 10.1038/pj.2011.94

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  • Proposal of a new method for evaluating the frictional properties of tissue engineered cartilage

    Tamura N, Arai M, Iwasaki Y, Ishihara K, Tamada Y, Tomita N

    WIT Transactions on Engineering Sciences   76   89 - 97   2012

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    <p>It is essential to investigate the tribological maturation of tissue engineered cartilage that is to be used in medical applications. The friction properties of tissue engineered cartilage have been measured using flat counter surfaces such as stainless steel, glass or ceramics. However, the measured friction properties were significantly inferior to those of natural cartilage, likely because of cartilage adhesion to the counter surface. In this study, a poly(2-methacryloyloxyethyl phosphorylcholine (MPC)) grafted surface is proposed as an appropriate counter surface for cartilage friction evaluation due to the material's ability to reduce the adhesion and reproduce natural tribological conditions. The poly(MPC) grafted surfaces were prepared by atom transfer radical polymerization (ATRP). The friction coefficients for natural cartilage that were measured on the poly(MPC) grafted surface were lower than 0.01 at the sliding velocities of 0.08 and 0.008 mm/s, which is equivalent to that for natural cartilage-on-cartilage. The friction coefficients for the tissue engineered cartilage were reduced with cultivation time at low sliding velocities. Thus it is suggested that the propose

    DOI: 10.2495/TD120081

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  • Biomedical soft contact-lens sensor for in situ ocular biomonitoring of tear contents Reviewed

    Chu, MingXing, Shirai, Takayuki, Takahashi, Daishi, Arakawa, Takahiro, Kudo, Hiroyuki, Sano, Kenji, Sawada, Shin-ichi, Yano, Kazuyoshi, Iwasaki, Yasuhiko, Akiyoshi, Kazunari, Mochizuki, Manabu, Mitsubayashi, Kohji

    Biomedical Microdevices   13 ( 4 )   2011

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  • Efficient biotinylation of methacryloyl-functionalized nonadherent cells for formation of cell microarrays Reviewed

    Iwasaki, Yasuhiko, Ota, Tatsuya

    Chemical Communications   47 ( 37 )   2011

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    DOI: 10.1039/c1cc12948a

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  • Photoluminescence from Excited Energy Bands in Au(25) Nanoclusters Reviewed

    Sakanaga, Isamu, Inada, Mitsuru, Saitoh, Tadashi, Kawasaki, Hideya, Iwasaki, Yasuhiko, Yamada, Toshiki, Umezu, Ikurou, Sugimura, Akira

    Applied Physics Express   4 ( 9 )   2011

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    DOI: 10.1143/APEX.4.095001

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  • Soft contact lens biosensor for in situ monitoring of tear glucose as non-invasive blood sugar assessment Reviewed

    Chu, MX, Miyajima, K, Takahashi, D, Arakawa, T, Sano, K, Sawada, S, Kudo, H, Iwasaki, Y, Akiyoshi, K, Mochizuki, M, Mitsubayashi, K

    Talanta   83 ( 3 )   2011

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    DOI: 10.1016/j.talanta.2010.10.055

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  • Thermo-responsive behavior of hybrid core cross-linked polymer micelles with biocompatible shells Reviewed

    Goto, F, Ishihara, K, Iwasaki, Y, Katayama, K, Enomoto, R, Yusa, S

    Polymer   52 ( 13 )   2011

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    DOI: 10.1016/j.polymer.2011.04.033

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  • Metabolic Delivery of Methacryloyl Groups on Living Cells and Cell Surface Modification via Thiol-Ene &quot;Click&quot; Reaction Reviewed

    Iwasaki, Yasuhiko, Matsuno, Hiroshi

    Macromolecular Bioscience   11 ( 11 )   2011

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    DOI: 10.1002/mabi.201100242

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  • pH-responsive disruption of 'liquid marbles' prepared from water and poly(6-(acrylamido) hexanoic acid)-grafted silica particles Reviewed

    Inoue, Masamichi, Fujii, Syuji, Nakamura, Yoshinobu, Iwasaki, Yasuhiko, Yusa, Shin-ichi

    Polymer Journal   43 ( 9 )   2011

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    DOI: 10.1038/pj.2011.55

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  • Modern Synthesis and Thermoresponsivity of Polyphosphoesters Reviewed

    Iwasaki, Yasuhiko

    Biomedical Engineering - Frontiers and Challenges   2011

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  • Development of precise tuning method of inter-dot spacing and resonant energy transfer between Au clusters Reviewed

    Inada, Mitsuru, Yoshihara, Yoshihiro, Kawasaki, Hideya, Iwasaki, Yasuhiko, Saitoh, Tadashi, Umezu, Ikurou, Sugimura, Akira, Cabrini, S, Mokari, T

    Nanophotonic Materials Viii   8094   2011

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    DOI: 10.1117/12.893716

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  • Surfactant-free solution synthesis of fluorescent platinum subnanoclusters Reviewed

    Kawasaki, H, Yamamoto, H, Fujimori, H, Arakawa, R, Inada, M, Iwasaki, Y

    Chemical Communications   46 ( 21 )   2010

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    DOI: 10.1039/b925117k

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  • Synthesis of Well-Defined Thermoresponsive Polyphosphoester Macroinitiators Using Organocatalysts Reviewed

    Iwasaki, Y, Yamaguchi, E

    Macromolecules   43 ( 6 )   2010

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    DOI: 10.1021/ma100242s

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  • Synthesis of biocompatible block copolymers using well-defined polyphosphoester macroinitiators Reviewed

    Yamaguchi, Etsuko, Iwasaki, Yasuhiko

    Abstracts of Papers of the American Chemical Society   240   2010

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  • Specific protein binding on phospholipid bilayer array corralled by nonfouling polymer brushes Reviewed

    Iwasaki, Yasuhiko, Nakai, Kosuke, Morigaki, Kenichi

    Abstracts of Papers of the American Chemical Society   240   2010

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  • Molecular recognition on fluidic lipid bilayer microarray corralled by well-defined polymer brushes Reviewed

    Nakai, K, Morigaki, K, Iwasaki, Y

    Soft Matter   6 ( 23 )   2010

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    DOI: 10.1039/c0sm00086h

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  • One-pot Preparation of Water-soluble Blue Luminescent Silica Flakes via Microwave Heating Reviewed

    Iwasaki, Y, Shibata, Y, Watanabe, A, Inada, M, Kawasaki, H, Uchino, T

    Chemistry Letters   39 ( 4 )   2010

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    DOI: 10.1246/cl.2010.370

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  • Stability of the DMF-Protected Au Nanoclusters: Photochemical, Dispersion, and Thermal Properties Reviewed

    Kawasaki, H, Yamamoto, H, Fujimori, H, Arakawa, R, Iwasaki, Y, Inada, M

    Langmuir   26 ( 8 )   2010

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    DOI: 10.1021/la9038842

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  • Improving Blood Compatibility of Natural Rubber by UV-Induced Graft Polymerization of Hydrophilic Monomers Reviewed

    Hoven, VP, Chombanpaew, K, Iwasaki, Y, Tasakorn, P

    Journal of Applied Polymer Science   112 ( 1 )   2009

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    DOI: 10.1002/app.29408

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  • Superlubricious surface mimicking articular cartilage by grafting poly(2-methacryloyloxyethyl phosphorylcholine) on orthopaedic metal bearings Reviewed

    Kyomoto, M, Moro, T, Iwasaki, Y, Miyaji, F, Kawaguchi, H, Takatori, Y, Nakamura, K, Ishihara, K

    Journal of Biomedical Materials Research Part a   91A ( 3 )   2009

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    DOI: 10.1002/jbm.a.32280

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  • Thermoresponsive Polyphosphoesters Bearing Enzyme-cleavable Side Chains Reviewed

    Iwasaki, Y, Kawakita, T, Yusa, S

    Chemistry Letters   38 ( 11 )   2009

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    DOI: 10.1246/cl.2009.1054

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  • A soft and flexible biosensor using a phospholipid polymer for continuous glucose monitoring Reviewed

    Chu, MX, Kudo, H, Shirai, T, Miyajima, K, Saito, H, Morimoto, N, Yano, K, Iwasaki, Y, Akiyoshi, K, Mitsubayashi, K

    Biomedical Microdevices   11 ( 4 )   2009

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  • Synthesis and Properties of Segmented Poly(urethane-urea)s Containing Phosphorylcholine Moiety in the Side-Chain Reviewed

    Nagase, Y, Nakajima, S, Oku, M, Iwasaki, Y, Ishihara, K

    Polymer Journal   40 ( 12 )   2008

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  • Interfacing biomembrane mimetic polymer surfaces with living cells - Surface modification for reliable bioartificial liver Reviewed

    Iwasaki, Y, Takami, U, Sawada, SI, Akiyoshi, K

    Applied Surface Science   255 ( 2 )   2008

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  • Site-specific dense immobilization of antibody fragments on polymer brushes supported by silicone nanofilaments Reviewed

    Iwasaki, Y, Omichi, Y, Iwata, R

    Langmuir   24 ( 16 )   2008

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    DOI: 10.1021/la801327a

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  • Prevention of biofilm formation with a coating of 2-methacryloyloxyethyl phosphorylcholine polymer Reviewed

    Fujii, K, Matsumoto, HN, Koyama, Y, Iwasaki, Y, Ishihara, K, Takakuda, K

    Journal of Veterinary Medical Science   70 ( 2 )   2008

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    DOI: 10.1292/jvms.70.167

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  • Glucose sensor using a phospholipid polymer-based enzyme immobilization method Reviewed

    Kudo, H, Yagi, T, Chu, MX, Saito, H, Morimoto, N, Iwasaki, Y, Akiyoshi, K, Mitsubayashi, K

    Analytical and Bioanalytical Chemistry   391 ( 4 )   2008

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    DOI: 10.1007/s00216-007-1824-8

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  • Covalent immobilization of antibody fragments on well-defined polymer brushes via site-directed method Reviewed

    Iwata, R, Satoh, R, Iwasaki, Y, Akiyoshi, K

    Colloids and Surfaces B-Biointerfaces   62 ( 2 )   2008

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    DOI: 10.1016/j.colsurfb.2007.10.018

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  • Synthesis and biocompatibility of aromatic polyamides by using novel diamine monomers containing phosphorylcholine moiety

    Proceedings of the School of Engineering of Tokai University   48 ( 1 )   11 - 17   2008

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  • ホスホリルコリン基含有芳香族ジアミンモノマーを用いたセグメント化ポリウレタン-ウレアの合成と性質

    那川大輔, 堀口健二, 長瀬裕, 岩崎泰彦, 石原一彦

    日本バイオマテリアルシンポジウム2008講演予稿集   P1-24   2008

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  • Experimental and Theoretical Study on Swirl Braked Labyrinth Seal

    T. Iwatsubo, Y. Iwasaki

    Journal of System Design and Dynamics   Vol. 2, No.1, pp. 451-462   2008

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  • Synthesis of a novel diamine monomer and aromatic polyamides containing phosphorylcholine group Reviewed

    Horiguchi K, Shimoyamada N, Nagawa D, Nagase Y, Iwasaki Y, Ishihara K

    Trans Mater Res Soc Jpn   33:1261-1264   2008

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  • Cell-specific delivery of polymeric nanoparticles to carbohydrate-tagging cells Reviewed

    Iwasaki, Y, Maie, H, Akiyoshi, K

    Biomacromolecules   8   2007

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    DOI: 10.1021/bm700606Z

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  • Site-directed immobilization of antibodies on well-defined polymer brushes Reviewed

    Iwata, R., Iwasaki, Y., Akiyoshi, K.

    European Cells and Materials   14 ( SUPPL.3 )   66 - 66   2007

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  • Enzyme-degradable phosphorylcholine porous hydrogels cross-linked with polyphosphoesters for cell matrices Reviewed

    Wachiralarpphaithoon, C, Iwasaki, Y, Akiyoshi, K

    Biomaterials   28 ( 6 )   2007

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    DOI: 10.1016/j.biomaterials.2006.10.024

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  • ホスホリルコリン基含有芳香族ポリアミドの合成と生体適合性

    下山田直矢, 奥 正敬, 長瀬 裕, 岩崎泰彦, 石原一彦

    東海大学紀要工学部   46 ( 2 )   5 - 10   2007

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  • Patterning of endothelial cells for designed capillary formation Reviewed

    Henmi, C, Nakamura, M, Nishiyama, Y, Watanabe, A, Iwasaki, Y, Morita, I, Yamaguchi, K, Mochizuki, S, Takiura, K, Nakagawa, H

    Tissue Engineering   13 ( 7 )   2007

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  • Immobilization of polyethylene glycol terminated with amine to titanium surface by electrodeposition Reviewed

    Tanaka, Y., Doi, H., Iwasaki, Y., Yoneyama, T., Hanawa, T.

    Advanced Materials Research   15-17   2007

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    Publishing type:Research paper (scientific journal)   Publisher:Advanced Materials Research  

    DOI: 10.4028/www.scientific.net/AMR.15-17.205

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  • Salt effect on the heat-induced association Behavior of gold nanoparticles coated with Poly(N-isopropylacrylamide) prepared via reversible addition - Fragmentation chain transfer (RAFT) radical polymerization Reviewed

    Yusa, SI, Fukuda, K, Yamamoto, T, Iwasaki, Y, Watanabe, A, Akiyoshi, K, Morishima, Y

    Langmuir   23 ( 26 )   2007

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    DOI: 10.1021/la702741q

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  • Novel thermoresponsive polymers having biodegradable phosphoester backbones Reviewed

    Iwasaki, Y, Wachiralarpphaithoon, C, Akiyoshi, K

    Macromolecules   40   2007

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    DOI: 10.1021/ma0715573

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  • Electrodeposition of amine-terminated poly(ethylene glycol) to titanium surface Reviewed

    Tanaka, Y, Doi, H, Iwasaki, Y, Hiromoto, S, Yoneyama, T, Asami, K, Imai, H, Hanawa, T

    Materials Science &amp; Engineering C-Biomimetic and Supramolecular Systems   27 ( 2 )   2007

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    DOI: 10.1016/j.msec.2006.03.007

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  • Control of cell function on carbohydrate-immobilized phosphorylcholine polymer surfaces Reviewed

    Iwasaki, Y., Takami, U., Shinohara, Y., Akiyoshi, K.

    European Cells and Materials   14 ( SUPPL.3 )   72 - 72   2007

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  • Selective biorecognition and preservation of cell function on carbohydrate-immobilized phosphorylcholine polymers Reviewed

    Iwasaki, Y, Takami, U, Shinohara, Y, Kurita, K, Akiyoshi, K

    Biomacromolecules   8 ( 9 )   2007

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    DOI: 10.1021/bm700478d

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  • Polymer brushes in nanopores surrounded by silicon-supported tris(trimethylsiloxy)silyl monolayers Reviewed

    Hoven, VP, Srinanthakul, M, Iwasaki, Y, Iwata, R, Kiatkamjornwong, S

    Journal of Colloid and Interface Science   314 ( 2 )   2007

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    DOI: 10.1016/j.jcis.2007.05.088

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  • Preparations of aromatic diamine monomers and copolyamides containing phosphory1choline moiety and the biocompatibility of copolyamides Reviewed

    Nagase, Y, Oku, M, Iwasaki, Y, Ishihara, K

    Polymer Journal   39 ( 7 )   2007

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    DOI: 10.1295/polymj.PJ2006253

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  • Surface modification with well-defined biocompatible triblock copolymers - Improvement of biointerfacial phenomena on a poly(dimethylsiloxane) surface Reviewed

    Iwasaki, Y, Takamiya, M, Iwata, R, Yusa, S, Akiyoshi, K

    Colloids and Surfaces B-Biointerfaces   57 ( 2 )   2007

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    DOI: 10.1016/j.colsurfb.2007.02.007

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  • Feasibility of a tiny centrifugal blood pump (TinyPump) for pediatric extracorporeal circulatory support Reviewed

    Ohuchi, K, Hoshi, H, Iwasaki, Y, Ishihara, K, Yoshikawa, M, Ugaki, S, Ishino, K, Osaki, S, Kotani, Y, Sano, S, Takatani, S

    Artificial Organs   31 ( 5 )   2007

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    DOI: 10.1111/j.1525-1594.2007.00401.x

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  • High lubricious surface of cobalt-chromium-molybdenum alloy prepared by grafting poly(2-methacryloyloxyethyl phosphorylcholine) Reviewed

    Kyomoto, M, Iwasaki, Y, Moro, T, Konno, T, Miyaji, F, Kawaguchi, H, Takatori, Y, Nakamura, K, Ishihara, K

    Biomaterials   28 ( 20 )   2007

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    DOI: 10.1016/j.biomaterials.2007.03.010

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  • DDS by the nanoparticle recognizing unnatural sugars of cell-surface

    Haruki Maie, Yasuhiko Iwasaki, Kazunari Akiyoshi

    Polymer Preprints, Japan   55 ( 2 )   5345 - 5346   2006

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    Polymeric nanoparticles were prepared by a hydrazide-functionalized MPC polymer (PMBH) as an emulsifier. The human cervical adenocarcinoma (HeLa) cells having noncanonical carbohydrates were prepared by N-levulinoylmannosamine (ManLev) treatment and used as the target cells. The PMBH nanoparticles can adsorb doxorubicin on their surfaces through hydrophobic interaction. When the PMBH/DOX nanoparticles were in contact with ManLev-treated HeLa cells, the number of living cells was dramatically decreased. However, there was little cytotoxicity to native cells without noncanonical carbohydrates on their surface.

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  • Synthesis and characterization of peptide-conjugated polyphosphoesters

    Shinji Enomoto, Yasuhiko Iwasaki, Kazunari Akiyoshi

    Polymer Preprints, Japan   55 ( 2 )   4848   2006

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    There has been a great deal of interest in polyphosphates, which are biodegradable through hydrolysis and possibly through enzymatic digestion of phosphate linkages under physiological conditions. We have synthesized polyphosphoesters conjugated with oligopeptides as novel bioactive polymer materials. 2-Ethyl-2-oxo-1,3,2-dioxaphospholane(EP) and 2-propargyl-2-oxo-1,3,2- dioxaphospholane(PGP) were copolymerized by ring-opening polymerization. Peptides were immobilized with polyphosphoesters through the click chemistry. The composition of peptides in a polymer was varied with changing in the fraction of PGP.

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  • Antibody immobilized well-defined block copolymer brushes for biorecognition surface

    Ryoko Iwata, Yasuhiko Iwasaki, Kazunari Akiyoshi

    Polymer Preprints, Japan   55 ( 2 )   4846   2006

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    Well-defined block copolymer brushes consisting of MPC and GMA were prepared on silicon substrates by atom transfer radical polymerization. The polymer thickness was controlled by the polymerization time. The pyridyl disulfide moieties were introduced into the block copolymer brushes via reaction with epoxy group in GMA units. The amount of pyridyl disulfide moieties could be controlled by changing the density and the thickness of polymer brushes. Furthermore, Fab'-fragment which has thiol groups in opposite side of antigen binding domain reacted with block copolymer brushes with pyridyl disulfide moieties. The activity of Fab' fragment will be discussed.

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  • Synthesis and functionality of poly(urethane-urea) containing phosphorylcholine moiety

    Yu Nagase, Satoru Nakajima, Naoya Shimoyamada, Yasuhiko Iwasaki, Kazuhiko Ishihara

    Polymer Preprints, Japan   55 ( 2 )   3355 - 3356   2006

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    In order to improve the biocompatibility of segmented polyurethane (SPU) which has been widely used as a biomedical material, the synthesis of segmented poly(urethane-urea) containing phosphorylcholine (PC) moiety (SPUU) was carried out by using aromatic diamine compound with PC unit as a monomer. The obtained poly(urethane-urea) was soluble in aprotic polar solvents such as NMP, DMSO and DMF, but insoluble in water, alcohol and other organic solvents. It was confirmed from the results of blood contacting experiments that the polymer exhibited the excellent biocompatibility, even though the PC content was around 10 mol%, as compared with polyurethane without PC unit. From the results of stress-strain measurements, SPUU membranes exhibited the elastomeric mechanical properties similar to those of SPU.

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  • Design of biodegradable amphiphilic polyphosphates with well-defined hydrophilic graft chains Reviewed

    Iwasaki, Y, Akiyoshi, K

    Abstracts of Papers of the American Chemical Society   231   2006

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  • Stress response of adherent cells on a polymer blend surface composed of a segmented polyurethane and MPC copolymers Reviewed

    Sawada, SI, Iwasaki, Y, Nakabayashi, N, Ishihara, K

    Journal of Biomedical Materials Research Part a   79A ( 3 )   2006

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    DOI: 10.1002/jbm.a.30820

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  • A flexible and wearable glucose sensor based on functional polymers with Soft-MEMS techniques Reviewed

    Kudo, H, Sawada, T, Kazawa, E, Yoshida, H, Iwasaki, Y, Mitsubayashi, K

    Biosensors &amp; Bioelectronics   22 ( 4 )   2006

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    DOI: 10.1016/j.bios.2006.05.006

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  • Synthesis of aromatic carboxylic acid compound containing phosphorylcholine moiety and the polymer reaction with ethyl cellulose Reviewed

    Tadokoro, Y, Nagase, Y, Iwasaki, Y, Ishihara, K, Somiya, S, Doyama, M

    Trans Mater Res Soc Jpn   31 ( 4 )   2006

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  • High functional hollow fiber membrane modified with phospholipid polymers for a liver assist bioreactor Reviewed

    Ye, SH, Watanabe, J, Takai, M, Iwasaki, Y, Ishihara, K

    Biomaterials   27 ( 9 )   2006

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    DOI: 10.1016/j.biomaterials.2005.09.041

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  • Poly(MPC-co-BMA) coating reduces the adhesion of Candida albicans to poly(methyl methacrylate) surfaces Reviewed

    Hatsuno K, Mukohyama H, Horiuchi S, Iwasaki Y, Yamamoto N, Akiyoshi K, Taniguchi H

    Prosthodont Res Pract   5:21-25 ( 1 )   21 - 25   2006

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    <b>Purpose:</b> The aim of the present study was to develop a new and simple method using PMB to prevent plaque colonization on denture surfaces.<br><b>Methods:</b> PMB polymerized with MPC polymer and BMA was prepared as a coating material. Water-insoluble PMB composed of 30 mol% MPC units (PMB30), water-soluble PMB composed of 80 mol% MPC units (PMB80) and clear PMMA disks were prepared. The PMMA disks were dip-coated in 0.5 wt% PMB30 solution or 0.5 wt% PMB80 solution. To examine the PMB coatings' durability, the PMB-coated disks were immersed in distilled water. The PMB elution ratio was measured using a phosphorus analysis. To evaluate the effect of the PMB coating on <i>Candida albicans</i> (<i>C. albicance</i>) adhesion, PMB-coated and uncoated disks were cultured in a solution containing <i>C. albicans</i> for 48 hours. Half of the disks in each group were not washed, and the remaining disks were washed with distilled water to examine the effect of washing. All the PMMA disks were observed and photographed, and the resulting images were analyzed using imaging analysis software.<br><b>Results:</b> In the first 48 hours, approximate 14 % of the PMB30-coating and 12 % of the PMB80-coating were eluted into the distilled water. The adhesion of <i>C. albicans</i> to the PMB30-coated or the PMB80-coated PMMA disks was significantly reduced in both the washed and unwashed groups, compared with the uncoated control disks.<br><b>Conclusion:</b> PMB coating prevents the adhesion of <i>C. albicans</i> to PMMA.

    DOI: 10.2186/prp.5.21

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  • Synthesis and characterization of amphiphilic polyphosphates with hydrophilic graft chains and cholesteryl groups as nanocarriers Reviewed

    Iwasaki, Y, Akiyoshi, K

    Biomacromolecules   7 ( 5 )   2006

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    DOI: 10.1021/bm050917w

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  • Platelet separation from whole blood in an aqueous two-phase system with water-soluble polymers Reviewed

    Sumida, E, Iwasaki, Y, Akiyoshi, K, Kasugai, S

    Journal of Pharmacological Sciences   101 ( 1 )   2006

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    DOI: 10.1254/jphs.FP0060062

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  • Dual mode bioreactions on polymer nanoparticles covered with phosphorylcholine group Reviewed

    Ito, T, Watanabe, J, Takai, M, Konno, T, Iwasaki, Y, Ishihara, K

    Colloids and Surfaces B-Biointerfaces   50 ( 1 )   2006

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    DOI: 10.1016/j.colsurfb.2006.04.006

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  • Highly wettable polyethylene films generated by spontaneous surface enrichment of perfluoroalkylated phosphorylcholines Reviewed

    Iwasaki, Y, Akiyoshi, K

    Journal of Applied Polymer Science   102 ( 3 )   2006

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    DOI: 10.1002/app.24676

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  • Flexible glucose sensor using biocompatible polymers Reviewed

    Kudo, H, Sawada, T, Chu, MX, Saito, T, Saito, H, Otsuka, K, Iwasaki, Y, Mitsubayashi, K

    2006 Ieee Sensors, Vols 1-3   2006

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  • Covalent immobilization of antibody on well-defined block polymer brushes

    Ryoko Iwata, Yasuhiko Iwasaki, Kazunari Akiyoshi

    Polymer Preprints, Japan   55 ( 1 )   1984   2006

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    Well-defined block polymer brushes consisting of MPC and GMA (PMPC-b-PGMA brushes) were prepared on silicon substrates via ATRP. The pyridyl disulfide moieties were introduced into the block polymer brushes through the reaction with epoxy group in GMA units. The amount of pyridyl disulfide moieties could be controlled by changing the density and the thickness of polymer brushes. Fab'-fragment which has thiol groups in opposite side of antigen binding domain was reacted with block polymer brushes with pyridyl disulfide moieties and analyzed by X-ray photoelectron spectroscopy (XPS). In PMPC-b-PGMA brushes, N1s, signal at the binding energy of about 400 eV and 403 eV was observed. These signals could be attributed to the amine group in Fab'-fragment and the choline group in MPC unit, respectively. While in PMPC brushes, there was only a signal at the binding energy of about 403 eV. Furthermore, S 2p signal was observed in PMPC-i-PGMA brushes and not in PMPC brushes. From these results, it was confirmed that Fab'-fragment could be covalently immobilized via thiol-disulfide exchange. The activity of antibody against antigen will be reported.

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  • Preparation of biomembrane-inspired polymers having sugar moieties

    Yasuhiko Iwasaki, Yurika Shinohara, Kimio Kurita, Kazunari Akiyoshi

    Polymer Preprints, Japan   55 ( 1 )   1985   2006

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    In natural environment, carbohydrates on the cell surface contribute to most communications between the cell and its environments. 2- Methacryloyloxyethyl phosphorylcholine (MPC) polymers exhibit a surface property that resists nonspecific protein adsorption and cell adhesion, i.e., "biofouling". It was then hypothesized that carbohydrate- immobilization on a MPC polymer surface might be promising way to control protein/material or cell/material interactions. The copolymerization of MPC, n-butyl methacrylate (BMA), and 2-lactobionamidoethyl methacrylate (LAMA) was carried out by radical polymerization. Human hepatocellular liver carcinoma cell line (HepG2) cells were seeded onto polymer films ,and cultured in for 24 and 96 hours. Proliferative ratio (24h-96h culture) was increased with an increase in a LAMA composition of copolymers . Moreover, the ratio on copolymers having 3.0 mol % LAMA unit became about twice compared with that on PBMA. This result indicates that chemistry structure of a substrate influenced adhesion and proliferation of HepG2.

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  • Biorecognition surface prepared with biomembrane-inspired polymers

    Yasuhiko Iwasaki, Yurika Shinohara, Utae Takami, Kimio Kurita, Kazunari Akiyoshi

    Polymer Preprints, Japan   55 ( 2 )   5002 - 5003   2006

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    In living system, carbohydrates on the cell surface contribute to most communications between the cell and its environments. 2-Methacryloyloxyethyl phosphorylcholine (MPC) polymers exhibit a surface property that resists nonspecific protein adsorption and cell adhesion, i.e., "biofouling". It was then hypothesized that carbohydrate-immobilization on a MPC polymer surface might be promising way to control protein/material or cell/material interactions. The copolymerization of MPC, n-butyl methacrylate (BMA), and 2-lactobionamidoethyl methacrylate (LAMA) was carried out by radical polymerization. Human hepatocellular liver carcinoma cell line (HepG2) cells and mouse fibroblast (NIH-3T3) cells were seeded onto polymer films, and cultured in for 24, 96, and 168 hours. On PMBL surface, the density of adherent HepG2 cells having asialoglycoprotein receptors was significantly higher than that on poly(MPC-co-BMA) due to ligand/receptor interaction.

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  • Synthesis and biocompatibility of polyamides containing phosphorylcholine moiety

    Naoya Shimoyamada, Azusa Yogo, Kenji Horiguchi, Yu Nagase, Eiichi Akiyama, Yasuhiko Iwasaki, Kazuhiko Ishihara

    Polymer Preprints, Japan   55 ( 2 )   4847   2006

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    Recently, 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer has been reported as an ideal biocompatible material. In this study, in order to develop the durability of PC-containing polymer, the synthesis of novel aromatic diamine compounds containing phosphorylcholine (PC) group with different spacer structures was carried out to prepare aromatic polyamides with PC moiety. The obtained polyamide had a large molecular weight, and the tough membrane was obtained by solvent casting method. In case of the homopolymer membrane surface, the XPS signal was observed in the P2p region which was derived from the PC group. Therefore, these polyamides exhibited biocompatibility, which would be due to the surface derived from the PC side chain.

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  • Synthesis and biocompatibility of poly (urethane-urea) containing phosphorylcholine moiety

    Nakajima Satoru, Shimoyamada Naoya, Katumata Kenichi, Nagase Yu, Iwasaki Yasuhiko, Ishihara Kazuhiko

    4951 - 4952   2005.12

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    <p>In order to improve the biocompatibility of segmented polyurethane (SPU) which has been widely used as a biomedical material, the synthesis of segmented poly(urethane-urea) containing phosphorylcholine (PC) (SPUU) moiety was carried out by using aromatic diamine compound with PC unit as a monomer. The obtained poly(urethane-urea) was soluble in aprotic polar solvents such as NMP, DMSO and DMF, but insoluble in water, alcohol and acetone. In addition, it was confirmed from the results of blood contacting experiments that the polymer exhibited the excellent biocompatibility, even though the PC content was around 10 mol%, as compared with polyurethane without PC unit. From the results of stress-strain measurements, SPUU membranes exhibited the excellent mechanical properties, where the mechanical properties of SPUU were almost as same as those of SPU.</p>

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  • Synthesis and property of aromatic polyamides containing phosphorylcholine moiety

    Shimoyamada Naoya, Oku Masataka, Nakajima Satoru, Nagase Yu, Iwasaki Yasuhiko, Ishihara Kazuhiko

    2005.12

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    <p>Recently, 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer has been reported as an ideal biocompatible material. In this study, in order to develop the durability of MPC polymer, the synthesis of a novel aromatic diamine compound containing phosphorylcholine (PC) group was carried out to prepare aromatic polyamides with PC moiety. The obtained polyamides exhibited biocompatibility, however, XPS signals in the P<sub>2P</sub> region were hardly observed on the film surface. Therefore, it was found that PC units were scarcely concentrated on the surface of polymer membrane in such aromatic polyamides because of the rigid main chain structure.</p>

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  • Evaluation of 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer-coated dressing on surgical wounds

    Katakura Osamu, Morimoto Nobuyuki, Iwasaki Yasuhiko, Akiyoshi Kazunari, Kasugai Shohei

    Journal of medical and dental sciences   52 ( 2 )   115 - 121   2005.6

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    The ideal dressing material is bio-inert andkeeps the wound site moist. It is equally importantthat no regenerative tissue is peeled off on theremoval of the dressing. 2-Methacryloyloxyethylphosphorylcholine (MPC) has a phospholipidpolar group that mimics a biomembrane. We preparedpoly [MPC-co-n-dodecyl methacrylate(DMA)] (PMD), using conventional radical polymerizationwith 2,2'-azobisisobutyronitrile as an initiator,and coated it on polyurethane (PU;Tecoflex<sup>&reg;</sup> 60 Thermedics Inc.) membrane. Fullthicknesssurgical wounds were made on the dorsalskin of rats and wound healing was comparedunder the following three conditions: air-exposedcontrol (no dressing), PU dressing, and PMDdressing. At 3, 4 and 7 days after the operation, thewound sizes of the PMD dressings were smallerthan the non-dressed wound, and at 6 and 7 daysafter the operation, the wound sizes of PU dressingwere smaller than that of the air-exposed group.But there were no significant difference betweenthe PMD dressing group and PU dressing group.Histologically, scab formation was not observed onthe PU or PMD-dressed wounds. However, in theair-exposed control, a scab was formed and reepithelializationof the wound site was prevented.Additionally, no damage was observed in the histologicalsection of PMD dressed wound after thewound was cured. These results indicate thatPMD dressing (PMD-coated PU membrane) hasthe potential to provide an inert environment forwound healing as well as PU.

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    Other Link: http://search.jamas.or.jp/link/ui/2006247811

  • Preparation and biocompatibitity of aromatic polyamides containing phosphorylcholine moiety Reviewed

    Oku, M, Nakajima, S, Tadokoro, Y, Shimoyamada, N, Nagase, Y, Iwasaki, Y, Ishihara, K, Somiya, S, Doyama, M

    Trans Mater Res Soc Jpn   30 ( 4 )   2005

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  • Selective cell attachment to a biomimetic polymer surface through the recognition of cell-surface tags Reviewed

    Iwasaki, Y, Tabata, E, Kurita, K, Akiyoshi, K

    Bioconjugate Chemistry   16 ( 3 )   2005

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    DOI: 10.1021/bc049707r

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  • Phospholipid polymer surfaces reduce bacteria and leukocyte adhesion under dynamic flow conditions Reviewed

    Patel, JD, Iwasaki, Y, Ishihara, K, Anderson, JM

    Journal of Biomedical Materials Research Part a   73A ( 3 )   2005

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    DOI: 10.1002/jbm.a.30302

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  • Design of functional hollow fiber membranes modified with phospholipid polymers for application in total hemopurification system Reviewed

    Ye, SH, Watanabe, J, Takai, M, Iwasaki, Y, Ishihara, K

    Biomaterials   26 ( 24 )   2005

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    DOI: 10.1016/j.biomaterials.2005.01.049

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  • Cell separation in microcanal coated with electrically charged phospholipid polymers Reviewed

    Ito, T, Iwasaki, Y, Narita, T, Akiyoshi, K, Ishihara, K

    Colloids and Surfaces B-Biointerfaces   41 ( 2-3 )   2005

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    DOI: 10.1016/j.colsurfb.2004.12.002

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  • In situ modification on cellulose acetate hollow fiber membrane modified with phospholipid polymer for biomedical application Reviewed

    Ye, SH, Watanabe, J, Iwasaki, Y, Ishihara, K

    Journal of Membrane Science   249 ( 1-2 )   2005

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    DOI: 10.1016/j.memsci.2004.10.006

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  • Well-controlled nanobiointerface generated from phosphorylcholine block copolymers brushes via a ”grafting from” process” Reviewed

    Iwata R, Iwasaki Y, Akiyoshi K, Takahara A

    Trans Mater Res Soc Jpn   30:735-738   2005

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  • Biocompatible inkjet printing technique for designed seeding of individual living cells Reviewed

    Nakamura, M, Kobayashi, A, Takagi, F, Watanabe, A, Hiruma, Y, Ohuchi, K, Iwasaki, Y, Horie, M, Morita, I, Takatani, S

    Tissue Engineering   11 ( 11-12 )   2005

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    DOI: 10.1089/ten.2005.11.1658

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  • Evaluation of 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer-coated dressing on surgical wounds Reviewed

    Osamu Katakura, Nobuyuki Morimoto, Yasuhiko Iwasaki, Kazunari Akiyoshi, Shohei Kasugai

    Journal of Medical and Dental Sciences   52 ( 2 )   115 - 121   2005

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    The ideal dressing material is bio-inert and keeps the wound site moist. It is equally important that no regenerative tissue is peeled off on the removal of the dressing. 2-Methacryloyloxyethyl phosphorylcholine (MPC) has a phospholipid polar group that mimics a biomembrane. We prepared poly [MPC-co-n-dodecyl methacrylate (DMA)] (PMD), using conventional radical polymerization with 2,2'-azobisisobutyronitrile as an initiator, and coated it on polyurethane (PU
    Tecoflex ® 60 Thermedics Inc.) membrane. Full-thickness surgical wounds were made on the dorsal skin of rats and wound healing was compared under the following three conditions: air-exposed control (no dressing), PU dressing, and PMD dressing. At 3, 4 and 7 days after the operation, the wound sizes of the PMD dressings were smaller than the non-dressed wound, and at 6 and 7 days after the operation, the wound sizes of PU dressing were smaller than that of the air-exposed group. But there were no significant difference between the PMD dressing group and PU dressing group. Histologically, scab formation was not observed on the PU or PMD-dressed wounds. However, in the air-exposed control, a scab was formed and re-epithelialization of the wound site was prevented. Additionally, no damage was observed in the histological section of PMD dressed wound after the wound was cured. These results indicate that PMD dressing (PMD-coated PU membrane) has the potential to provide an inert environment for wound healing as well as PU.

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  • Hybrid nanogels with physical and chemical cross-linking structures as nanocarriers Reviewed

    Morimoto, N, Endo, T, Ohtomi, M, Iwasaki, Y, Akiyoshi, K

    Macromolecular Bioscience   5 ( 8 )   2005

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    DOI: 10.1002/mabi.200500051

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  • Design of hybrid hydrogels with self-assembled nanogels as cross-linkers: Interaction with proteins and chaperone-like activity Reviewed

    Morimoto, N, Endo, T, Iwasaki, Y, Akiyoshi, K

    Biomacromolecules   6 ( 4 )   2005

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    DOI: 10.1021/bm050156x

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  • Interaction between biomaterials and cell tissues Reviewed

    Y. Iwasaki, N. Nakabayashi

    Surfaces and Interfaces for Biomaterials   389 - 413   2005

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    DOI: 10.1533/9781845690809.3.389

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  • ホスホリルコリン基含有ポリ(ウレタン-ウレア)の合成と生体適合性

    中島 智, 奥 正敬, 長瀬 裕, 岩崎 泰彦, 石原 一彦

    東海大学紀要工学部   44 ( 2 )   1 - 8   2005

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  • Phosphorylcholine-containing polymers for biomedical applications Reviewed

    Iwasaki, Y, Ishihara, K

    Analytical and Bioanalytical Chemistry   381 ( 3 )   2005

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    DOI: 10.1007/s00216-004-2805-9

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  • Segmented polyurethane modified by photopolymerization and cross-linking with 2-methacryloyloxyethyl phosphorylcholine polymer for blood-contacting surfaces of ventricular assist devices Reviewed

    Kobayashi, K., Ohuchi, K., Hoshi, H., Morimoto, N., Iwasaki, Y., Takatani, S.

    J Artif Organs   8 ( 4 )   2005

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    DOI: 10.1007/s10047-005-0308-x

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  • Preparation of MPC polymer-coated nanoparticles reacting to unnatural carbohydrates of a cell surface

    Haruki Maie, Yasuhiko Iwasaki, Kazunari Akiyoshi, Michiko Ohtomi

    Polymer Preprints, Japan   54 ( 1 )   2183   2005

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    Polymeric nanoparticles (∼200 nm in diameter) coated with 2-methacryloyloxyethyl phosphorylcholine (MPC) copolymers having hydrazide groups were prepared to develop novel drug carriers, which can react with carbohydrates of a specific cell. The Z-potential of the nanoparticles was approximately zero. When the nanoparticles were incubated with the human cervical adenocarcinoma (HeLa) cells expressing N-levulinoyl sialic acid (SiaLev) moiety on membrane proteins, the nanoparticles attached on the cell surface. However, the nanoparticles did not interact with native HeLa cells (non-SiaLev).

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  • Synthesis and property of poly(urethane-urea) containing phosphorylcholine moiety

    Satoru Nakajima, Masataka Oku, Yu Nagase, Yasuhiko Iwasaki, Kazuhiko Ishihara

    Polymer Preprints, Japan   54 ( 1 )   2259   2005

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    In order to improve the biocompatibility of segmented polyurethane which has been widely used as a biomedical material, the synthesis of poly(urethane-urea) containing phosphorylcholine (PC) moiety was carried out by using aromatic diamine compound with PC unit as a monomer. The obtained poly(urethane-urea) was soluble in aprotic polar solvents such as NMP, DMSO and DMF, but insoluble in water, alcohol and acetone. In addition, it was confirmed from the results of blood contacting experiments that the polymer exhibited the excellent biocompatibility, even though the PC content was around 10 mol%, as compared with polyurethane without PC unit.

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  • Well-defined block polymer brushes for biorecognition surface

    Ryoko Iwata, Yasuhiko Iwasaki, Kazunari Akiyoshi

    Polymer Preprints, Japan   54 ( 2 )   5149 - 5150   2005

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    Well-defined block polymer brushes consisting of MPC and GMA were fabricated on silicon substrates by ATRP. 3-(2-bromoisobutyryl) propyldimethylchlorosilane (BDCS)-modified silicon substrates were applied for ATRP of MPC using Cu(I)Br and 2,2'-Dipyridyl (bpy) for 3h. Then, GMA was polymerized from poly(MPC)(PMPC) brush using Cu(I)Br and bpy at ambient temperature. Semilogarithmic plot of monomer concentration was linear with polymerization time. This suggests that the concentration of radicals was constant during the polymerization. The PGMA brush thickness increased linearly with polymerization time. The C/O ratio of the PMPC-b-PGMA block polymer brush surfaces determined by X-ray photoelectron spectroscopy (XPS) became similar to that of the GMA molecule (C/O=2.3) at longer polymerization time. And the water contact angle of PMPC brush increased after block polymerization of GMA. These results indicated that GMA was polymerized from the terminal of PMPC brushes. The pyridyl disulfide group for immobilization of thiol containing biomolecules was also introduced via reaction with epoxy group.

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  • Synthesis of aromatic carboxylic acid compound containing phosphorylcholine moiety and the application to polymer reaction

    Yoshinori Tadokoro, Masataka Oku, Yu Nagase, Yasuhiko Iwasaki, Kazuhiko Ishihara

    Polymer Preprints, Japan   54 ( 2 )   5011   2005

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    Polymeric materials containing a phosphorylcholine (PC) group has been known to show the improved biocompatibility, which can be used for biomedical field. In this work, a novel aromatic carboxylic acid compound containing PC group (CPC) was synthesized, in order to introduce the PC group into the polymers containing hydroxyl or amino group by polymer reactions. The reaction between CPC and ethyl cellulose was carried out using DCC as a condensation reagent to obtain ethyl cellulose partially substituted with PC group. The chemical structure of the obtained cellulose was confirmed by 1H-NMR and FT-IR, and the elements of PC group were observed on the film surface by XPS analysis.

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  • Synthesis and characterization of porous phosphorylcholine polymer hydrogel cross-linked with methacryloyl-functionalized polyphosphates

    Chookaet Wachiralarpphaithoon, Yasuhiko Iwasaki, Kazunari Akiyoshi

    Polymer Preprints, Japan   54 ( 1 )   2220   2005

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    Porous phosphorylcholine hydrogels cross-linked methacryloyl-functionalized polyphosphates were prepared by copolymerization with 2-methacryloyloxyethyl phosphorylcholine (MPC). To control porous structures of hydrogels, salt-leaching and gas-foaming techniques were applied. The structures of freeze-dried hydrogels were observed by SEM and the pore sizes in hydrogels were well controlled by the above techniques. The degradation of hydrogels depended on the rate of hydrolysis of polyphosphates. The mechanical properties of hydrogels were determined torsional mechanical analysis. The elastic modulus of hydrogels was increased with an increase in the cross-link density. Incorporation of cells in porous hydrogels and the effect of a hydrogel on cell viability will be discussed.

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  • Well-defined block polymer brushes for protein immobilization

    Ryoko Iwata, Yasuhiko Iwasaki, Kazunari Akiyoshi

    Polymer Preprints, Japan   54 ( 1 )   1609   2005

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    Well-defined block polymer brushes consisting of MPC and GMA were fabricated on silicon substrates by ATRP. 3-(2-bromoisobutyryl) propyldimethylchlorosilane (BDCS) was immobilized on silicon substrates. BDCS-modified silicon substrates were applied for ATRP of MPC using Cu(I)Br, 2,2'-Dipyridyl (bpy) via aqueous and alcoholic media (water / methanol = 1 / 4) at ambient temperature. Then, GMA was polymerized from poly(MPC)(PMPC) brush using Cu(I)Br, bpy via a mixed solvent of 7 parts methyl-ethyl-ketone (MEK) and 3 parts ethanol at ambient temperature. The PGMA brush thickness increased linearly with polymerization time. The C/O ratio of the PMPC-b-PGMA block polymer brush surfaces determined by X-ray photoelectron spectroscopy (XPS) was similar to that of the GMA molecule (C/O=7/3). And the water contact angle of PMPC brush increased after block polymerization of GMA. These results indicated that GMA could be polymerized from PMPC brushes. GMA can immobilize biomolecules such as protein, offering effective surface for biosensing.

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  • Design of well-defined hydrogels by nanogel engineering

    Nobuyuki Morimoto, Takafumi Ohki, Kimio Kurita, Yasuhiko Iwasaki, Kazunari Akiyoshi

    Polymer Preprints, Japan   54 ( 2 )   4731 - 4732   2005

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    We develop tailor-made functional nanogels to create novel nanobiomaterials (nanogel engineering) by self-assembling of functional associating polymers as building blocks. Self-assembled nanogels containing polymerizable groups (nanogelomers) were designed as key building blocks. Hybrid hydrogels were prepared by copolymerization of the nanogelomers in the presence or absence of 2-methacryloyloxyethyl phosphorylcholine (MPC) in semi-dilute aqueous condition. CHPMA nanogelomers acted as a cross-linker and CHP-MPC hybrid hydrogels were prepared. The hydrogels spontaneously trapped proteins. By adding ß-CD solution, trapped proteins were released as native form. The hydrogels are now applied to the artificial molecular chaperone system. We can control the formation of well-defined nano-structured hydrogels by polymerization of methacryloyl group-bearing nanogels in their appropriate condition.

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  • Preparation of porous hydrogels cross-linked with poly(phosphoester) and their enzymatic degradation

    Yasuhiko Iwasaki, Chookaet Wachiralarpphaithoon, Kazunari Akiyoshi

    Polymer Preprints, Japan   54 ( 2 )   4937 - 4938   2005

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    Methacryloyl-functionalized polyphosphate (PIOP) was synthesized by ring-opening polymerization of 2-i-propyl-2-oxo-1,3,2-dioxaphospholane with 2-(2-oxo-1,3,2-dioxaphosphoroyloxyethyl methacrylate) (OPEMA). The number averaged molecular weight of the PIOP and the number of OPEMA unit in one PIOP chain were 1.2 × 10 4 and 2.2, respectively. The poly [2-methacryloyloxyethyl phosphorylcholine (MPC)] cross-linked with the PIOP was prepared by radical polymerization. The porosities of the hydrogels were controlled by salt-eluting or gas-forming processes. They influenced on mechanical properties of hydrogels, but not on degradability. The enzymatic degradation of the hydrogels was determined by soaking them into alkaline phosphatatase solution. The degradation rate of the hydrogels was significantly increased in the presence of ALP. MC3T3-E1 cells were incorporated into the porous hydrogels. Their morphology and viability of cells were observed by fluorescence microscope.

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  • Antithrombogenic polymer alloy containing phospholipid polymer

    Ishihara K, Ogawa R, Hasegawa T, Nishiuchi D, Watanabe J, Iwasaki Y

    2004.12

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    <p>Various features of antithrombogenic polymer alloy containing phospholipid polymers were investigated. Surface analysis of the polymer alloy membranes with X-ray photoelectron spectroscopy (XPS) revealed that the 2-methacryloyloxyethyl phosphorylcholine (MPC) unit was located at the surface of the polymer alloy membranes even when the composition of the MPC polymer was below 10wt%. Blending of the antithrombogenic MPC polymer in the conventional polymer(polymer alloy) was suggested to be a good way to obtain new polymer biomaterials for making artificial organs. It was observed that the polymer alloys does not show any adverse effect about the mechanical and thermal properties compared with the original conventional polymers.</p>

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  • A water-soluble phospholipid polymer as a new biocompatible synthetic DNA carrier Reviewed

    Sakaki, S, Tsuchida, M, Iwasaki, Y, Ishihara, K

    Bulletin of the Chemical Society of Japan   77 ( 12 )   2004

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    DOI: 10.1246/bcsj.77.2283

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  • Novel biodegradable polyphosphate cross-linker for making biocompatible hydrogel Reviewed

    Iwasaki, Y, Nakagawa, C, Ohtomi, M, Ishihara, K, Akiyoshi, K

    Biomacromolecules   5 ( 3 )   2004

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    DOI: 10.1021/bm049961m

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  • Nano-scale surface modification of a segmented polyurethane with a phospholipid polymer Reviewed

    Morimoto, N, Watanabe, A, Iwasaki, Y, Akiyoshi, K, Ishihara, K

    Biomaterials   25 ( 23 )   2004

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    DOI: 10.1016/j.biomaterials.2003.12.047

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  • Improved wet-bonding of MMA-TBB resin to dentin etched by 10% phosphoric acid in the presence of ferric ions Reviewed

    Iwasaki Y, Toida T, Nakabayashi N

    J Biomed Mater Res   68A:566-572   566 - 572   2004

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  • Innovative gas injection technique for closed-hollow obturator Reviewed

    Iramaneerat, W, Seki, F, Watanabe, A, Mukohyama, H, Iwasaki, Y, Akiyoshi, K, Taniguchi, H

    International Journal of Prosthodontics   17 ( 3 )   2004

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  • Polymer alloy composed polyethylene and phospholipids polymer as green biomaterials Reviewed

    Ishihara K, Nishiuchi D, Watanabe J, Iwasaki Y

    Biomaterials   25:1115-1122   2004

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  • Control of nanobiointerfaces generated from well-defined biomimetic polymer brushes for protein and cell manipulations Reviewed

    Iwata, R, Suk-In, P, Hoven, VP, Takahara, A, Akiyoshi, K, Iwasaki, Y

    Biomacromolecules   5 ( 6 )   2004

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    DOI: 10.1021/bm049613k

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  • Design of biodegradable amphiphilic polymers: Well-defined amphiphilic polyphosphates with hydrophilic graft chains via ATRP Reviewed

    Iwasaki, Y, Akiyoshi, K

    Macromolecules   37 ( 20 )   2004

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    DOI: 10.1021/ma049043g

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  • Copolymers of 2-methacryloyloxyethyl phosphorylcholine (MPC) as biomaterials Reviewed

    Nakabayashi, N, Iwasaki, Y

    Bio-Medical Materials and Engineering   14 ( 4 )   2004

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  • Effect of remaining demineralised dentine on dental microleakage accessed by a dye penetration: how to inhibit microleakage? Reviewed

    Piemjai, M, Watanabe, A, Iwasaki, Y, Nakabayashi, N

    Journal of Dentistry   32 ( 6 )   2004

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    DOI: 10.1016/j.jdent.2004.03.005

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  • Preparation of blood compatible surface by surface-initiated polymerization of 2-methacryloyloxyethyl phosphorylcholine Reviewed

    Hoven, VP, Suk-In, P, Srinanthakul, M, Kiatkamjornwong, S, Iwasaki, Y

    Abstracts of Papers of the American Chemical Society   227   2004

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  • Polyethylene/phospholipid polymer alloy as an alternative to poly(vinylchloride)-based materials Reviewed

    Ishihara, K, Nishiuchi, D, Watanabe, J, Iwasaki, Y

    Biomaterials   25 ( 6 )   2004

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    DOI: 10.1016/S0142-9612(03)00624-0

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  • Improved wet bonding of methyl methacrylate-tri-n-butylborane resin to dentin etched with ten percent phosphoric acid in the presence of ferric ions Reviewed

    Iwasaki, Y, Toida, T, Nakabayashi, N

    Journal of Biomedical Materials Research Part a   68A ( 3 )   2004

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    DOI: 10.1002/jbm.a..20106

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  • Biodegradable polymer micelle: Design of well-defined amphiphilic polyphosphate with hydrophilic graft chain via ATRP. Reviewed

    Iwasaki, Y, Akiyoshi, K

    Abstracts of Papers of the American Chemical Society   228   2004

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  • Reduced adhesion of blood cells to biodegradable polymers by introducing phosphorylcholine moieties Reviewed

    Iwasaki, Y, Tojo, Y, Kurosaki, T, Nakabayashi, N

    Journal of Biomedical Materials Research Part a   65A ( 2 )   2003

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    DOI: 10.1002/jbm.a.10459

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  • Controlled adhesion of human lymphocytes on electrically charged polymer surface having phosphorylcholine moiety

    Tomomi Ito, Yasuhiko Iwasaki, Tadashi Narita, Kazunari Akiyoshi, Kazuhiko Ishihara

    SCIENCE AND TECHNOLOGY OF ADVANCED MATERIALS   4 ( 2 )   99 - 104   2003

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    The human lymphocytes were interacted with polymer surfaces whose surface potential was controlled by the formation of a polyion complex (PIC) having a phosphorylcholine moiety. 3-(Methacryloyloxypropyl)-trimethyl ammonium iodide as the cationic unit or potassium 3-methacryloyloxypropyl sulfonate as the anionic unit was copolymerized with 2-methacryloyloxyethyl phosphorylcholine (MPC) and n-butyl methacrylate. PIC was made at the solid-liquid interface, that is, an aqueous solution containing an anionic polymer with different concentrations was contacted with a cationic polymer coated polymer membrane. The formation process of PIC was followed using a quartz crystal microbalance, and the PIC surfaces were analyzed by zeta-potential and X-ray photoelectron spectroscopy. The surface potential on the PIC was controllable from +20 to -16 mV, which increased in the amount of adsorbed anionic copolymer as the zeta-potential decreased toward the negative charge. The PIC surface in contact with human lymphocyte for 5 h was observed using a scanning electron microscopy and the density of the adherent human lymphocyte was determined by the lactate dehydrogenase method. The lymphocyte adhesion on the surface was gradually reduced with an increase in the negative value of the zeta-potential. The morphological change in the adherent lymphocytes was not observed on the polymer surfaces with MPC units. The adherent lymphocytes were not activated on the PIC surface. The lymphocyte adhesion with reduced activation could be controlled by changing the surface potential on the polymer with the MPC unit. (C) 2003 Elsevier Science Ltd. All rights reserved.

    DOI: 10.1016/S1468-6996(03)00014-7

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  • Biodegradable phosphorylcholine-hydrogel consist of polyphosphate cross-linking reagents Reviewed

    Iwasaki Y, Komatsu S, Narita T, Ishihara K, Akiyoshi K

    Macromol Biosci   3, 238-242   2003

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  • Influence of dentinal polyelectrolytes on dry and wet bonding to conditioned dentin Reviewed

    Piemjai M, Iwasaki Y, Nakabayashi N

    J Biomed Mater Res   66A:789-794   2003

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  • Synthesis and characterization of PLLA-based biodegradable polymer having a phospholipid polar group Reviewed

    Iwasaki Y, Tojo Y, Kurosaki T

    J Biomed Mater Res   65A:164-169   164 - 169   2003

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  • Suppression of the inflammatory response from adherent cells on phospholipid polymers Reviewed

    Sawada, S, Sakaki, S, Iwasaki, Y, Nakabayashi, N, Ishihara, K

    Journal of Biomedical Materials Research Part a   64A ( 3 )   2003

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    DOI: 10.1002/jbm.a.10433

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  • Surface mobility of polymers having phosphorylcholine groups connected with various bridging units and their protein adsorption-resistance properties Reviewed

    Yamasaki, A, Imamura, Y, Kurita, K, Iwasaki, Y, Nakabayashi, N, Ishihara, K

    Colloids and Surfaces B-Biointerfaces   28 ( 1 )   2003

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  • Hydrogel-like elastic membrane consisting of semi-interpenetrating polymer networks based on a phosphorylcholine polymer and a segmented polyurethane Reviewed

    Iwasaki, Y, Shimakata, K, Morimoto, N, Kurita, K

    Journal of Polymer Science Part a-Polymer Chemistry   41 ( 1 )   2003

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    DOI: 10.1002/pola.10554

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  • Nonthrombogenic hemodialyzer with MPC copolymer Reviewed

    Iwasaki Y, Nakabayashi N, Ishihara K

    Advances in Science and Technology   41(Materials in Clinical Applications VI):161-170   2003

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  • Improvement of platelet compatibility of blood filtration devices with a phospholipid polymer having high surface mobility Reviewed

    Iwasaki Y, Yamasaki A, Ishihara K

    Biomaterials   24, 3599-3604   3599 - 3604   2003

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  • Frictional properties of poly(MPC-co-BMA) phospholipid polymer for catheter applications Reviewed

    Ho, SP, Nakabayashi, N, Iwasaki, Y, Boland, T, LaBerge, M

    Biomaterials   24 ( 28 )   2003

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    DOI: 10.1016/S0142-9612(03)00450-2

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  • Bioinspired polymer surfaces for prevention of bioresponse Reviewed

    Ishihara, K, Watanabe, J, Iwasaki, Y, Chandra, T, Torralba, JM, Sakai, T

    426-4   2003

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  • Biodegradable phosphorylcholine polymer hydrogels cross-linked with vinyl-functionalized polyphosphate Reviewed

    Iwasaki, Y, Komatsu, S, Narita, T, Akiyoshi, K, Ishihara, K

    Macromolecular Bioscience   3 ( 5 )   2003

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    DOI: 10.1002/mabi.200390031

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  • Biocompatible polymer alloy with phospholipid polymer as green biomaterials. Reviewed

    Ishihara, K, Nishiuchi, D, Watanabe, J, Iwasaki, Y

    Abstracts of Papers of the American Chemical Society   226   2003

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  • In vitro and ex vivo blood compatibility study of 2-methacryloyloxyethyl phosphorylcholine (MPC) copolymer-coated hemodialysis hollow fibers Reviewed

    Iwasaki, Y., Nakabayashi, N., Ishihara, K.

    J Artif Organs   6 ( 4 )   2003

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    DOI: 10.1007/s10047-003-0234-8

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  • Nanofrictional properties of poly(MPC-co-BMA) phospholipid polymer for biomaterials application Reviewed

    Ho SP, Nakabayashi N, Iwasaki Y, Boland T, LaBerge M

    Biomaterials   24:5121-5129   5121 - 5129   2003

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  • Chemically adsorption of phosphorylcholine polymers to Ti-supported vinyldimethylsilyl monolayers and reduction of albumin adsorption Reviewed

    Iwasaki Y, Saito N

    Colloid & surface B, Biointerface   32:77-84   2003

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  • Antifouling blood purification membrane composed of cellulose acetate and phospholipid polymer Reviewed

    Ye, SH, Watanabe, J, Iwasaki, Y, Ishihara, K

    Biomaterials   24 ( 23 )   2003

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    DOI: 10.1016/S0142-9612(03)00296-5

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  • Platelet compatible blood filtration fabrics using a phosphorylcholine polymer having high surface mobility Reviewed

    Iwasaki, Y, Yamasaki, A, Ishihara, K

    Biomaterials   24 ( 20 )   2003

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    DOI: 10.1016/S0142-9612(03)00212-6

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  • Influence of dentinal polyelectrolytes on wet demineralized dentin, a bonding substrate Reviewed

    Piemjai, M, Iwasaki, Y, Nakabayashi, N

    Journal of Biomedical Materials Research Part a   66A ( 4 )   2003

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    DOI: 10.1002/jbm.a.10572

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  • Immobilization of phosphorylcholine polymers to Ti-supported vinyldimethylsilyl monolayers and reduction of albumin adsorption Reviewed

    Iwasaki, Y, Saito, N

    Colloids and Surfaces B-Biointerfaces   32 ( 1 )   2003

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    DOI: 10.1016/S0927-7765(03)00147-4

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  • Synthesis of vinyl-functionalized polyphosphate and preparation of the biodegradable hydrogel with 2-methacryloyloxyethyl phosphorylcholine. Reviewed

    Iwasaki, Y, Nakagawa, C, Komatsu, S, Akiyoshi, K, Ishihara, K

    Abstracts of Papers of the American Chemical Society   226   2003

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  • Reduction of surface-induced inflammatory reaction on PLGA/MPC polymer blend Reviewed

    Iwasaki, Y, Sawada, S, Ishihara, K, Khang, G, Lee, HB

    Biomaterials   23 ( 18 )   2002

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    DOI: 10.1016/S0142-9612(02)00135-7

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  • The vascular prosthesis without pseudointima prepared by anti thrombogenic phospholipid polymer Reviewed

    Yoneyama, T, Sugihara, K, Ishihara, K, Iwasaki, Y, Nakabayashi, N

    Biomaterials   23 ( 6 )   2002

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    DOI: 10.1016/S0142-9612(01)00268-X

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  • Protein adsorption-resistant hollow fibers for blood purification Reviewed

    Ishihara, K, Hasegawa, T, Watanabe, J, Iwasaki, Y

    Artificial Organs   26 ( 12 )   2002

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    DOI: 10.1046/j.1525-1594.2002.07039.x

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  • Novel cellulose acetate membrane blended with phospholipid polymer for hemocompatible filtration system Reviewed

    Ye, SH, Watanabe, J, Iwasaki, Y, Ishihara, K

    Journal of Membrane Science   210 ( 2 )   2002

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  • Comparison of microleakage of three acid-base luting cements versus one resin-bonded cement for Class V direct composite inlays Reviewed

    Piemjai, M, Miyasaka, K, Iwasaki, Y, Nkaabayashi, N

    Journal of Prosthetic Dentistry   88 ( 6 )   2002

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    DOI: 10.1067/mpr.2002.129383

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  • Physical properties and blood compatibility of surface-modified segmented polyurethane by semi-interpenetrating polymer networks with a phospholipid polymer Reviewed

    Morimoto, N, Iwasaki, Y, Nakabayashi, N, Ishihara, K

    Biomaterials   23 ( 24 )   2002

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    DOI: 10.1016/S0142-9612(02)00246-6

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  • Coating stability and blood compatibility of stainless steel surface modified with phospholipid polymer Reviewed

    Morimoto, N, Sato, I, Watanabe, A, Nakabayashi, N, Iwasaki, Y, Ishihara, K

    Kobunshi Ronbunshu   59 ( 7 )   2002

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  • Stabilized liposomes with phospholipid polymers and their interactions with blood cells Reviewed

    Ishihara, K, Tsujino, R, Mika, H, Toyoda, N, Iwasaki, Y

    Colloids and Surfaces B-Biointerfaces   25 ( 4 )   2002

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    DOI: 10.1016/S0927-7765(02)00006-1

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  • Thermal property and processability of elastomeric polymer alloy composed of segmented polyurethane and phospholipid polymer Reviewed

    Ogawa, R, Iwasaki, Y, Ishihara, K

    Journal of Biomedical Materials Research   62 ( 2 )   2002

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    DOI: 10.1002/jbm.10339

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  • A nonthrombogenic gas-permeable membrane composed of a phospholipid polymer skin film adhered to a polyethylene porous membrane Reviewed

    Iwasaki, Y, Uchiyama, S, Kurita, K, Morimoto, N, Nakabayashi, N

    Biomaterials   23 ( 16 )   2002

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  • Preparation of blood-compatible hollow fibers from a polymer alloy composed of polysulfone and 2-methacryloyloxyethyl phosphorylcholine polymer Reviewed

    Hasegawa, T, Iwasaki, Y, Ishihara, K

    Journal of Biomedical Materials Research   63 ( 3 )   2002

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    DOI: 10.1002/jbm.10210

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  • Importance of a biofouling-resistant phospholipid polymer to create a heparinized blood-compatible surface Reviewed

    Iwasaki, Y, Shibata, N, Ninomiya, M, Kurita, K, Nakabayashi, N, Ishihara, K

    Journal of Biomaterials Science-Polymer Edition   13 ( 3 )   2002

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  • Improving a self-curing dental resin by eliminating oxygen, hydroquinone and water from its curing process Reviewed

    Keh, ES, Hayakawa, I, Takahashi, H, Watanabe, A, Iwasaki, Y, Akiyoshi, K, Nakabayashi, N

    Dental Materials Journal   21 ( 4 )   2002

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  • Coating stability and blood compatibility of stainless steel surface modified with phospholipid polymer Reviewed

    Nobuyuki Morimoto, Ikue Sato, Akihiko Watanabe, Nobuo Nakabayashi, Yasuhiko Iwasaki, Kazuhiko Ishihara

    Kobunshi Ronbunshu   59 ( 7 )   432 - 437   2002

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    To improve the blood compatibility of the surface of stainless steel, which is used as a base material of stent for cardiovascular treatment, the surface was coated with a 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer. 4-Methacryloyloxyethyl trimellitate anhydride (4-META)/methyl methacrylate (MMA) polymer was precoated on the stainless steel plate as a binder to obtain the long term stability of the MPC polymer. The surface of modified stainless steel was analyzed with XPS. The amount of the polymer eluted from the surfaces was evaluated by soaking samples in water for 14 days at 37°C. All of MPC polymer directly coated on stainless plate was eluted after 14 days soaking. On the other hand, the elution of the MPC polymer was significantly reduced by precoating of 4-META/MMA polymer on stainless plate. This surface effectively reduced protein adsorption and platelet adhesion. MPC polymer coated with 4-META/MMA polymer on stainless steel will be a useful technique as surface modification of the stent.

    DOI: 10.1295/koron.59.432

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  • Preparation of performance of protein adsorption resistance asymmetric porous membrane by polysulfone/phospholipid polymer blend Reviewed

    Hasegawa T, Iwasaki Y, Ishihara K

    Biomaterials   22(3):243-251   2001

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  • Ultrahydrophilic monolayers generated from vinylsilanes attached to silicon: Evaluation of surface properties and biofouling. Reviewed

    Iwasaki, Y, McCarthy, TJ

    Abstracts of Papers of the American Chemical Society   222   2001

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  • Preparation of nanoparticles composed with bioinspired 2-methacryloyloxyethyl phosphorylcholine polymer Reviewed

    Konno, T, Kurita, K, Iwasaki, Y, Nakabayashi, N, Ishihara, K

    Biomaterials   22 ( 13 )   2001

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    DOI: 10.1016/S0142-9612(00)00373-2

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  • Preparation and performance of protein-adsorption-resistant asymmetric porous membrane composed of polysulfone/phospholipid polymer blend Reviewed

    Hasegawa, T, Iwasaki, Y, Ishihara, K

    Biomaterials   22 ( 3 )   2001

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    DOI: 10.1016/S0142-9612(00)00180-0

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  • Molecular design and preparation of bioinspired phospholipid polymer as novel biomaterials. Reviewed

    Ishihara, K, Iwasaki, Y

    Abstracts of Papers of the American Chemical Society   222   2001

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  • Effect of semi-IPN modification of phospholipid polymer on physical properties and biocompatibility of segmented polyurethane. Reviewed

    Iwasaki, Y, Morimoto, N, Ishihara, K

    Abstracts of Papers of the American Chemical Society   222   2001

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  • Preservation of platelet function on 2-methacryloyloxyethyl phosphorylcholine-graft polymer as compared to various water-soluble graft polymers Reviewed

    Iwasaki, Y, Nakabayashi, N, Ishihara, K

    Journal of Biomedical Materials Research   57 ( 1 )   2001

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  • Biocompatibility of poly(MPC-co-EHMA)/poly(L-lactide-co-glycolide) blends Reviewed

    Khang, G, Choi, MK, Rhee, JM, Lee, SJ, Lee, HB, Iwasaki, Y, Nakabayashi, N, Ishihara, K

    Korea Polymer Journal   9 ( 2 )   2001

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  • Synthesis of novel phospholipid polymers by polycondensation Reviewed

    Iwasaki, Y, Nakabayashi, N, Ishihara, K

    Macromolecular Rapid Communications   21 ( 6 )   2000

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  • Antithrombogenic polymer alloy composed of 2-methacryloyloxyethyl phosphorylcholine polymer and segmented polyurethane Reviewed

    Ishihara, K, Fujita, H, Yoneyama, T, Iwasaki, Y

    Journal of Biomaterials Science-Polymer Edition   11 ( 11 )   2000

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  • Water-soluble 2-methacryloyloxyethyl phosphorylcholine copolymer as a novel synthetic blocking reagent in immunoassay system Reviewed

    Sakaki, S, Iwasaki, Y, Nakabayashi, N, Ishihara, K

    Polymer Journal   32 ( 8 )   2000

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  • Semi-interpenetrating polymer networks composed of biocompatible phospholipid polymer and segmented polyurethane Reviewed

    Iwasaki, Y, Aiba, Y, Morimoto, N, Nakabayashi, N, Ishihara, K

    Journal of Biomedical Materials Research   52 ( 4 )   2000

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  • Photoinduced graft polymerization of 2-methacryloyloxyethyl phosphorylcholine on polyethylene membrane surface for obtaining blood cell adhesion resistance Reviewed

    Ishihara, K, Iwasaki, Y, Ebihara, S, Shindo, Y, Nakabayashi, N

    Colloids and Surfaces B-Biointerfaces   18 ( 3-4 )   2000

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    DOI: 10.1016/S0927-7765(99)00158-7

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  • Biocompatible elastomers composed of segmented polyurethane and 2-methacryloyloxyethyl phosphorylcholine polymer Reviewed

    Ishihara, K, Iwasaki, Y

    Polymers For Advanced Technologies   11 ( 8-12 )   2000

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  • Phospholipid polymer biomaterials for making ventricular assist devices Reviewed

    Ishihara, K., Iwasaki, Y., Nojiri, C.

    Journal of Congestive Heart Failure and Circulatory Support   1 ( 4 )   2000

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  • Artificial Material (organic)

    IWASAKI Yasuhiko

    Journal of the Japanese Society for Artificial Organs and Tissues   28 ( 5 )   670 - 672   1999.12

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    Language:Japanese   Publisher:JAPANESE SOCIETY FOR ARTIFICIAL ORGANS  

    DOI: 10.11392/jsao1972.28.670

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  • Behavior of blood cells in contact with water-soluble phospholipid polymer Reviewed

    Iwasaki, Y, Ijuin, M, Mikami, A, Nakabayashi, N, Ishihara, K

    Journal of Biomedical Materials Research   46 ( 3 )   1999

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  • Poly(L-lactic acid) nanoparticles covered with the phospholipid polymer with excellent biocompatibility Reviewed

    Konno T, Kurita K, Iwasaki Y, Nakabayashi N, Ishihara K

    R P P J   42:463-466   1999

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  • Inhibition of fibroblast cell adhesion on substrate by coating with 2-methacryloyloxyethyl phosphorylcholine polymers Reviewed

    Ishihara, K, Ishikawa, E, Iwasaki, Y, Nakabayashi, N

    Journal of Biomaterials Science-Polymer Edition   10 ( 10 )   1999

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    DOI: 10.1163/156856299X00676

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  • The effect of the chemical structure of the phospholipid polymer on fibronectin adsorption and fibroblast adhesion on the gradient phospholipid surface Reviewed

    Iwasaki, Y, Sawada, S, Nakabayashi, N, Khang, G, Lee, HB, Ishihara, K

    Biomaterials   20 ( 22 )   1999

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    DOI: 10.1016/S0142-9612(99)00123-4

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  • Modification of polysulfone with phospholipid polymer for improvement of the blood compatibility. Part 2. Protein adsorption and platelet adhesion Reviewed

    Ishihara, K, Fukumoto, K, Iwasaki, Y, Nakabayashi, N

    Biomaterials   20 ( 17 )   1999

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    DOI: 10.1016/S0142-9612(98)00206-3

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  • Modification of polysulfone with phospholipid polymer for improvement of the blood compatibility. Part 1. Surface characterization Reviewed

    Ishihara, K, Fukumoto, K, Iwasaki, Y, Nakabayashi, N

    Biomaterials   20 ( 17 )   1999

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    DOI: 10.1016/S0142-9612(99)00052-6

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  • Competitive adsorption between phospholipid and plasma protein on a phospholipid polymer surface) Reviewed

    Iwasaki, Y., Nakabayashi, N., Nakatani, M., Mihara, T., Kurita, K., Ishihara, K.

    Journal of Biomaterials Science, Polymer Edition   10 ( 5 )   1999

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    DOI: 10.1163/156856299X00450

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  • Improvement of blood compatibility on cellulose hemodialysis membrane: IV. Phospholipid polymer bonded to the membrane surface Reviewed

    Ishihara, K, Shinozuka, T, Hanazaki, Y, Iwasaki, Y, Nakabayashi, N

    Journal of Biomaterials Science-Polymer Edition   10 ( 3 )   1999

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    DOI: 10.1163/156856299X00342

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  • Preparation of blood compatible nanoparticles bearing phospholipid polar group as a novel drug carrier Reviewed

    Konno, T., Kurita, K., Iwasaki, Y., Nakabayashi, N., Ishihara, K.

    Proceedings of the Controlled Release Society   22:1883-1889 ( 26 )   1999

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  • Polymeric lipid nanosphere consisting of water-soluble poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) Reviewed

    Ishihara, K, Iwasaki, Y, Nakabayashi, N

    Polymer Journal   31 ( 12 )   1999

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  • Drug release from segmented polyurethane containing blood compatible phospholipid polymer as a polymeric additive Reviewed

    Ishihara, K., Iwasaki, Y.

    Proceedings of the Controlled Release Society   ( 26 )   114 - 115   1999

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  • Preparation of blood compatible nanoparticles bearing phosphorylcholine group. Reviewed

    Ishihara, K, Konno, T, Kurita, K, Iwasaki, Y, Nakabayashi, N

    Abstracts of Papers of the American Chemical Society   217   1999

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    Publishing type:Research paper (scientific journal)   Publisher:ACS Symposium Series  

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  • Water-soluble phospholipid polymers as novel synthetic blocking agent. Reviewed

    Ishihara, K, Iwasaki, Y, Sakaki, S, Nakabayashi, N

    Abstracts of Papers of the American Chemical Society   216   1998

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  • Reduced protein adsorption on novel phospholipid polymers Reviewed

    Ishihara, K, Iwasaki, Y

    Journal of Biomaterials Applications   13 ( 2 )   1998

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1177/088532829801300203

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  • Platelet adhesion on the gradient surfaces grafted with phospholipid polymer Reviewed

    Iwasaki, Y, Ishihara, K, Nakabayashi, N, Khang, G, Jeon, JH, Lee, JW, Lee, HB

    Journal of Biomaterials Science-Polymer Edition   9 ( 8 )   1998

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    DOI: 10.1163/156856298X00163

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  • Novel biomedical polymers for regulating serious biological reactions Reviewed

    Ishihara, K, Iwasaki, Y, Nakabayashi, N

    Materials Science &amp; Engineering C-Biomimetic and Supramolecular Systems   6 ( 4 )   1998

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/S0928-4931(98)00059-9

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  • Blood compatibility of cellulose hemodialysis membrane grafted with various polymers Reviewed

    Kawano, H, Kurita, K, Iwasaki, Y, Ishihara, K, Nakabayashi, N

    Kobunshi Ronbunshu   55 ( 6 )   1998

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  • Design of enzymatic glucose sensor by using biocompatible polymeric mediator Reviewed

    Saito, T, Kurosawa, N, Watanabe, M, Iwasaki, Y, Ishihara, K

    Kobunshi Ronbunshu   55 ( 4 )   1998

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  • Surface grafting of phospholipid polymer on cellulose membrane for improving hemocompatibility Reviewed

    Kawano H, Kurita K, Iwasaki Y, Nakabayashi N

    R P P J   41, 305-308   1998

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  • Why do phospholipid polymers reduce protein adsorption? Reviewed

    Ishihara, K, Nomura, H, Mihara, T, Kurita, K, Iwasaki, Y, Nakabayashi, N

    Journal of Biomedical Materials Research   39 ( 2 )   1998

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/(SICI)1097-4636(199802)39:2<323::AID-JBM21>3.0.CO;2-C

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  • Reduction of surface-induced platelet activation on phospholipid polymer Reviewed

    Iwasaki, Y, Mikami, A, Kurita, K, Yui, N, Ishihara, K, Nakabayashi, N

    Journal of Biomedical Materials Research   36 ( 4 )   1997

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/(SICI)1097-4636(19970915)36:4<508::AID-JBM8>3.0.CO;2-I

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  • Evaluation of the frictional properties of an elastomer with enhanced lipid-adsorbing ability Reviewed

    Williams, PF, Iwasaki, Y, Ishihara, K, Powell, GL, Gilbert, JA, Nakabayashi, N, LaBerge, M

    Proceedings of the Institution of Mechanical Engineers Part H-Journal of Engineering in Medicine   211 ( 5 )   1997

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  • Stabilization of liposomes attached to polymer surfaces having phosphorylcholine groups Reviewed

    Iwasaki, Y, Tanaka, S, Hara, M, Ishihara, K, Nakabayashi, N

    Journal of Colloid and Interface Science   192 ( 2 )   1997

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  • In vitro evaluation of the ability of a phospholipid polymer to reduce fibroblast attachment

    Newton B, Watanabe A, Iwasaki Y, Williams P. F, Gilbert J. A, LaBerge M, Ishihara K, Nakabayashi N

    1996.12

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    <p>Research was conducted to determine if semi-interpenetrating polymer network (sIPN) surface formation, using a crosslinked MPC copolymer, is an effective method to produce a stable surface treatment. The materials' ability to suppress fibroblast attachment was also investigated. Four materials were fabricated and tested: solution cast Tecoflex SG93A; a solution cast blend of Tecoflex and 7.5 wt.% Mpc(30 mol%)-co-cyclohexyl methacrylate (CHMA); a solution cast blend of Tecoflex and 7.5 wt.% MPC(30 mol%)-co-2-ethylexyl methacrylate (EHMA); and a sequential surface sPIN. Examination by scanning electron microscopy (SEM) revealed that sIPN produced the best results with no cell attachment visible on the material surface.</p>

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  • Synthetic endothelial surface with phospholipid polymer

    Iwasaki Y, Ishihara K, Nakabayashi N

    1996.12

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    <p>Phospholipid polymers with various poly(oxyethylene) were synthesized and their phospholipid adsorption, protein adsorption, and platelet adhesion were studied. The polymer containing 30mol% phospholipid moiety suppressed platelet adhesion. On the methacryloyloxyalkyl phosphorylcholines (MAPC) copolymer with 10mol% MAPC composition, the number of platelet decreased with an increase in the length of methylene chain because of the increase of affinity to phospholipid while on MEOnPC copolymer, the number of platelet increased with the increased in oxyethylene chain length. The MAPC polymers with 2 to 6 methylene chain length have good blood compatible materials.</p>

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  • Protein adsorption and platelet adhesion on polymer surfaces having phospholipid polar group connected with oxyethylene chain Reviewed

    Iwasaki, Y, Fujiike, A, Kurita, K, Ishihara, K, Nakabayashi, N

    Journal of Biomaterials Science-Polymer Edition   8 ( 2 )   1996

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  • Improved blood compatibility of segmented polyurethane by polymeric additives having phospholipid polar group. II. Dispersion state of the polymeric additive and protein adsorption on the surface Reviewed

    Ishihara, K., Shibata, N., Tanaka, S., Iwasaki, Y., Kurosaki, T., Nakabayashi, N.

    Journal of Biomedical Materials Research   32 ( 3 )   1996

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  • Synthesis of polymers having a phospholipid polar group connected to a poly(oxyethylene) chain and their protein adsorption-resistance properties Reviewed

    Ishihara, K, Fujiike, A, Iwasaki, Y, Kurita, K, Nakabayashi, N

    Journal of Polymer Science Part a-Polymer Chemistry   34 ( 2 )   1996

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  • Effect of reduced protein adsorption on platelet adhesion at the phospholipid polymer surfaces Reviewed

    Iwasaki, Y, Kurita, K, Ishihara, K, Nakabayashi, N

    Journal of Biomaterials Science-Polymer Edition   8 ( 2 )   1996

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1163/156856296X00228

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  • New Blood Compatible Materials for Treatment on the Surface of Biomedical Device

    IWASAKI Yasuhiko, ISHIHARA Kazuhiko, NAKABAYASHI Nobuo

    Jitsumu Hyomen Gijutsu   46 ( 10 )   880 - 886   1995.10

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    Language:Japanese   Publisher:The Surface Finishing Society of Japan  

    DOI: 10.4139/sfj.46.880

    CiNii Books

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    Other Link: https://jlc.jst.go.jp/DN/JALC/00081979998?from=CiNii

  • Effect of methylene chain length in phospholipid moiety on blood compatibility of phospholipid polymers Reviewed

    Iwasaki, Y., Kurita, K., Ishihara, K., Nakabayashi, N.

    Journal of Biomaterials Science, Polymer Edition   6 ( 5 )   1995

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1163/156856294X00437

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  • Ex vivo blood compatibility of polymers having phospholipid polar group Reviewed

    Yasuhiko Iwasaki

    J. Jpn. Soc. Biomater.   13, 62-70   1995

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  • Assessment of adsorption of liposomes on a phospholipid polymer surface using a quartz crystal microbalance Reviewed

    Tanaka, S., Iwasaki, Y., Ishihara, K., Nakabayashi, N.

    Macromolecular Rapid Communications   15 ( 4 )   1994

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/marc.1994.030150404

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  • Polyphosphoester/tannic acid composite sticky coacervates as adhesives

    Cheng, Yichen, Ueda, Masato, Iwasaki, Yasuhiko

    Chemistry Letters   1970.1

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1246/cl.220217

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Books

  • PCサーフェイステクノロジー,最新透析医学

    岩崎泰彦, 西沢良記編( Role: Sole author)

    最新透析医学,医薬ジャーナル社  2008 

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  • 高密度ポリマーブラシ界面

    岩崎泰彦, 秋吉一成編, 岸田晶夫編( Role: Sole author)

    次世代医療のための高分子材料工学,シーエムシー出版  2008 

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MISC

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Presentations

  • Modification of glass surface by biocompatible polymer

    Honda T, Yusa S, Ishihara K, Iwasaki Y

    The 11th SPSJ International Polymer Conference (IPC 2016)  2016.12 

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    Venue:Fukuoka  

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  • Zwitterion-protected silver nano clusters having antibacterial activity and biocompatibility

    Sangsuwan A, Kawasaki H, Matsumura Y, Iwasaki Y

    The 11th SPSJ International Polymer Conference (IPC 2016)  2016.12 

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    Venue:Fukuoka  

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  • Binding affinity of poly(ethylene phosphate) nanoparticles to bone

    Hirano Y, Hongou H, Iwasaki Y

    The 11th SPSJ International Polymer Conference (IPC 2016)  2016.12 

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    Venue:Fukuoka  

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  • Metabolic expression of methacryloyl groups on cell surface carbohydrates

    Iwasaki Y, Sugimoto S, Mori T

    The 11th SPSJ International Polymer Conference (IPC 2016)  2016.12 

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    Venue:Fukuoka  

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  • リン脂質ポリマー被覆磁性粒子による C-反応性タンパク質の検出及び回収

    岩崎紗奈, 川崎英也, 岩﨑泰彦

    日本バイオマテリアル学会第5回北陸信越若手研究発表会  2016.12 

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    Venue:新潟  

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  • アポトーシス誘導したがん細胞の貪食を亢進する核酸アプタマー修飾マクロファージ

    杉本駿介, 森健, 岩﨑泰彦

    第26回日本MRS年次大会  2016.12 

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    Venue:横浜  

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  • Mineralization of PEEK surface for establishing biointegration

    Kunomura S, Iwasaki Y

    The 11th SPSJ International Polymer Conference (IPC 2016)  2016.12 

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    Venue:Fukuoka  

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  • 骨治療に向けたポリリン酸エステルの分子デザイン

    岩﨑泰彦

    日本バイオマテリアル学会シンポジウム2016  2016.11 

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    Venue:福岡  

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  • 低温成形可能な生分解性ブロックコポリマーに複合化されたタンパク質の活性

    岩﨑泰彦, 竹本恭平, 谷口育雄

    第65回高分子討論会  2016.9 

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    Venue:神奈川  

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  • 生体適合性ポリマーによるガラス基板へのタンパク質吸着の抑制

    本田智子, 遊佐真一, 石原一彦, 岩﨑泰彦

    第65回高分子討論会  2016.9 

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    Venue:神奈川  

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  • PMPC 被覆磁性粒子による C-反応性タンパク質の非標識検出

    岩崎紗奈, 岩﨑泰彦

    第65回高分子討論会  2016.9 

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    Venue:神奈川  

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  • アミノ酸残基を持つリン脂質ポリマー薄膜の光機能化

    田中雅子, 岩﨑泰彦

    第65回高分子討論会  2016.9 

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    Venue:神奈川  

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  • 糖鎖改変技術による免疫細胞の表面改質と細胞接着機能制御

    杉本駿介, 岩﨑泰彦, 森健

    第65回高分子討論会  2016.9 

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    Venue:神奈川  

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  • エラスチン様タンパクゲル上でのマウス iPS 細胞の心筋分化挙動

    徳重恭之, 神戸裕介, 馬原淳, 岩﨑泰彦, 山岡哲二

    日本バイオマテリアル学会第11回関西若手研究発表会  2016.8 

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    Venue:兵庫  

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  • バイオミネラリゼーションに倣う PEEK 表面の改質

    久野村駿, 岩﨑泰彦

    日本バイオマテリアル学会第11回関西若手研究発表会  2016.8 

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    Venue:兵庫  

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  • ポリリン酸エステルによる骨系細胞の機能制御

    井上直之, 中村美穂, 岩﨑泰彦

    日本バイオマテリアル学会第11回関西若手研究発表会  2016.8 

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    Venue:兵庫  

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  • 生体適合性ポリマーによるガラス基板の修飾

    本田智子, 遊佐真一, 石原一彦, 岩﨑泰彦

    第62回高分子研究発表会(神戸)  2016.7 

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    Venue:兵庫  

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  • ポリエチレンホスフェートによる PEEK 表面の生体活性化

    久野村駿, 岩﨑泰彦

    第62回高分子研究発表会(神戸)  2016.7 

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    Venue:兵庫  

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  • リン脂質ポリマーで表面保護した磁性粒子による C-反応性タンパク質の検出

    岩崎紗奈, 岩﨑泰彦

    第62回高分子研究発表会(神戸)  2016.7 

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    Venue:兵庫  

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  • マクロファージ指向性を示す細菌細胞壁模倣ナノ粒子

    平野佑弥, 岩﨑泰彦

    第45回医用高分子シンポジウム  2016.7 

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    Venue:東京  

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  • 核酸修飾マクロファージによるがん細胞捕捉とサイトカイン産生

    杉本駿介, 森健, 岩﨑泰彦

    第45回医用高分子シンポジウム  2016.7 

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    Venue:東京  

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  • 多孔質スキャホールド内部への組織誘導に及ぼす表面特性の影響

    山岡哲二, 安田裕貴, 神戸裕介, 岩﨑泰彦, 柿木佐知朗

    第45回医用高分子シンポジウム  2016.7 

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    Venue:東京  

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  • Myocardial differentiation of rat mesenchymal stem cells in elastin-like recombinant protein hydrogels

    Tokushige T, Kambe Y, Mahara A, Iwasaki Y, Yamaoka T

    10th World Biomaterials Congress  2016.5 

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    Venue:Canada  

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  • Preparation and characterization of polyphosphoester coated nanoparticles having a potential for delivery of hydrophobic drugs to bone

    Hirano Y, Iwasaki Y

    10th World Biomaterials Congress  2016.5 

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    Venue:Canada  

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  • Controlled photo-immobilization of proteins on phospholipid polymer surfaces

    Tanaka M, Iwasaki Y

    10th World Biomaterials Congress  2016.5 

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    Venue:Canada  

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  • Regulation of osteoclast function by poly(ethylene sodium phosphate)

    Iwasaki Y, Kootala S, Hilborn J

    10th World Biomaterials Congress  2016.5 

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    Venue:Canada  

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  • ポリエチレンホスフェートによる骨芽細胞の機能誘導

    井上直之, 岩﨑泰彦

    第65回 高分子年次大会  2016.5 

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    Venue:神戸国際会議場・展示場,兵庫  

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  • ポリリン酸エステルナノ粒子の骨の無機主成分に対する親和性に及ぼすpH の影響

    平野佑弥, 岩﨑泰彦

    第65回 高分子年次大会  2016.5 

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    Venue:神戸国際会議場・展示場,兵庫  

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  • 光反応性リン脂質ポリマーによる酵素機能界面の構築

    田中雅子, 岩﨑泰彦

    第65回 高分子年次大会  2016.5 

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    Venue:神戸国際会議場・展示場,兵庫  

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  • ラット間葉系幹細胞の心筋細胞分化誘導のためのエラスチン様リコンビナントタンパクゲルの開発

    徳重恭之, 神戸裕介, 馬原 淳, 岩﨑泰彦, 山岡哲二

    第65回 高分子年次大会  2016.5 

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    Venue:神戸国際会議場・展示場,兵庫  

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  • 骨組織適合型インプラントの創製に向けPEEKの表面改質

    久野村駿, 岩﨑泰彦

    第65回 高分子年次大会  2016.5 

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    Venue:神戸国際会議場・展示場,兵庫  

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  • Thiolated-2-methacryloyloxyethyl phosphorylcholine protected silver nanoparticles as novel photo-induced cell-killing agents

    Sangsuwan A, Kawasaki H, Iwasaki Y

    10th World Biomaterials Congress  2016.5 

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    Venue:Canada  

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  • Immobilization of nucleic acid aptamer on macrophages for circurating tumor cell capture

    Sugimoto S, Mori T, Iwasaki Y

    10th World Biomaterials Congress  2016.5 

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    Venue:Canada  

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  • Surface modification of PEEK for improving osteocompatibility

    Kunomura S, Iwasaki Y

    10th World Biomaterials Congress  2016.5 

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    Venue:Canada  

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  • メタクリロイル基の導入による細胞表面修飾技術

    岩﨑泰彦

    第65回 高分子年次大会  2016.5 

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    Venue:神戸国際会議場・展示場,兵庫  

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  • 膜工学サロン

    岩崎泰彦

    先端膜工学推進機構総会および春期講演会, 膜工学サロン  2009 

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  • 高密度ポリマーブラシに支持されたリン脂質吸着膜の調製と解析

    中井康介, 岩崎泰彦

    第57回高分子討論会講演予稿集  2008.9 

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  • ブロックポリマーブラシを表面修飾したシリコンナノ粒子の調製と発光特性

    柴田靖久, 岩﨑泰彦

    第57回高分子討論会講演予稿集  2008.9 

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  • 高分子ブラシを利用したバイオ集積界面の創製

    岩崎泰彦, 大道有紀, 岩田綾子

    第57回高分子討論会講演予稿集  2008.9 

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  • 生体適合性ポリマーで被覆したシリコンナノ粒子の調製

    柴田靖久, 岩崎泰彦

    第3回日本バイオマテリアル学会関西若手研究報告会要旨集  2008.8 

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  • 細胞膜表層に学ぶ生体機能高分子界面の構築と機能

    岩崎泰彦

    第54回高分子研究発表会(神戸)予稿集  2008.7 

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  • 刺激応答性ポリリン酸エステルの合成と特性

    岩崎泰彦, 河北 崇, 秋吉一成

    第37回医用高分子シンポジウム講演要旨集  2008.7 

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  • ポリマーブラシを用いたリン脂質二分子膜アレイの調製

    中井康介, 岩崎泰彦

    第54回高分子研究発表会(神戸)予稿集  2008.7 

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  • バイオイメージングを指向したシリコンナノ粒子の表面改質

    柴田靖久, 岩崎泰彦

    第54回高分子研究発表会(神戸)予稿集  2008.7 

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  • ホスホリルコリン基含有重縮合系および重付加系ポリマーの合成と性質

    堀口健二, 下山田直矢, 那川大輔, 長瀬裕, 岩崎泰彦, 石原一彦

    高分子学会  2008.5 

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  • ホスホリルコリン基含有ジアミンモノマーを用いたポリ(ウレタン-ウレア)の合成と性質

    2008.5 

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  • 新しい生分解性材料と用途開発

    岩崎泰彦

    第58回医用高分子研究会講演予稿集  2008 

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  • 生体に倣ったバイオマテリアルの創製

    岩崎泰彦

    第12回関西大学先端科学技術シンポジウム  2008 

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  • 抗体フラグメントを集積したポリマーブラシによる高感度分子認識界面の構築

    岩田綾子, 岩崎泰彦, 秋吉一成

    第56回高分子年次大会予稿集  2007 

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  • ポリリン酸エステルを基盤とした新規生分解性バイオマテリアルの創製

    岩崎泰彦, 榎本真司, 秋吉一成

    第29回日本バイオマテリアル学会大会講演予稿集  2007 

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    Event date: 2007

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  • 精密設計されたポリマーブラシ表面における生体分子の機能誘導

    岩田綾子, 岩崎泰彦, 秋吉一成

    第29回日本バイオマテリアル学会大会講演予稿集  2007 

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    Event date: 2007

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  • 細胞表層構造に倣った生体機能ポリマー界面の構築

    岩崎泰彦, 澤田晋一, 高見詩恵, 秋吉一成

    第56回高分子討論会予稿集  2007 

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    Event date: 2007

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  • ホスホリルコリン基含有芳香族ポリマーの合成と生体適合性

    堀口健二, 石原一彦, 岩崎泰彦, 長瀬 裕, 下山田直矢

    第56回高分子討論会予稿集  2007 

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    Event date: 2007

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  • ポリマーブラシを用いた高感度分子認識界面の創製-ブラシ構造と抗体集積化の関係

    岩田綾子, 秋吉一成, 岩崎泰彦

    第56回高分子討論会予稿集  2007 

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    Event date: 2007

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  • ペプチドを複合化したポリホスホエステルの調製と機能

    榎本真司, 秋吉一成, 岩崎泰彦

    第56回高分子討論会予稿集  2007 

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    Event date: 2007

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  • 生体に倣ったポリマーバイオマテリアルの設計

    岩崎泰彦

    第19回生体機能関連化学若手の会サマースクール  2007 

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    Event date: 2007

    依頼講演

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  • 標識糖鎖反応性ナノ粒子による細胞選択的薬物輸送

    岩崎泰彦, 真家春樹, 秋吉一成

    第56回高分子年次大会予稿集  2007 

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    Event date: 2007

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Industrial property rights

  • リビングラジカル重合開始基を持つポリリン酸の製造方法および用途

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    Patent/Registration no:特許第4727938号 

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  • ホスホリルコリン基を有する化合物、その重合体ならびにその製造方法

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    Patent/Registration no:特許第4628951号 

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  • ナノゲル工学によるハイブリッドゲルの調製とバイオマテリアル応用

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    Patent/Registration no:特許第4599550号 

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  • 二官能性有機リン化合物、重合体および製造方法

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    Patent/Registration no:特許第4441032号 

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  • 動物細胞固定化材及び動物細胞固定化法

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    Patent/Registration no:特許第4405769号 

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  • ポリホスフェート及びその製造方法並びに生分解性材料

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    Patent/Registration no:特許第4274827号 

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  • 血液適合性多孔質膜及びその製造方法

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    Patent/Registration no:特許第3808968号 

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  • 温度応答性を有するポリホスフェート化合物およびその製造方法

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    Patent/Registration no:特許第4781332号 

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  • 生分解性重合体の製造方法および用途

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    Patent/Registration no:特許第4727941号 

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  • 骨置換多孔質体形成用ペースト及びその製造方法

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    Application no:特願2011-027649 

    Patent/Registration no:特許5950498  Date registered:2016.7 

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  • ナノ粒子蛍光体の製造方法

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    Patent/Registration no:特許第5452098号 

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  • ホスホリルコリン基を有するジアミン化合物、その重合体ならびに製造方法

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    Patent/Registration no:特許第5276443号 

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  • 生体材料、及びそれを用いた人工関節並びにその製造方法

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    Patent/Registration no:特許第5100023号 

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  • 細胞固定化基材被覆膜用材料

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    Patent/Registration no:特許第5044777号 

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  • 化学センサ及びバイオセンサ

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    Patent/Registration no:特許第5011530号 

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  • 薬剤溶出性ステント

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    Patent/Registration no:特許第4967136号 

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  • 複合材料成形物及びその製造方法

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    Patent/Registration no:特許第4902162号 

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  • 末端官能性ホスホリルコリン類似基含有重合体、製造方法および用途

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    Patent/Registration no:特許第4824151号 

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  • 化合物連結糖タンパク質

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    Application no:特願2012-107821 

    Patent/Registration no:特許6153292  Date registered:2017.6 

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  • リン酸ジエステル−リン酸トリエステル共重合体およびその合成方法ならびに骨標的薬物輸送担体

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    Patent/Registration no:特許6679067B2  Date registered:2020.4 

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  • 細胞足場材料製造用組成物ならびに細胞足場材料およびその製造方法

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    Patent/Registration no:特許6840386  Date registered:2021.2 

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  • 化合物およびその合成方法ならびに重合体およびその合成方法

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    Patent/Registration no:特許7125751  Date registered:2022.8 

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Awards

  • Fellows of Biomaterials Science and Engineering

    2020.12  

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  • 日本バイオマテリアル学会賞(科学)

    2020.11   日本バイオマテリアル学会  

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  • 日本油化学会 オレオサイエンス賞

    2013.9   日本油化学会  

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    Country:Japan

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  • 日本バイオマテリアル学会科学奨励賞

    2009.11   日本バイオマテリアル学会  

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    Country:Japan

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  • 向科学技術振興財団創立10周年記念優秀賞

    2008.11   向科学技術振興財団  

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    Country:Japan

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  • 第54回高分子研究発表会(神戸)ヤングサイエンティスト講演賞

    2008.7   高分子研究発表会  

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    Country:Japan

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  • 日本人工臓器学会論文賞

    2006.11   日本人工臓器学会  

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    Country:Japan

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  • 高分子研究奨励賞

    2005.5   高分子研究奨励賞  

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    Country:Japan

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  • 日韓バイオマテリアル学会大会若手賞

    1999.9   日韓バイオマテリアル学会  

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Research Projects

  • Development of extracorporeal VAD housing having excellent blood compatibility using anti-fouling peptide immobilization technology

    Grant number:23KK0204  2023.9 - 2027.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Fund for the Promotion of Joint International Research (International Collaborative Research)

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    Grant amount:\20930000 ( Direct Cost: \16100000 、 Indirect Cost:\4830000 )

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  • Arbitrary arrangement of cells using photo-response of narrow-gap semiconductors

    Grant number:23H01715  2023.4 - 2026.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

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    Grant amount:\16770000 ( Direct Cost: \12900000 、 Indirect Cost:\3870000 )

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  • 転移性骨腫瘍の退縮と骨破壊を阻止する高分子医薬の開発

    Grant number:23H03750  2023.4 - 2026.3

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    岩崎 泰彦

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    Grant amount:\18460000 ( Direct Cost: \14200000 、 Indirect Cost:\4260000 )

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  • マクロファージを担体とした腫瘍標的薬剤輸送

    Grant number:21K19931  2021.7 - 2023.3

    日本学術振興会  科学研究費助成事業 挑戦的研究(萌芽)  挑戦的研究(萌芽)

    岩崎 泰彦

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    Grant amount:\6500000 ( Direct Cost: \5000000 、 Indirect Cost:\1500000 )

    本研究は,マクロファージを薬剤担体として利用し,腫瘍組織に対する高選択的な薬剤輸システムを構築することを目的として企画された.21年度はナノ粒子をマクロファージに固定化するための細胞表面の機能化とナノ粒子の調製について検討した。マクロファージの表面改質については従来から報告している糖代謝を利用した手法を採用しているが,細胞表面修飾による細胞への影響を最小にするために,新たなアミノ糖の合成を試みた.具体的には,脂溶性を高め,細胞への取り込み効率を著しく高めたものや,より温和な条件で化学修飾を可能にする官能基を担持させたN-アセチルマンノサミン誘導体の合成に成功した.新たに合成された誘導体はいずれも白色個体として得られ,NMR解析や質量分析により構造を確認した.新たに合成した類縁体は,これまで使用した垂涎体に比べ100~1000倍の効率で糖鎖改変できることも明らかにした.一方,ナノ粒子の調製については,細胞表面に誘導する非天然の官能基と自発的かつ生体直交的に反応するナノ粒子の作成を試みた.まず,原始移動ラジカル重合をはじめとるすリビングラジカル重合により,末端に官能基を導入した親水性ブロックと疎水性ブロックからなる種々のコポリマーを合成した.続いて,得られたコポリマーを分散安定剤として利用し, ナノ粒子の調製を行った.約100ナノメートルの粒径を有するナノ粒子を獲得することができ,また,調製したナノ粒子はコアに非水溶性の生分解性ポリマーを有するため,同粒子から脂溶性薬剤の徐放が可能になると考えている.

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  • Elucidation of mechanism and improvement of photo-response of cells on semiconductors; Development of multiple cells 3D printer

    Grant number:20H02467  2020.4 - 2023.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

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    Grant amount:\16640000 ( Direct Cost: \12800000 、 Indirect Cost:\3840000 )

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  • Dynamic regulation of cell behavior using stimuli-responsive polymers with dynamic crosslinks

    Grant number:20H04539  2020.4 - 2023.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

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    Grant amount:\17550000 ( Direct Cost: \13500000 、 Indirect Cost:\4050000 )

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  • Development of smart-bioactive materials beneficial for a paradigm shift in dental treatment

    Grant number:20H03871  2020.4 - 2023.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

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    Grant amount:\17940000 ( Direct Cost: \13800000 、 Indirect Cost:\4140000 )

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  • Investigation of optimal polyphosphoester structure for bone treatment

    Grant number:19H04474  2019.4 - 2022.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

    Iwasaki Yasuhiko

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    Grant amount:\16380000 ( Direct Cost: \12600000 、 Indirect Cost:\3780000 )

    Biodegradable polyphosphoesters (PPEs) are of increasing interest due to their promising biomedical applications. Polyphosphodiesters (PPDEs) have mineral affinity and therefore are promising polymer drug candidates for bone disease treatment. However, their effects on osteoblasts are still unclear. In this study, we investigated the effect of PPDEs on bone cell function and clarified that PPDEs upregulated osteoblastic differentiation whereas downregulated osteoclast differentiation. Furthermore, biodistribution of PPDEs in osteoporosis mouse model was studied. PPDEs selectively accumulated in bone tissue. Due to the molecular diversity of polyphosphoesters, various types of polymeric prodrugs for bone disease treatment can be designed based on PPDEs.

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  • Development of novel bone-affinity nanoparticles and its application to cancer bone metastasis-specific drug discovery

    Grant number:18K19656  2018.6 - 2021.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Challenging Research (Exploratory)  Challenging Research (Exploratory)

    Hiraga Toru

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    Grant type:Competitive

    Grant amount:\6370000 ( Direct Cost: \4900000 、 Indirect Cost:\1470000 )

    In the current study, we developed new nanoparticles that are expected to have high bone affinity and suppress uptake by reticuloendothelial cells, and investigated their effects on cancer bone metastasis. PMB-PEP nanoparticles were confirmed to have high bone affinity in vitro, but their ability to accumulate in bone tissue was not sufficient in vivo. Therefore, PMBA nanoparticles to which a bisphosphonate (alendronate) was added instead of PEP were prepared. High accumulation of PMBA nanoparticles in bone tissue was observed in vivo, and PMBA nanoparticles supplemented with an anticancer drug (docetaxel) significantly suppressed bone metastasis. These results suggest the possibility of applying PMBA nanoparticles to cancer bone metastasis-specific drug discovery.

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  • The effect of Poly (ethylene sodium phosphate) on bone strength and bone mineral density of femur in ovariectomized mice.

    Grant number:18K12045  2018.4 - 2021.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Yokota Atsushi

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    Grant type:Competitive

    Grant amount:\3380000 ( Direct Cost: \2600000 、 Indirect Cost:\780000 )

    To clarify the effect of newly-synthesized Poly (ethylene sodium phosphate), PEP・Na on bone strength and bone mineral density of femur, twelve-week-old ovariectomized (OVX) mice were administered multiple doses of PEP・Na (MPN group) every 4 weeks (total 3 doses). MPN mice were compared with OVX control mice (CTL group) by high-resolution peripheral quantitative computed tomography analyses at different time points to evaluate the BMD of the femur. In addition, biochemical examinations of the blood specimens were analyzed to assess the safety of PEP・Na administration. The increasing rate in BMD of MPN mice was significantly higher than that in the CTL group. Moreover, no adverse effects by PEP・Na administration were observed. These results indicate PEP・Na holds therapeutic potential for future application as treatment for osteoporosis.

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  • Cell surface engineering for cancer immunotherapy

    Grant number:17K20119  2017.6 - 2019.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Challenging Research (Exploratory)  Challenging Research (Exploratory)

    Iwasaki Yasuhiko, SUGUMOTO Shunsuke

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\6370000 ( Direct Cost: \4900000 、 Indirect Cost:\1470000 )

    Antigen-presenting cells play a dominant role in cancer immunotherapy. Tumor cells, however, can still resort to several mechanisms of immune evasion that ultimately lead to the development of tumor tissues. In the current study, we revealed that the surface modification of macrophages with nucleic acid aptamers improved the capture of tumor cells and enhanced their anticancer immune response. Regardless of the tumor cells condition (apoptotic or not), the number of tumor cells captured by surface modified macrophages was significantly higher than that captured by nontreated analogs. Phagocytosis of captured tumor cells, secretion of proinflammatory cytokines, and expression of MHC class molecules were accelerated in nucleic aptamer-modified macrophages when these were in contact with apoptotic tumor cells instead of living tumor cells.

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  • Preparation of multi-responsive nanocarrier by near infrared

    Grant number:17H03071  2017.4 - 2021.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

    遊佐 真一

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    Grant type:Competitive

    Grant amount:\17810000 ( Direct Cost: \13700000 、 Indirect Cost:\4110000 )

    We have prepared novel hydrophilic copolymers that can dissolve hydrophobic fullerenes in water. Fullerenes can efficiently convert near-infrared light energy into heat. The hydrophilic copolymers have a thermo-responsive unit. Although the thermo-responsive unit cannot dissolve in water at room temperature, it can dissolve in water at high temperature. Water-soluble complexes were formed with the copolymers and fullerenes. It was confirmed that the complex aqueous solutions generated heat upon irradiation of near-infrared light. Also active oxygen which kills the cancer cells can be generated from fullerenes in the complex upon light irradiation. Furthermore, it was confirmed that drugs such as anticancer drugs encapsulated into the complex at room temperature can be released from the complex upon heating.

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  • Development of a macromolecular prodrug for the treatment of bone

    Grant number:16H03185  2016.4 - 2019.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

    Iwasaki Yasuhiko, NOREE Susita, INOUE Naoyuki, HIRANO Yuya, KUNOMURA Shun

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\15990000 ( Direct Cost: \12300000 、 Indirect Cost:\3690000 )

    In the present study, we evaluated the effects of poly(ethylene sodium phosphate) (PEPNa), which is a kind of polyhpsphoesters (PPEs), on bone cell viability and activity. PEPNa exhibited excellent short-term biocompatibility with osteoblasts. In contrast, selective inhibition of osteoclast adhesion and function was observed following cultivation with PEPNa. Moreover, we have demonstrated that PEPNa shows good affinity for bone in vivo. Due to the molecular diversity of PPEs, various types of polymeric prodrugs for bone disease treatment can be designed based on PEPNa.

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  • Development of dual-function polymer with the ability to exhibit long-lasting antibacterial effects

    Grant number:16K15800  2016.4 - 2019.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research  Grant-in-Aid for Challenging Exploratory Research

    Imazato Satoshi

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    Grant type:Competitive

    Grant amount:\3510000 ( Direct Cost: \2700000 、 Indirect Cost:\810000 )

    In this study, five experimental surface coatings composed of copolymers of MDPB and MPC at different ratios were fabricated. Each coat was applied to the resin surface, and the protein repellent properties, antibacterial effects against Streptococcus mutans, and inhibitory effects of biofilm formation were evaluated. The copolymer composed of 15 (wt)% MDPB and 15(wt)% MPC inhibited protein adsorption and exhibited bactericidal effects on its surface, indicating that this composition was effective to achieve contact inhibition of bacteria in the presence of saliva.

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  • Development of hydrogels with the ability to release antimicrobials for long term and their application to various resin-based materials

    Grant number:26293409  2014.4 - 2017.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

    Imazato Satoshi

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    Grant type:Competitive

    Grant amount:\16380000 ( Direct Cost: \12600000 、 Indirect Cost:\3780000 )

    In this study, non-biodegradable hydrogels composed of HEMA and a cross-linking monomer TMPT, to be used as a reservoir of antimicrobials, were fabricated. These novel hydrogels were found to be able to work as a carrier of cetylpyridinium chloride (CPC), enabling long-term release of CPC in a wet environment. By incorporation of CPC-loaded polyHEMA/TMPT hydrogel particles, it is possible to provide MMA-based resins or HEMA-based endodontic sealers with long-lasting antibacterial effects, keeping their physical properties in clinically acceptable level.Thus, we successfully developed a sustained antimicrobial-release system useful for achievement of reconstructive materials which exhibit long-lasting antibacterial effects.

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  • 糖鎖改変技術を利用したバイオ輸送システム

    Grant number:26107719  2014.4 - 2016.3

    日本学術振興会  科学研究費助成事業 新学術領域研究(研究領域提案型)  新学術領域研究(研究領域提案型)

    岩崎 泰彦

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\6890000 ( Direct Cost: \5300000 、 Indirect Cost:\1590000 )

    本研究は細胞種に由来する特異性を活かした疾病治療を可能にするポリマーマテリアルの創出を目的として企画された。具体的には,研究期間において①糖鎖改変技術により免疫細胞の表面を核酸アプタマーを修飾し,この免疫細胞で特定の癌細胞を選択的に捕捉すること,②細胞膜の糖タンパク質を担持したナノマテリアルを調製し,これを医療展開するための要素技術を集積すること,について検討した。
    ①では,癌細胞の表面に過剰発現しているprotein tyrosine kinase 7 (PTK-7)に対して特異的に結合する核酸アプタマー(sgc8)を免疫細胞の表面に修飾した.糖鎖の生合成経路を介しマウスマクロファージ(RAW264.7)の表面にメタクリロイル基を誘導した.続いて,末端をチオール化したsgc8(sgc8-SH)と光ラジカル誘導剤(Eosin-Y)を添加し,可視光線を10分間照射した.
    RAW264.7の表面に修飾したsgc8をAlexa Fluor 488でラベル化された相補鎖を作用させることにより確認した.PTK-7を過剰発現しているヒト白血病細胞(CCRF-CEM)を穏やかに振盪しながら30分間接触させた.ネイティブの細胞やManM(-)の表面にはほとんどCCRF-CEM細胞が認められないのに対し,ManM(+)には多くのCCRF-CEM細胞が粘着していることが認められた.一部の粘着したCCRF-CEM細胞がRAW264.7細胞に貪食されることも認められた.
    ②では,白血球細胞由来の膜タンパク質P-セレクチン糖タンパク質リガンド-1(PSGL-1)と水溶性ポリマーの複合体を調製し,この複合体による活性化血管内皮細胞のターゲッティングを試みた。

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  • Application of thermo-sensitive complex containing photothermal conversion molecule, fullerene to cancer therapy

    Grant number:25288101  2013.4 - 2017.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

    Yusa Shin-ichi, YAMAGO Shigeru

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    Grant type:Competitive

    Grant amount:\18460000 ( Direct Cost: \14200000 、 Indirect Cost:\4260000 )

    We have developed a method to dissolve hydrophobic fullerene (C60) which shows photothermal conversion effect in water. Thermo-responsive diblock copolymers which were prepared via a controlled radical polymerization method were used to dissolve C60 in water by complex formation of the diblock copolymer with C60. The C60 complex was consisted of C60-containing core and thermo-responsive shells. The size of the C60 complex increased due to inter-complexes aggregation with increasing temperature. In the future when the C60 complex is injected into the body, the complex may accumulate at tumor site by warming around the affected part. If light is irradiated to the affected part, the temperature of C60 increased to damage tumor site.

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  • Formation of New Administrative Law in the Governance Space of Globalization and Public-Private Collabolation

    Grant number:25285008  2013.4 - 2016.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    Ichihashi Katsuya, KODAMA Shigeru, IWASAKI Yasuhiko, OBATA Kaoru, HAREYAMA Kazuho, HONDA Takio, TOKUDA Hiroto, SHIRAFUJI Hiroyuki, KUONG Teilee, YASUDA Rie

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    Grant amount:\15600000 ( Direct Cost: \12000000 、 Indirect Cost:\3600000 )

    The research team have been able to analyze the emergence of the new type of “Administrative Law” (administrative law in the form of avant la lettre) within the legal sphere created by the interactions between the public-private partnership schemes and the global legal phenomena. This legal sphere expands beyond the scope of the conventional administrative legal sphere, which has been characterized by two principal elements, namely (1) the law on administrative organizations and functions and (2) the nature of being a section of national law. These two elements are losing their distinctiveness in this new emerging legal sphere, where public-private partnership bodies, global and many diversified organizations emerge as actors; various normative rules have been created to subject these actors not only to national laws and regulations but also to some autonomous internal rules and treaties; the contractual relationship among these bodies and organizations has also been prevailed.

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  • Preparation of Smart Biomaterials Using Dynamic Crosslinks and Their Biomedical Applications

    Grant number:24300175  2012.4 - 2016.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

    Miyata Takashi, IWASAKI Yasuhiko

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    Grant type:Competitive

    Grant amount:\18200000 ( Direct Cost: \14000000 、 Indirect Cost:\4200000 )

    In this study, biomolecularly stimuli-responsive gels, particles and films with molecular complexes as dynamic crosslinks were strategically designed as smart biomaterials for constructing novel medical systems. The hydrogels, particles and films underwent changes in the volume in response to a target biomolecule. We developed self-regulated drug delivery systems (DDS) and diagnostic sensors using the biomolecularly stimuli-responsive gels, particles and films. In addition, photo-responsive polymers with micro-patternable surfaces were synthesized using photo-dimerization moieties as dynamic crosslinks. Photo-irradiation to the photo-responsive polymers through photo-masks resulted in the formation of micropatterns. The micropatterned surfaces were applied to microcontact printing and cell cultures.

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  • Preparation of polyphosphoesters for controlled bone remodeling

    Grant number:24500532  2012.4 - 2015.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    IWASAKI Yasuhiko

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\5330000 ( Direct Cost: \4100000 、 Indirect Cost:\1230000 )

    Polyphosphoesters are unique polymeric biomaterials because of their biocompatibility, biodegradability and bone affinity. Synthesis of poly(ethylene sodium phosphate) (PEP-Na) was achieved through ring-opening polymerization of 2-methoxy-2-oxo-1,3,2-dioxaphospholane followed by hydrolysis. We investigated the viability and function of human osteoclasts and murine osteoblasts precursors in contact with 100 mg/mL of PEP-Na This did not trigger any significant effect on osteoblast cell viability. In contrast, the polymer effectively reduced the adhesion of human osteoclasts on bone slices at concentration as low as 0.0001 mg/mL. Moreover, the in situ generation of resorption pits was also effectively reduced. This is the first report to demonstrate the possibility of using polyphosphoesters for selective inhibition of osteoclast function and bone resorption. This study indicates that PEP-Na has potential to be used as an effective polymer prodrug for bone therapy.

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  • 糖鎖改変技術を利用したセルベースデバイスの設計

    Grant number:24107524  2012.4 - 2014.3

    日本学術振興会  科学研究費助成事業 新学術領域研究(研究領域提案型)  新学術領域研究(研究領域提案型)

    岩崎 泰彦

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\7540000 ( Direct Cost: \5800000 、 Indirect Cost:\1740000 )

    細胞膜の表面にはあらゆる生体機能を司る糖鎖が存在している。糖鎖末端にはシアル酸(Neu5Ac)と呼ばれる糖残基が点在している。シアル酸の生合成は,ウリジン二リン酸(UDP)-N-アセチルグルコサミン(UDP–GlcNAc)から5段階の連続反応を経て合成される。はじめにUDP–GlcNAc がUDP-GlcNAc 2-エピメラーゼとN-アセチルマンノサミン(ManNAc)キナーゼによってManNAcを経てManNAc-6-Pに変換される。さらに,ManNAc-6-Pとピルビン酸の縮合により,Neu5Acが生成する。すなわち,Neu5AcはManNAcを前駆体として生合成される。
    我々は,この糖鎖改変技術をバイオマテリアル設計に利用することにより,細胞種に基づいた極めて特殊性に富むバイオマテリアルを創出できると考え,新たなManNAc 誘導体,N-メタクリロイルマンノサミン(ManMA)を合成した。ManMAを含む培地中で3日間培養された動物細胞の表面にメタクリロイル基が誘導されることを確認した。このメタクリロイル基を化学的に修飾し,生きた細胞への非天然機能の付与と生体膜画分を担持したポリマーマテリアルの合成を試みた。細胞膜糖鎖のシアル酸残基にメタクリロイル基を誘導し,これとチオール基をもつ温度応答性ポリマーを複合化した。温度刺激による細胞凝集の制御や糖タンパク質の回収に成功した。さらに,細胞由来の糖タンパク質を組み込んだポリマーゲルの調製も行った。

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  • Preparation of bone-specific polymer biomaterials

    Grant number:21680043  2009 - 2011

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (A)  Grant-in-Aid for Young Scientists (A)

    IWASAKI Yasuhiko

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\24830000 ( Direct Cost: \19100000 、 Indirect Cost:\5730000 )

    In order to prepare bone specific polymer biomaterials, we have synthesized polyphosphoester ionomers and compared their fundamental actions with bisphosphonates. The adsorption amount of polyphosphoester ionomers on hydroxy apatite(HAp) microparticles was increased with an increase in the ionized units in polyphosphoesters and the affinity of ionomers for HAp microparticles was enhanced by formation of sodium salt. Polyphosphoesters ionomers could significantly reduce HAp-formation compared with pamidronate. Moreover, the resorption of HAp was also reduced with addition of polyphosphoester ionomers as a similar to pamidronate. The cytotoxicity of polyphosphoester ionomers was significantly lower than that of pamidronate and cell compatibility of the ionomer further improved by sodium salt formation of the polyphosphoester ionomers. Furthermore, the increment in ALP activity and mineral deposition of mouse osteoblast cells in contact with ionomers was observed.

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  • Synthesis of Biomolecule-Responsive Gels and Construction of Intelligent Biomedical Systems

    Grant number:21300182  2009 - 2011

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

    MIYATA Takashi, IWASAKI Yasuhiko

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    Grant type:Competitive

    Grant amount:\18200000 ( Direct Cost: \14000000 、 Indirect Cost:\4200000 )

    In this study, biomolecule-responsive gels that underwent changes in the volume in response to a signal biomolecule were prepared as smart biomaterials for constructing novel bio-systems. Furthermore, self-regulated drug delivery systems(DDS), diagnostic sensors and so on were developed using biomolecule-responsive gels. We synthesized biomolecule-crosslinked gels and biomolecule-imprinted gels that swell and shrink in response to a signal biomolecule such as an antigen and a saccharide, and tried to apply their gels to DDS and diagnostic sensors.

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  • 脂質流動界面のアレイ化と分子認識

    Grant number:21106520  2009 - 2010

    日本学術振興会  科学研究費助成事業 新学術領域研究(研究領域提案型)  新学術領域研究(研究領域提案型)

    岩崎 泰彦

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\3770000 ( Direct Cost: \2900000 、 Indirect Cost:\870000 )

    生体膜は究極の生体機能界面を構築する自己組織体ととらえることができ、生体の化学的多様性を制御する役割を担っている。すなわち生体のあらゆる仕組みを解明するために、生体膜の働きを理解することは重要であり、これには脂質二分子膜を天然に近い状態で自在に調製する手法が不可欠である。しかし、現時点では脂質二分子膜を平面上に作成する方法は確立されていない。そこで、本研究は高分子濃厚ブラシを利用した新たな方法で脂質二分子膜をアレイ状に再構築し、流動性に富む表面環境を利用した分子認識界面を創出することを目的とし企画された。
    平成22年度は前年度に調製法を確立した脂質膜アレイ表面上での分子認識特性について評価した。リン脂質DOPCに所定量(数パーセント)の糖脂質(ガングリオシドGM1など)を混合し、直径50ナノメートル以下の一枚膜リポソームを調製した。これをパターン化濃厚ブラシ基板に接触させ脂質膜アレイを形成させた。糖脂質を複合化が膜の形態に及ぼす影響を蛍光顕微鏡観察で明らかにした。続いて複合化した糖脂質に対し特異的に作用する分子(アナライト)を接触させ、調製した脂質膜上で特異的ならびに定量的な結合が得られるか評価した。
    さらに、ゲル液晶転移温度の異なる脂質からなるリポソームを別々に調製し、これらのリポソームを混合して基盤に接触させることにより、生体膜を模倣したラフト構造を有する脂質吸着膜アレイを調製することに成功した。

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  • Well-defined design of biofunctional surfaces

    Grant number:18681018  2006 - 2008

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (A)  Grant-in-Aid for Young Scientists (A)

    IWASAKI Yasuhiko

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\19890000 ( Direct Cost: \15300000 、 Indirect Cost:\4590000 )

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  • Development of cellular adhesion control type dental implant coated by biocompatible polymer

    Grant number:18592112  2006 - 2007

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    TOMIZUKA Ken, OGASAWARA Toru, MORO Toru, IWASAKI Yasuhiko, ISHIHARA Kazuhiko

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    Grant type:Competitive

    Grant amount:\3500000 ( Direct Cost: \3200000 、 Indirect Cost:\300000 )

    It is clarified that MPC polymer, that has the phosphorus lipid polarity radical, coated to the surface of material control the cell and the protein adhesion. As a result, the biocompatibility and the blood compatibility of the device for the medical treatment can be rapidly improved. The possibility of the application of MPC Polymer to the dental implant body is examined aiming to control the cellular adhesiveness to the implant body, and to be longer-term and to make the implant function in vivo surely. The kind of MPC Polymer necessary to obstruct the cellular adhesion to the titanium plate surface first of all and the density was examined.
    First of all, the GFP tendency was made introducing the GFP gene by using the vector of the retrovirus for leaf system stem cell stock C3H10T1/2:] with stability and the appearing cell strain was made. As a result, it turned out PMB and PMS that the cellular adhesion was equally obstructed, and PMD was low the in hibition effect of the cellular adhesion. It was assumed that the plate of the same titanium alloy as the material of the implant body that had already been sold as aproduct was used because the appearance that the cell bonded was observed by the state etc. of grinding on the surface of the titanium plate, and however, Polymer adopted PMB and did a similar experiment. As a result, the effect of the cell bonding obstruction on the titanium alloy was admitted.

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  • Feasibility Study of Advanced Circulatory Support Devices that Enable Recovery and Optimal Therapy of Heart Failure in Pediatric and Adult Patients

    Grant number:18300149  2006 - 2007

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

    TAKATANI Setsuo, OHUCHI Katsuhiro, HOSHI Hideo, KATAOKA Hiroyuki, IWASAKI Yasuhiko, SHINSHI Tadahiko

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    Grant type:Competitive

    Grant amount:\17470000 ( Direct Cost: \15100000 、 Indirect Cost:\2370000 )

    This study addresses design and development of advanced circulatory support devices intended for short and intermediate duration of at least one month without requiring anti-coagulation therapy in children and adults, for allowing complete recovery, or for bridging to more advanced treatment modalities such as implantable devices or heart transplantation.
    To achieve the goal, for adult applications a disposable, magnetically levitated (Mag-lev) centrifugal blood pump having a prime volume of 23ml was designed by utilizing a compact magnetic bearing. The compact magnetic bearing was implemented by combining two-degree-of freedom active magnetic bearing in X- and Y- directions with permanent magnets passively restoring the position of impeller rotor in the axial and tilting axes. The rotation of impeller was attained through radial magnetic coupling between the inner driver magnet mounted on the motor shaft and the follower magnet molded inside the impeller-rotor. The pump performance analysis showed the maximum head pressure of 800mmHg against the pump flow of 5L/min at the rotational speed of 4500rpm. The hemolysis study revealed that the mechanical damage to blood cell elements was about the half that of the clinically used BioPump BPX-80. To date in vivo study using calves has shown that the pump system can meet requirements for one-week circulatory support in adult patients with minimum requirement of anti-coagulation therapy.
    As for pediatric application, a miniature centrifugal blood pump TinyPump having prime volume of 5ml and stable low flow control capability to 0.2L/min has been designed for 3-10Kg neonates and infants. The diameter of the impeller rotor is 30mm with six straight vanes resulting in the external diameter of the pump to be 50mm. The pump head is disposable, and easily attached and detached from the re-usable motor driver unit. The impeller rotor is rotated by radial magnetic coupling force between the 6 pole external drive magnets mounted on the motor shaft and the magnets molded inside the impeller-rotor. The impeller-rotor is supported by a hydrodynamic bearing at its center. The gap clearance of 150μm in the bearing of the impeller-rotor resulted in the secondary flow through the bearing area to be about 10% of the external flow. The application of the TinyPump for heart-lung bypass studies in 3Kg piglets revealed superior performance in comparison against the pediatric BioPump BP-50. The TinyPump was also used to support lung circulation in the single ventricle model to show stable pulmonary circulation. The TinyPump has also been used as a left ventricular assist device in the 3.5Kg swine and 10Kg Shiba-goats, demonstrating stable low flow, non-hemolytic and biocompatible support of circulation to the period up to two weeks. The study continues to demonstrate the stable and biocompatible performance in 10Kg Shiba-goats for the duration of 1-2 months.

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  • DETERMINATION OF MECHANISM FOR MOLECULAR ADHESION TO SOFT TISSUES AND MATERALS PREPARATION

    Grant number:17300144  2005 - 2007

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

    ISHIHARA Kazuhiko, IWASAKI Yasuhiko, KONNO Tomohiro

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    Grant type:Competitive

    Grant amount:\15590000 ( Direct Cost: \14600000 、 Indirect Cost:\990000 )

    In this study the polymer structures were determined to adhere the polymer to tissues. The molecular design of the polymers were carried out with attention to the regulation of cell/materials interactions from of the physical chemistry and the biological both sides. The polymers could easily solidify themselves by the phase transition of the polymers and voluntary organization as far the normal temperature and to realize the adhesion prescribed it. It prescribed the molecular structure of this polymers closely and composed it, and the wound produced the soft tissue adhesion materials of the prototype than adhesion performance and examination of the safety.
    A thought prepared nanoparticles as a probe for recognizing the specific reaction analytical technique that I found so far; and to prescribe the functional group, which could adhere for a cell, the structure of the ligand molecule. At first the functional groups with various hydrophobicity, electric charge, hydrogen bonding connected to use physicochemical interaction. The water-soluble phospholipid polymers, which did immobilization of the specific functional group was used for surface treatment materials and the polymer solution for making an O/W emulsion and manufactured nanoparticles.
    The functional groups cold introduce with high-density for suitable interaction with cells. The adhesion of cells and tissues could be achieved. To determine the structure and composition bonded this polymer to the cells, which became single-layered and examined the reply of the cell As well as a form, the number of the increases, the intracellular enzyme activity was measured to consider in particular cell activity It prescribed polymer composition, the chemical structure that did not affect a cell than these. On the other hand, a molecule design about the polymers was carries out to reduce adhesive property and performed examination form the viewpoint of prevention of organization adhesion.

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  • Design of hybrid hydrogels by nanogel engineering for biomaterials

    Grant number:17300147  2005 - 2006

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

    AKIYOSHI Kazunari, IWASAKI Yasuhiko, WATANABE Akihiko, MORIMOTO Nobuyuki

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    Grant type:Competitive

    Grant amount:\15000000 ( Direct Cost: \15000000 )

    Tailor-made functional nanogels and hydrogels were could created by self-assembly of functional associating polysaccharides. In particular, hydrophobized polysaccharides such as cholesterol-bearing pullulans formed physically cross-linked nanogels by their self-assembly in water. The nanogels can form complexes with proteins and nucleic acids. Macrogels with well-defined nanostructures can be obtained by self-assembly using these nanogels as building blocks. The self-assembling method using associating polymers is an efficient and versatile technique for preparing functional nanogels and hydrogels for application to bionanotechnology such as drug delivery system and artificial molecular chaperone. Nanogel-inorganic hybrid nanomaterials about nanogel-calcium phosphate and nanogel-Quantum dots were also described.

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  • 非天然膜糖鎖認識を介した新しい薬物輸送システムの開拓

    Grant number:17650132  2005 - 2006

    日本学術振興会  科学研究費助成事業 萌芽研究  萌芽研究

    岩崎 泰彦, 秋吉 一成, 森本 展行

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\3300000 ( Direct Cost: \3300000 )

    標識となる非天然糖鎖を細胞膜上に誘導する。N-レブリノマンノサミン(ManLev)を既報に従い合成した。モデル細胞としてヒト子宮頸癌細胞(HeLa細胞)を用いた。10%ウシ胎児血清を含む培地(Minimum Essetial Medium)に、最終濃度10mMになるようMaLeVを添加し、この培地中でHeLa細胞を3日間培養した。ManLevの細胞内代謝にともなう糖鎖へのケトン基の発現を、ヒドラジド基をもつ蛍光色素(Alexa Fluor 350 hydrazide)を用いて確認した。
    ManLevを処理してケトン基を誘導した細胞を新鮮な培地に移した後、ヒドラジド基を表面にもつリン脂質ポリマーナノ微粒子を添加した。ナノ粒子の内部に予め蛍光物質(Nile Red)を内包させることにより、蛍光顕微鏡(現有設備)で、粒子の集積具合を追跡した。ヒドラジド基を持つ粒子は非天然糖鎖を誘導した細胞に集積することが認められたが、ヒドラジド基を持たないナノ粒子もしくは非天然糖鎖を誘導しなかった細胞ではナノ粒子の細胞集積は認められなかった。トルイジンブル一法による細胞毒性試験では、ナノ粒子自身の細胞毒性は認められなかった。一方、ナノ粒子の内部に代表的な脂溶性抗ガン剤を封入し、細胞に接触させたところ、細胞集積が起こった条件で効果的に細胞毒性が発現された。以上の結果から、細胞膜糖鎖と選択的に反応するナノ粒子により標的の細胞を効果的に攻撃できる新たなマテリアルとシステムを伴に構築することができた。

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  • 分子シャペロン機能を有するナノゲルキャリアによる新規DDSの開発

    Grant number:17012008  2005

    日本学術振興会  科学研究費助成事業 特定領域研究  特定領域研究

    秋吉 一成, 松田 修, 岩崎 泰彦, 渡辺 昭彦, 森本 展行, 野村 慎一郎

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    Grant type:Competitive

    Grant amount:\9000000 ( Direct Cost: \9000000 )

    本研究では、これまでの知見をもとに、独自に開発した分子シャペロン機能を有する自己組織化ナノゲル複合体を用いて、癌治療における新しいDDSの設計とその応用を目的とする。悪性腫瘍に対する治療の一つとして、各種の免疫療法が従来より試みられている。このような治療においてインターロイキン12(IL-12)は、高い抗腫瘍効果を持つサイトカインの一つとして注目されている。しかしながら、サイトカインを用いた免疫療法においては、その短い半減期に示される生体内での不安定性や、大量・反復投与による副作用などが、有効な抗腫瘍効果を得るための障壁となっているのも事実である。そこで我々は、IL-12の生体内投与時における安定性を向上する目的で、コレステロール基を修飾したプルラン(CHP)よりなるヒドロゲルナノ粒子(ナノゲル)(30nm)のキャリアとしての機能に着目した。マウスrecombinant IL-12とCHPとを種々の条件下で混合し、IL-12・ナノゲル複合体微粒子を調製した。その後ELISA法にてIL-12の活性を計測し、ナノゲルとの複合化条件を検討した。調製したIL-12・ナノゲル複合体微粒子の機能を評価するために、マウスの脾臓より採取したCD4陽性T細胞をin vitroで刺激し、産生されるIFN-γをELISAで経時的に測定した。さらにin vivoでの作用を以下の実験で検討した。Balb/cマウス由来の肉腫細胞、CSA1M細胞を同系マウスの皮下に接種し、皮下腫瘍モデルマウスを作成した。これにIL-12・ナノゲル複合体微粒子を投与し、腫瘍体積の変化を計測した。
    得られた結果より、IL-12はCHPナノゲルと相互作用して効率よく複合体微粒子を形成し、その後ナノゲルから生理活性を失うことなく放出できるシャペロン機能を発揮することが確認できた。またin vivo実験において、IL-12・ナノゲル複合体微粒子を6日間隔で3回という非常に少ない投与により、腫瘍の有意な増殖抑制が得られた。ナノゲル担体が優れた徐放機能を有していることがわかった。さらに、徐放性の優れた架橋ナノゲル(100-200nm)の調整法も確立した。本法は、サイトカイン免疫療法の欠点を克服するための新しいテクノロジーを切り開く可能性があると考えられる。

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  • Role of orexin in the regulation of sleep-wakefulness in rats

    Grant number:16614003  2004 - 2005

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    HONDA Kazuki, IWASAKI Yasuhiko, KATAYAMA Yoshifumi, HIRAI Keiji

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    Grant type:Competitive

    Grant amount:\3800000 ( Direct Cost: \3800000 )

    Orexins A and B are novel neuropeptides which are known to be regulated in the control of feeding and arousal state. Recent studies showed that canine narcolepsy is caused by a deficit in the orexin 2 receptor (OX2R) gene, and that prepro-orexin knockout mice exhibited similar behavior to human and canine narcoleptics. Orexin-containing neurons are localized in the lateral hypothalamic area and densely project to the monoaminergic locus coeruleus, dopaminergic ventral tegmental area, serotonergic dorsal raphe nuclei and histaminergic tuberomammillary nucleus. An intracerebroventricular (ICV) infusion of orexin A and orexin B induced significant arousal effects in freely behaving rats. Hence, brain vigilance state seems to be regulated by the orexin network systems. Orexin A co-administration with pyrilamine significantly inhibited the effects of orexin A-induced wakefulness. Since direct synaptic connectivity from orexin nerve terminals to histaminergic neurons in the tuberomammillary nucleus (TMN) where the OX_2R is abundantly expressed, we investigated the effects of intraperitoneal (ip) injection of alpha-fluoromethylhistidine (FMH), a histamine synthesis inhibitor, on orexin-induced wakefulness in rats. Pretreatment with alpha-FMH, significantly inhibited the orexin B-induced wakefulness in rats. This study therefore suggests that arousal state regulation by orexin neurons is mediated through the histaminergic system in the TMN. Furthermore, we have determined the arousal effects of newly developed selective orexin receptor type 2 agonist, [Ala^<11>]orexin-B, on the sleep-wake cycle in rats. The effects of ICV infusion of [Ala^<11>]orexin-B (1,10 and 40 nmol) during the light period dose-dependently resulted in a significant increase in wake duration and a significant decrease in rapid eye movement (REM) and non-REM sleep. The efficacy of [Ala^<11>]orexin-B was comparable to that of native peptides at the same dose. These findings suggest that orexin receptor type 2 plays an important role in the modulation of sleep-wake state and behavioral responses.

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  • 抗カンジダ付着性アクリルレジンの開発

    Grant number:16659528  2004 - 2005

    日本学術振興会  科学研究費助成事業 萌芽研究  萌芽研究

    向山 仁, 岩崎 泰彦, 堀内 三吉, 谷口 尚

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    Grant type:Competitive

    Grant amount:\3300000 ( Direct Cost: \3300000 )

    デンチャープラーク中に認められるC.albicansは義歯の材料であるpoly(methyl methacrylate)(以下PMMA)と強く付着する。義歯表面上のC.albicansの付着を防止することは患者及び歯科医にとって重要な課題である。2-methacryloyloxyethl phosphorylcholine polymer(以下MPCポリマー)はさまざまな医療器具表面に使用されている。MPCポリマーでコートされたPMMA上でC.albicansの付着抑制が推測されることから、コートされたPMMA表面においてC.albicansの付着を評価した。MPC共重合体(以下PMB)はMPCポリマーとn-ブチルメタクリレート(以下BMA)で合成されたものを使用した。MPCポリマー30mol%含有のPMB30と80mol%含有のPMB80を用意した。それぞれのPMBの濃度を0.5wt%に調整し、コート材とした。PMMA円盤(以下PMMAディスク)を用意した。PMB30溶液でコートされた60枚のPMMAディスクを準備しC.albicans菌液200μlと液体培地2mlを混入し培養した。これら60枚のうち30枚のPMMAディスクは、グラム染色した。残りの30枚のPMMAディスクは洗浄後、グラム染色した。各PMMAディスク表面を光学顕微鏡像のデジタル写真撮影を行い画像解析ソフトにてPMMAディスクに付着したC.albicansの面積の割合を評価した。PMB80においてもPMB30と同じ方法で評価した。さらにコートされていないPMMAディスクを対照群とし、同様の方法で評価した。統計学的分析は、1元配置分散分析(ANOVA)およびScheffe's testを用いて有意水準5%で行った。洗浄ならびにコートをともに行わなかったPMMAディスクは他のPMMAディスクとのすべての組み合わせにおいて有意差が認められた。そして、洗浄しコートを行わなかったPMMAディスクと洗浄を行い、PMB30あるいはPMB80でコートしたPMMAディスクの間に有意差が認められた。

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  • 生体内環境に想起された生分解性ヒドロゲルの創製と生理活性タンパク質の放出制御

    Grant number:15700324  2003 - 2004

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    岩崎 泰彦

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\3200000 ( Direct Cost: \3200000 )

    前年度に合成法を確立したヒドロゲルの物性、生体適合性の評価ならびにタンパク質の放出特性について調べた。
    ホスフェート結合を有する高分子架橋剤(PIOP)と2-メタクリロイルオキシエチルホスホリルコリン(MPC)をラジカル共重合することにより含水可能なゲルを得ることができた。このゲルの含水率はPIOPの組成が高くなるにつれ低下した。また、PIOPの組成によりゲルの機械的強度も変化した。ヒドロゲルの非酵素的加水分解速度は塩基性(pH11.0)環境下で大きく、酸性(pH4.0)および中性(pH7.4)では小さくなった。非酵素的加水分解は主鎖のポリホスフェートが分解して起こることが、^1H-NMR等から明らかとなり、分解生成物には低分子量リン酸化合物および、poly(MPC)が含まれることがわかった。これらの分解生成物をマウス繊維芽細胞の培養系に添加しても細胞毒性は、認められなかった。また、ラット皮下にヒドロゲルを埋入し周辺組織の炎症反応を調べたところ、ヒドロゲル周辺の皮下組織は正常状態と同様であり、ゲルとの接触に伴う反応は認められなかった。
    凍結乾燥したゲルをトリプシンの溶解している緩衝溶液に浸し、膨潤させた。ゲルを簡易洗浄した後、緩衝溶液に浸し、ゲルから溶離したトリプシンの定量と活性評価を行った。ゲルより放出されたトリプシンの活性は、ネイティブのものと変化なく、ゲルとの接触に伴う活性の低下は認められなかった。また、ゲル内に取り込まれたトリプシンは一日でほぼ全量放出された。タンパク質の放出時間を制御するためにポリホスフェートの疎水性を変化させたゲルの作成も検討している。
    以上の結果から重合性基をもつポリホスフェートで架橋したMPCヒドロゲルは生体適合性にも優れており、今後医学や薬学で利用可能な新しいヒドロゲルとして期待できる。

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  • Design of bio-nanosystem by dynamic control of nanoorganization

    Grant number:15300158  2003 - 2004

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

    AKIYOSHI Kazunari, IWASAKI Yasuhiko, WATANABE Akihiko, MORIMOTO Nabuyuki

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    Grant type:Competitive

    Grant amount:\17000000 ( Direct Cost: \17000000 )

    The research could create novel bio-nanosystem with the function of artificial molecular chaperone for biotechnology and medicine by dynamic control of nanogel particles. In particular, 1.Nanogels, composed of cholesterol bearing pullulan (CUP), -cyclodextrin (CD) systems have been used in order to assist with protein refolding as a novel molecular chaperone-inspired system. The CHP nanogels selectively trapped non-native proteins and CD acted as an effector molecule to control the binding ability of the host to proteins. It indicated the possibility to design various functional nanogels and to apply for refolding chromatography and batchwise renaturation. 2.Dynamic CHP-CD nanogels were characterized by SEC and SEC-MALS methods. The nanogels prevented the thermal aggregation of protein by selective trapping of the heat-denatured protein. After the complex between the CHP-CD nanogels and protein was cooled, the enzyme activity of protein spontaneously recovered upon release from the complex. The dynamic nanogels self-regulated an association of heat denatured protein and dissociation of native protein depending on the concentration of CD. The thermal stability of CAB was improved by thermoresponsive controlled association between the proteins and the artificial molecular chaperone. This is a novel example of a thermoresponsive controlled association between a protein and an artificial chaperone. CHP-CD nanogel systems are useful as protein stabilized reagents. 3.Novel photoresponsive nanogels were prepared by the self-assembly of spiropyrane-bearing pullulan (SpP). The solution properties of the nanogels could be controlled by photostimulation via isomerization between hydrophobic spiropyrane and hydrophilic merocyanine. The molecular chaperone-like activity of the nanogels in protein refolding was investigated. The activity of citrate synthase significantly increased when the amphiphilicity of SpP nanogels was switched by photostimulation.

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  • Basic Researches on the Micropositioning techniques of Cells and Biomaterials for Tissue Engineering

    Grant number:14380393  2002 - 2004

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

    NAKAMURA Makoto, TAKATANI Setsuo, OHUCHI Katsuhiro, IWASAKI Yasuhiko, MORITA Ikuo, HORIE Mikio

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    Grant type:Competitive

    Grant amount:\17300000 ( Direct Cost: \17300000 )

    Biological tissues and organs are constructed with a microscopic structure, with several types of cells and extra cellular matrixes, in three dimensionally. Therefore, it is very important in the field of tissue engineering to establish the technologies to position living cells and biological materials precisely onto an intentionally targeted position.
    In this research project, we have been aiming to make basic researches and to produce some innovative technologies to position living cells onto the targeted position, to contribute to develop tissue engineering. As some of the promising approaches, we have investigated the feasibility of micropositioning techniques of living cells and biomaterials such as using inkjet printing and micromanipulation techniques. And we summarized the concept and discussed about the possibilities of these approaches for tissue engineering.
    We focused mainly on the inkjet techniques for tissue engineering. We have challenged to eject living cells using inkjet machine, and have investigated the damages of the ejected cells. As a result, we have recognized that we could eject living cells without significant damages. To avoid drying of cells and to construct three-dimensional structures, we developed a gel formation technique by inkjet printing. With this technique, we could prevent cells from drying and succeeded in the construction of three dimensional gel structures such as a lattice and a tube with fine gel fibers, including living cells in them. Such techniques for micropositioning of cells and biomaterials enables us to manufacture biological tissues with the techniques of computer aided designing and manufacturing. Innovative tissue engineering will come true.
    Then, we designed a microvasculature pattern and evaluated it using the technique of computational fluid dynamics. In addition, we constructed computational three-dimensional model of organs from a clinical CT scan data, and made some three dimensional cast models based on such CAD data using three-dimensional printer.
    In these ways, we have made basic researches on the micropositioning techniques of cells and biomaterials for tissue engineering and have demonstrated the possibility of these approaches using computer and micropositioning techniogies. Collaboration of advanced computer and mechanical technologies with tissue engineering will surely contribute to the future of tissue engineering medicine.

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  • Comprehensive Basic Research for Development of Advanced, Innovative Permanent Artificial Heart Systems

    Grant number:14208103  2002 - 2004

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)  Grant-in-Aid for Scientific Research (A)

    TAKATANI Setsuo, SAKAMOTO Tohru, ARAI Hirokuni, SHINSHI Tadahiko, SHIMOKOHBE Akira, IWASAKI Yasuhiko

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    Grant type:Competitive

    Grant amount:\52520000 ( Direct Cost: \40400000 、 Indirect Cost:\12120000 )

    In this research, basic research covering following items was conducted ;
    1.In the pulsatile artificial heart that is based on the electromechanical principle, the durability of the roller screw mechanism was improved by coating the friction surface with a diamond-like-carbon coating. The ventricular assist device continued to operate for duration of 13 months in the 37 degree C bath. The failure in the ball bearing that supports the roller screw movement caused termination of the study.
    2.Magnetic levitation (MagLev) mechanism was investigated to achieve a mechanical contact-free centrifugal blood pump. A two-degree-freedom MagLev system was developed to attain a disposable extracorporeal blood pump and an implantable system. The power requirement in the MagLev system was reduced to less than 1.0watt with controllability being less than 20 micron meter. The hemolytic performance of the MagLev centrifugal blood pump was improved by a factor of 6-7 in comparison to the clinical standard BPX-80.
    3.The computational fluid dynamics (CFD) analysis was conducted to evaluate the mechanical design of the MagLev centrifugal blood pump designed in section 2. Flow visualization was also carried out to verify the numerical predictions to optimize the pump design.
    4.Basic research was also extended to evaluate the deformation and recovery response of red blood cells under cyclically reversing shear flow. A specially built shear flow generator was used to simulate a condition similar to that inside the centrifugal blood pumps. The results of the study can be used to improve the blood pump design.
    5.The optical reflectance sensor utilizing the fiber-optics was developed to detect thrombus formation inside the cardiovascular devices. Its application in oxygenators and blood pumps will be investigated.
    6.A surgical navigation system was developed to assist implantation of the artificial heart system. The CT images and CAD data of the device were used to construct the proper implantation scheme of the device in patients prior to surgery. The prototype was tested in calf for VAD implantation.

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  • Studies on the role of histaminergic system in orexin-induced wakefulness in rats.

    Grant number:14570912  2002 - 2003

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    HONDA Kazuki, IWASAKI Yasuhiko

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    Grant type:Competitive

    Grant amount:\3500000 ( Direct Cost: \3500000 )

    Orexins A and B are novel neuropeptides involved in the regulation of feeding and arousal state. Orexin-containing neurons are localized in the lateral hypothalamic area and densely project to the locus coeruleus, ventral tegmental area, dorsal raphe nuclei and tuberomammillary nucleus (TMN). Previously, we reported that intracerebroventricular (icy) infusion into the third ventricle of both orexins A and B induced arousal effect in the rats. Recently, we found direct synaptic connectivity between orexin nerve terminals and histaminergic neurons in the TMN where the OX2R is abundantly expressed. Hence, orexin-induced arousal state seems to be regulated via histaminergic neurons in the TMN. In this study, we investigate the effects of icy infusion of pyrilamine (an Hi receptor antagonist) on orexin-induced wakefulness in rats. Cortical FEG and neck EMG were monitored for three consecutive days, during continuous icy saline infusion at a rate of 10 rd/h. For diurnal period, orexin A (1 nmol/20 ul saline) and pyrilamine (25 or 75 ug/25 ul saline) replaced the icy infusion of saline. Pyrilamine administration was started 30 mm before orexin A infusion. The icy infusion of orexin A for a 2-h period markedly increased the amount of wakefulness by 340.0 % (p<0.05) over the baseline value. Pyrilamine decreased orexin A-induced wakefulness by 85 % (p<0.05) and 58 % (p<0.05), at 25 and 75 ug/2.5-h period, respectively. Pyrilamine caused a dose-dependent decrease in the orexin A-induced arousal effect. Orexin A-induced suppression of non-REM sleep was dose-dependently reversed by pyrilamine treatment. Although pyrilamine treatment alone (75 ug) slightly decreased REM sleep, no significant difference was observed. Pyrilamine, an Hi receptor antagonist, significantly inhibited the effects of orexin A-induced wakefulness. Since orexin neurons densely innervate TMN where OX_2R is highly expressed, orexin neurons might regulate the arousal state through modulating the activity of histaminergic neurons in the TMN.

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  • シャペロニング機能を有する分子シンクロシステムの構築

    Grant number:13022233  2002

    日本学術振興会  科学研究費助成事業 特定領域研究  特定領域研究

    秋吉 一成, 森本 展行, 渡辺 昭彦, 岩崎 泰彦

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    Grant type:Competitive

    Grant amount:\3600000 ( Direct Cost: \3600000 )

    本研究では、タンパク質の状態とシンクロして分子シャペロニング機能を発現しえる新規な動的機能性ナノゲルの設計と利用を図っている。スピロピランは、フォトクロミズムに伴って親水性・疎水性の変換や大きな構造変化を引き起こす化合物である。従来の疎水基に変えて高分子の会合制御因子として、この分子を多糖に部分置換した新規会合成高分子スピロピラン置換プルラン(SpP)の合成とその会合挙動を検討してきた。その結果、SpPはナノ微粒子を形成し、光、熱により動的に会合状態が変化する新しいナノ微粒子であることが明らかになった。本年度は、このナノ微粒子の蛋白質のリフォールディングにおけるシャペロン作用について検討し、新しい光応答性人工分子シャペロンとして機能することが明らかになった。SpPナノ微粒子のシャペロン作用を、モデル酵素としてホモ2量体であるCitrate Synthase(CS、Mw_<subunit>=50,000)を用いて検討を行った。CS(1.0mg/ml)を6MGuHClによって変性させ、50倍希釈によるリフォールディング実験を行った。希釈後の酵素活性を測定し、天然状態のそれと比較することで活性回復率を見積もり、シャペロン活性を評価した。自発的な系では30%しか酵素は再生しなかった。一方スピロ型(Spiro)のSpPナノ微粒子を調製し、可視光照射下リフォールディング実験を行ったところわずかながらシャペロン活性が見られた(〜40%)。メロシアニン型(Mer)のSpPナノ微粒子を調製し暗所下においてリフォールディングを行わせると、顕著なシャペロン活性を示した(〜60%)。さらに、Merでリフォールディングを開始し暗所下で30分ほど放置してから、可視光照射しSpiroにした系では、非常に大きなシャペロン活性を示した(80%)。このようにSpPはスピロピラン基の親水性・疎水性を制御することで高いシャペロン作用を示す新しいシステムとして機能することが明らかになった。

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  • Structure Control and Functions of Biocompatible Polymer Alloy as Biomaterials

    Grant number:13480288  2001 - 2004

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

    ISHIHARA Kazuhiko, WATANABE Junji, IWASAKI Yasuhiko

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    Grant type:Competitive

    Grant amount:\14700000 ( Direct Cost: \14700000 )

    In this research, polymer alloys composed of conventional polymer materials, such as, polyurethane and polysulfone, polyolefine and newly designed phospholipid polymers were researched as follows :
    To improve the biocompatibility of a segmented polyurethane (SPU), 2-methacryloyloxyethyl phosphorylcholine (MPC) copolymer was blended in the SPUs, such as Pellethane【○!R】 and TM-3【○!R】, by a solvent evaporation method from a homogeneous solution containing both SPU and MPC copolymer. X-ray electron spectra(XPS) indicated that the MPC moieties were located at the surface of the SPU membrane blended with the MPC copolymer even when the composition of the MPC copolymer was only 7.5 w/w % against the matrix SPU. The mechanical property of the SPU membranes, as determined by tensile stress-strain measurements, changed very little by addition of the MPC copolymer. Biocompatibility of the MPC copolymer blended membrane was evaluated by plasma protein adsorption and blood cell adhesion on the surface. The amount of fibrinogen adsorbed on the SPU membrane significantly decreased by addition of the MPC copolymers. Moreover, addition of MPC copolymer in the SPU membrane suppressed platelet adhesion and activation. It is concluded that the blending of the MPC copolymer in the SPU membrane is an effective method to improve biocompatibility of the SPU membrane.
    Nonfouling polysulfone hollow fiber membranes from protein adsorption and deposition were newly developed by addition of MPC polymer. To improve hydrophilicity, permeability, and nonfouling characteristics of the PSf hollow fiber in a hemodialyzer, we synthesized a MPC polymer, which can be blended with PSf for preparing the polymer alloy (PSf/MPC polymer). The composition of the MPC polymer blended in the PSf was in the range between 7.0 and 15-wt%. From the PSf/MPC polymer solution, flat membranes and hollow fiber could be prepared. These membranes took an asymmetric structure and its mechanical strength was good. The surface characterization of the PSf/MPC polymer hollow fiber membrane by XPS revealed that the MPC units were concentrated at the surface. The permeability for solutes through the PSf/MPC polymer membrane was higher and the amount of protein adsorbed on the PSf/MPC polymer membrane was lower than those of the PSf membrane. Moreover, platelet adhesion was also effectively inhibited on the PSf/MPC polymer membrane

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  • Developing and clinical application of a highly reliable dentin-bonding system.

    Grant number:12470404  2000 - 2002

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

    WATANABE Akihiko, MORIMOTO Nobuyuki, IWASAKI Yasuhiko, AKIYOSHI Kazunari

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    Grant type:Competitive

    Grant amount:\5800000 ( Direct Cost: \5800000 )

    After mechanical preparation of the tooth cavity with rotating instrument, the smear layer is formed on the dentin surface. Owing to the disturbance of resin adhesion to dentin, smear layer is always removedby an echant, The strong bonding to dentin can be achieved by the diffusion of resin molecules to the resulting demineralized dentin. Under some circumstances, the demineralized dentin was left surround the cavity wall after resin polymerization. The remaining demineralized dentin would be hydrolyzed and impairs the dentin bond durability greatly. For reducing the amount of residual demineralized dentin, the integrity of collagen structure should be preserved as possible. In addition, the thickness of demineralized dentin should be reduced as possible. Therefore, the milder echant should be used to leave more hydroxyapatite in the hybrid layer. The resin content in the hybrid layer is also important. It is suggested that the bond durability is attributed to the property of dentin substrate. However, few studies have reported on the effect of dentin substrate condition on bond durability. It is well accepted that the diffused resin could be polymerized and hybridized in the demineralized dentin layer. In this study, a reliable light-curing dentin bonding agent was established according to this concept. In wet bonding technique, the diffusion ability of resin to demineralized dentin can be increased by repeated priming procedure. The resin content was increased in the hybrid layer. A high quality adhesive layer was established. EDTA is known to remove the smear layer and demineralized the underneath sound dentin (thickness : 1μm〜2μm). Monomer in this layer is polymerized and hybridized with dentin. A blue laser with the wave-length of 473 nm, can be used to cure the resin monomer in the demineralized dentin layer. A reliable curing system for curing commercial dentin bonding agents was established.

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  • Preparation of non-biofouling blood bags

    Grant number:12558103  2000 - 2001

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

    IWASAKI Yasuhiko, ISHIHARA Kazuhiko, MORIMOTO Nobuyuki, WATANABE Akihiko

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\11400000 ( Direct Cost: \11400000 )

    The surface of polyethylene (PE) was modified by grafting with various water-soluble polymers to control blood/materials interactions. This study was carried out in order to improve our understanding of the effect of chemical structure of water-soluble polymers grafted on the PE surface on platelet function when the platelets were in contacted the surface, Water-soluble polymers, such as poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), poly(acrylamide) (PAAm), poly(N-vinylpyrrolidone) (PVPy), and poly[monomethacryloyl poly(ethylene glycol)] (PMPEG) were grafted on low-density PE sheets by photoinduced graft polymerization. PE bags modified with water-soluble polymers and non-modified PE bags were prepared by heat processing.
    The activation of platelets after storage in the PE bags was evaluated by measuring the cytoplasmic free calcium ion concentration ([Ca^<2+>]i). The [Ca^<2+>]i of platelets in contact with the PE surface grafted with PMPC was the same level as that of native platelets and significantly less than that in contact with other PE surfaces grafted with water-soluble polymers. The number of adherent platelets was effectively decreased on PE surfaces grafted with PMPC and PMPEG compared with non-treated PE. The aggregation ability of platelets was also measured after storage of platelet-rich plasma in the PE bags. The PE surface grafted with PMPC demonstrated a significantly decrease in aggregation ability compared with the non-treated PE, and that grafted with PAAm, PVPy, and PMPEG. We conclude that surface modification with PMPC is the most effective among these water-soluble polymers in preserving platelet functions.

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  • Artificial Enamel : Preparation and Evaluation.

    Grant number:11470403  1999 - 2000

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B).  Grant-in-Aid for Scientific Research (B).

    NAKABAYASHI Nobuo, WATANABE Akihiko, IWASAKI Yasuhiko

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    Grant type:Competitive

    Grant amount:\6200000 ( Direct Cost: \6200000 )

    Preparation of hybridized dentin is a key to make bonding of resin to dentin possible. The purpose of this study was to compare efficacy of dissolved various valent cations in 10% phosphoric acid on wet bonding to dentin. It was hypothesized that addition of multivalent cation in etchant could improve the monomer permeability of wet demineralized dentin that would make the bond strength higher. Bovine dentin prepared with 600-grid paper was etched with 10% phosphoric acid dissolved 22.0mM sodium chloride (Na), calcium chloride (Ca) or ferric chloride (Fe) for 10s. The specimens were rinsed and blot-dried. They were primed with 5% 4-META in acetone for 60 s three times. And then a MMA-TBB resin was applied. Mini-dumbbell test specimens were trimmed from the bonded samples.
    Through a study of bonding to dentin it was realized that demineralized dentin not protected by interpenetration resin can easily be affected by hydrolysis, which we call secondary caries. Once enamel is removed, dentin is exposed to the outside and is vulnerable to caries, and pulp is also exposed to the outside through tubles in the exposed dentin. Then microorganisms invade the pulp easily ; this we call hypersensitive dentin. Microleakage and secondary caries have been very important problems to be solved in dentistry. When we can provide an impermeable membrane like enamel on the exposed dentin, it must be very effective to protect dentin from cariesand pulp from invasion of microorganisms.

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  • 生分解性リン脂質ポリマーの合成と機能評価

    Grant number:11878175  1999 - 2000

    日本学術振興会  科学研究費助成事業 萌芽的研究  萌芽的研究

    中林 宣男, 岩崎 泰彦

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    Grant type:Competitive

    Grant amount:\2100000 ( Direct Cost: \2100000 )

    本研究では、生体に優しい生分解性リン脂質ポリマー(新規化合物)の合成法を確立し、化学的な構造・機能解析を行うと伴に医学、薬学への応用を検討することを目的としている。現在、バイオマテリアルの分野で最もポピュラーな生分解性ポリマーがポリ乳酸やポリグリコール酸などの脂肪族ポリエステルである。脂肪族ポリエステルは一見、生体に無害の様に思われるが、分解生成物の残存や分解速度、さらに生体適合性の点でその安全性が問われている。
    申請者らは生体膜類似構造に着目して分子設計したリン脂質ポリマーが優れた生体適合性を示すこと明らかにしてきた。そこで、リン脂質極性基を有する生分解性ポリマーを合成する考えに至った。
    平成11年度に引続き代表的なリン脂質極性基であるホスホリルコリン基を有する脂肪族ポリカーボネート(PPC)の合成の検討を行った。本研究で新規に合成した1、3-ジクロロイソプロピルホスホリルコリン(DCPC)と1,4-ジブロモブタンを所定濃度で混合し炭酸カリウムとクラウンエーテルを加えアセトニトリル中で重合しPPCを得た。PPCの構造はNMRおよびFT-IRで解析し、PPC中のリン脂質ユニット組成はリンの定量より求めた。PPCの分子量測定はゲル浸透クロマトグラフィー(GPC)を用いて行った。これらの結果より分子量約10000程度のPPCを合成できた。本研究で合成したPPCはいずれも水溶性でありDCPCユニットを30モル%有するPPCは水溶液中の濃度が5x10^<-3>を越えると会合することが明らかとなった。
    リン脂質極性基を有するポリカーボーネートに加え、脂肪族ポリエステルについても検討を行っている。

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  • 新規な細胞/組織工学用材料の創製と機能評価

    Grant number:11780615  1999 - 2000

    日本学術振興会  科学研究費助成事業 奨励研究(A)  奨励研究(A)

    岩崎 泰彦

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\2200000 ( Direct Cost: \2200000 )

    本研究では、生体との非特異的な相互作用が小さいリン脂質ポリマーを用いて、特定の細胞を安定に保持できる新しい組織/細胞工学用材料の創製を目的としている。
    平成11年度はリン脂質ポリマーの化学構造,表面組成および修飾方法の違いによる細胞挙動への影響を個々の細胞で評価し、MAPCポリマーのみでの細胞機能制御の可能性を検討した。本年度は、生理活性物質をリン脂質ポリマー表面に固定化し、生体成分との作用を評価した。2-メタクリロイルオキシエチルホスホリルコリン(MPC)と2-エチルへキシルメタクリレート(EHMA)と2-アミノエチルメタクリレート(AEMA)の三元共重合体を合成し、サイトカイン(IL-2)およびヘパリンを化学結合ならびにイオン結合でそれぞれ固定化した。白血球の活性および血液凝固について評価したところ、IL-2を固定化した表面では白血球のIL-2レセプターへのシグナル伝達機序から予測できる活性化が認められた。IL-2の活性に与える結合部位(アミノ基・アルデヒド基)の表面組成の影響も認められ、適度な濃度を選ぶことによりIL-2の活性が効果的に得られることが明らかとなった。一方、ヘパリンを固定化した表面では、MPCユニットのタンパク質非吸着・血液細胞非粘着特性とヘパリンの抗凝固活性の相乗効果が認められ天然の血管内皮膜を啓もうした、新しい血液適合性表面を構築することができた.さらに現在、接着系細胞の成長因子を固定化した表面においても検討を行っている。
    MPCポリマーの生体適合性をRT-PCR法を用いて評価したところ、典型的な培養基質に接着した細胞に比べ、MPCポリマー表面に接着した細胞はサイトカインのmRNAの産生量が有意に少なく細胞におよぼす刺激が弱いことも明らかにした。

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  • PREPARATION OF NOVEL HEMOCOMPATIBLE HOLLOW FIBER MEMBRANE AND DEVICE FOR SAFETY BLOOD PURIFICATION HOME

    Grant number:10558131  1998 - 2001

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

    ISHIHARA Kazuhiko, IWASAKI Yasuhiko

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    Grant type:Competitive

    Grant amount:\6700000 ( Direct Cost: \6700000 )

    Blood compatible hollow fibers were prepared from a polymer alloy composed of polysulfone(PSf) and 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer. To improve hydorophilicity, non-fouling characteristics, and blood compatibility of the PSf hollow fiber in a hemodialyzer, we synthesized a MPC polymer which can be blended with PSf for preparing the polymer alloy (PSf/MPC polymer). The content of the MPC polymer blended in the PSf was 7 and 15 wt%. The PSf/MPC polymer hollow fiber could be prepared by both wet and dry-wet processing methods. The hollow fiber took an asymmetric structure and its mechanical strength was enough for practical use for hemodialysis. The surface characterization of the PSf/MPC polymer hollow fiber by X-ray photoelectron spectroscopy revealed that the MPC unit were concentrated PSf/MPC polymer hollow fiber was higher and the amount of protein absorbed on the PSf/MPC polymer hollow fiber was lower than those of the PSf hollow fiber Moreover, platelet adhesion was also effectively inhibited on the PSf/MPC polymer hollow fiber. Based on these results, the addition of the MPC polymer to the PSf is a very useful method to improve the functions and blood compatibility of the hollow fiber . From the PSf/MPC polymer hollow fibers, the mini-module for hemodialysis was prepared . Preliminary animal experiments demonstrated that it had excellent antithrombogenic property and permeability for solute during the experiment even when any anticoagulant PSf/MPC polymer is provided to the medical device production company in Japan and new blood purification device is under developing.

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  • 細胞機能を傾斜的に制御するリン脂質ポリマーの合成

    Grant number:10123208  1998

    日本学術振興会  科学研究費助成事業 特定領域研究(A)  特定領域研究(A)

    岩崎 泰彦, 石原 一彦

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\1400000 ( Direct Cost: \1400000 )

    生体膜を構成する主要成分であるリン脂質と同様な極性基を有するω-メタクリロイルオキシアルキルホスホリルコリン(MAPC)ポリマーがタンパク質の吸着および細胞の粘着を抑制し,優れた血液適合性を示すことをこれまでに明らかにした.本研究では,MAPCの化学構造の違いが生体適合性に与える影響を明確にするためにpoly(MAPC)の密度を傾斜的に変化させた表面を作製した.この表面と生体成分との相互作用をpoly(MAPC)の化学構造・密度・運動性・配向性に着目して評価した.無可塑性のPEシートにエネルギを変化させながらコロナを照射し,傾斜的に活性な表面を作製した.コロナ照射エネルギーが増すに連れてPE表面に生成した逼酸化物の量は増加した.このPEシートをMAPCのエタノール溶液に浸潰し60℃でも時間重合した.Poly(MAPC)のグラフト小密度は過酸化物の生成量すなわちコロナ照射エネルギーが増すに連れて増し,poly(MAPC)の傾斜表面を作製することができた.ヒト血漿より吸着したフィブリノーゲンの量はpoly(MAPC)のグラフト密虜が増すに連れて減少した.この傾向は他のタンパク質においても確認され,poly(MAPC)で修飾することにより非特異的にタンパク質の吸着を抑制することが明らかとなった.MAPCユニットのメチレン鎖長で比較すると,主鎖と極性基間の繰り返し単位が6のpoly[6-メタクリロイルオキシヘキシルホスホリルコリン(MHPC)]が最もタンパク質の吸着を抑制した.蛍光プローブを用いた評価から,poly(MHPC)の配向性が他のpoly(MAPC)に比べ有意に高く,このことがタンパク質の吸着抑制に寄与していることが示唆された.血小板および繊維芽細胞の粘着性もpoly(MHPC)をグラフトした表面が最も効果的に低かった.傾斜表面により,Poly(MAPC)の表面密度および化学構造の違いによるタンパク質吸着性および細胞粘着粘着性が変化することを明確にすることができた.

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  • PREPARATION OF NOVEL BIOMEDICAL POLYMERS HAUING BIOMEMBRANE-LIKE SURFACE AND RECOGNITION OF THEIR NON THROMBOGENIC

    Grant number:09480250  1997 - 2000

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B).  Grant-in-Aid for Scientific Research (B).

    ISHIHARA Kazuhiko, IWASAKI Yasuhiko

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    Grant type:Competitive

    Grant amount:\8500000 ( Direct Cost: \8500000 )

    Novel polymer biomaterials, which can use in contact with blood, are prepared with strong inspiration from the surface structure of biomembrane. That is, the polymers with phospholipid polar group in the side chain, 2-methacrylooyloxyethyl phosphorylcholine (MPC) polymers were synthesized. The MPC polymers can inhibit surface-induced clot formation effectively, even when they contact with blood in the absence of anticoagulant. This phenomenon was due to reduction of plasma protein and suppression of denaturation of adsorbed proteins. That is, the MPC polymers interact with blood components very mildly.
    The amount of protein adsorbed on the polymer surface had a close relation to the free water fraction in the hydrated polymer. A comparison of the conformational change in proteins adsorbed on the MPC polymers and poly (HEMA) revealed that the effectiveness of the phosphorylcholine group in preventing the change, and the protein on the MPC polymer maintained its original state. Thus, it is concluded that the free water fraction is one of the most important factors in controlling the protein adsorption process.
    As the molecular structure of the MPC polymer was easily designed by changing monomer units and composition, it could apply to surface modification of artificial organs and biomedical devices for improving blood compatibility and tissue compatibility. Thus, the MPC polymers are useful polymer biomaterials for making high performance artificial organs and biomedical devices to provide safety medical treatments.

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  • Long-durable bonding of resin to dentin

    Grant number:09557151  1997 - 1999

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

    NAKABAYASHI Nobuo, WATANABE Akihiko, IWASAKI Yasuhiko, ISHIHARA Kazuhiko

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    Grant type:Competitive

    Grant amount:\7700000 ( Direct Cost: \7700000 )

    Bonding of 4-methacryloyloxyethyl trimellitate anhydride in methyl methacrylate initiated by tri-n-butyl borane in the presence of poly(methyl methacrylate) (4-META/MMA-TBB resin) to dentin via hybridizatin of impregnated monomers that polymerize in situ was first described by Nakabayashi et al. in 1982. This concept was accepted in worldwide and many bonding systems were developed since then.
    Longevity of bonding is essential for dental treatments. Many dental people do not understand that demineralized dentin accepts hydrolysis in mouth event it is mainly composed of collagen. Complete hybridization is keen to provide long-durable bond to dentin but it has been difficult to eliminate the demineralized dentin. Monomer permeability of demineralized dentin is as important as diffusibility of monomers to dissolve this problem. The effects of etchants and/or primers on wet-bonding to dentin were examined. The morphological change of demineralized dentin after contact with chemicals was observed by atomic force microscope. The pretreatment of tooth substrate to obtain durable bonding to dentin was proposed in this research. We also advise that the bonding test using mini-dumbbell specimens is essential to identify defects in bonded specimens, which are impossible by conventional test specimens.

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  • Excellent biocompatibility of MPC polymers as biomaterials evaluated by fibroblast and HL-60 cells.

    Grant number:09680847  1997 - 1999

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    WATANABE Akihiko, ISHIHARA Kazuhiko, IWASAKI Yasuhiko, NAKABAYASHI Nobuo, SUZUKI Yoshiaki

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    Grant type:Competitive

    Grant amount:\2900000 ( Direct Cost: \2900000 )

    Attachment of cells to a biomaterial surface are initiated the protein adsorbed there. When protein adsorption are prevented, cellular attachment must be minimized. Copolymers of methacryloyloxyethyl phosphorylcholine (MPC) have affinity for phospholipids due to the phosphorylcholine polar groups on surface. It has been found that they are useful biomaterials for blood contacting devices as they do not induce platelet activation and blood coagulation.
    We realized that MPC surfaces inhibited attachment oh HL-60 cells and moreover they did not promote cytokine production. This result suggested that the MPC surface did not stimulate the cells. On the other hand conventional biomaterials promote accumulation of cytokine in the cells. We could conclude that MPC is very excellent biomaterials which do not give adverse effect on the cells. Further, this evaluation method must be applicable to examine biocompatibility of biomaterials. Another interesting result was fibroblast cell could not attack on the surface coated with MPC copolymers. On the other hand, when the coating was removed by Ne ion injection, they could attach and prolify there. Protein adsorption here was confirmed also.

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  • 血液適合性材料としてのリン脂質ポリマーの合成及び機能評価

    Grant number:09780795  1997 - 1998

    日本学術振興会  科学研究費助成事業 奨励研究(A)  奨励研究(A)

    岩崎 泰彦

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\2000000 ( Direct Cost: \2000000 )

    本研究は、血管内皮表面類似構造を材料表面に構築することのできる新規なリン脂質ポリマーを合成及び、血液適合性の評価を目的としている。
    抗血栓性を材料に付与する新たな考え方として血管内皮表面の構造に着目し、これを材料表面に構築することの有効性が認められている。リン脂質極性基を有するメタクリル酸エステルポリマー(MPCポリマー)は、血液と接触した際に、表面にリン脂質を優先的に吸着し、組織化構造を形成するために優れた血液適合性を示す。
    この考え方を一歩進めて、より安定なリン脂質吸着層を形成させるための表面を、リン脂質ユニットの構造及び組成、既存の医用高分子への修飾法を詳細に検討することにより実現した。平成9年度において合成したリン脂質ポリマーを用いてポリマー表面に構築されたリン脂質自己組織化表面の解析と血液適合性の評価を行った.リン脂質分子の吸着量及びその吸脱着挙動は水晶発振子マイクロバランス法(QCM法)および原子間力顕微鏡(AFM)を用いて解析した結果,安定なリン脂質分子の組織化構造をポリマー材料表面で構築することを見出した。
    リン脂質ポリマーを被覆した架橋PMMAビーズを所定量チューブに充填しカラムを作成し、ミクロスフィアカラム法にてポリマーと血液との相互作用を評価した。リン脂質組織化吸着表面を構築する表面は,血漿タンパク質の吸着および血小板の粘着・活性化を効果的に抑制することが明らかとなり,血液適合性ポリマーを創製する上で極めて有効な概念になることを確信した.

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  • リン脂質ポリマーによる生体分子の自己組織化誘起と新規な医用材料としての機能評価

    Grant number:09217211  1997

    日本学術振興会  科学研究費助成事業 重点領域研究  重点領域研究

    石原 一彦, 岩崎 泰彦

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    Grant type:Competitive

    Grant amount:\1500000 ( Direct Cost: \1500000 )

    本研究は,血漿中に存在するリン脂質分子のポリマー表面への吸着を促進し,自己組織化した表面を構築するという概念を実現する新規なポリマーを合成し,これを新しい医療デバイスに応用するための学術的知見を集積することを目的とした.すなわちリン脂質分子に対して強い親和性を示すポリマーを用いると,リン脂質分子が優先的に吸着し,濃縮されるため,自己組織化特性により極性基を水相側に高度に配向させた組織化表面を形成すると考えた.まず,リン脂質に対して高い親和性を持たせるために側鎖にホスホリルコリン基を有するモノマー(MPC)を一成分として有するポリマーを合成した.さらに,重合性基とリン脂質極性基の間のメチレン鎖長(スペーサー部分)を変化させたMPC類縁体(MAPC)を合成し,MPCと同様に疎水性モノマー(n-ブチルメタクリレート(BMA))との共重合反応を行った.これらポリマーのリン脂質分子との親和性についていくつかの分子相互作用の要素に分けて解析した.さらに表面に形成されるリン脂質吸着層の組織化構造について確認するとともに,安定な組織化表面を創るためのポリマー分子の構造を規定した.形成された組織化表面と血液との相互作用を細胞及びタンパク質の階層ごとに分けて解析し,血液適合性発現に重要な因子を探索した.タンパク質の吸着量が少なく,吸着したタンパク質の二次構造変化も既存のポリマーに比較して小さいことがわかった。血小板粘着及び接触しただけの血小板の粘着について活性化の程度を測定したところ,MAPCポリマー上での活性化の抑制効果が認められた.MAPC表面をリポソームで前処理すると,MAPC組成が少ないポリマーにおいても効果的に血液適合性が発現することが見いだされた.これは生体膜類似表面の有効性を示している.

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  • Effect of Miniaturized Dumbbell-Shaped Specimen to Identify Bonding of Bovine Dentin

    Grant number:08457503  1996 - 1998

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

    NAKABAYASHI Nobuo, IWASAKI Yasuhiko, WATANABE Akihko, ISHIHARA Kazuhiko

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    Grant type:Competitive

    Grant amount:\6000000 ( Direct Cost: \6000000 )

    A reliable method for bonding resin to dentin was proposed. The procedure described hybridization of dentin substrates by impregnation and polymerization of adhesive monomers therein, creating a 'hybridized dentin' or 'hybrid layer. Often, applied adhesive monomers do not fully penetrate the acid-conditioned substrate, and a zone of demineralized dentin that is not resin-impregnated is left sandwiched between the hybridized dentin and the unaltered underlying mineralized dentin. An unfilled zone of the demineralized dentin causes defects in bonded dentin. It was very difficult to examine the presence of the defect at the base of the hybrid layer was not understood when the amount of [strength of unfilled zone] x [the area] was larger than the resin or bond strength. Thus, the results of conventional tensile bond strength measurement have often been misinterpreted. The defects in the bonded dentin were investigated by soaking the specimens in water to decrease the strength of collagen by the hydrolysis. However, it takes a long time to ascertain whether the dentin bond is excellent or not. These results persuaded us to develop a method to measure tensile bond strength on specimens which have the same cross-section at the bonded area. Dumbbell-shaped dentin bonded specimens must be a good candidate as dumbbell specimens are generally used to measure tensile strength of materials.
    It was reported that the defects in bonded bovine dentin were formed when the dentin was treated with an aqueous solution of 10% citric acid/3% ferric chloride for 10 sec. The defects were observed in using dumbbell specimens, but not in conversional specimens.
    It was also clear that defective dentin bond is not so good even when cohesive failure in resin was observed by the conventional test. When adhesive monomers more fully impregnated the entire region of demineralized dentin, the quality of the dentin bond was excellent. We will continue to develop such bonding systems to provide stable adhesion without defects by using dumbbell specimens.

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  • リン脂質分子を自己組織化吸着させる高分子の合成と血液適合性材料としての機能評価

    Grant number:08231215  1996

    日本学術振興会  科学研究費助成事業 重点領域研究  重点領域研究

    石原 一彦, 岩崎 泰彦

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    Grant type:Competitive

    Grant amount:\1500000 ( Direct Cost: \1500000 )

    生体膜の主要構成成分であるリン脂質と同じ極性基を有する2-メタクリロイルオキシエチルホスリルコリン(MPC)ポリマーは、天然のリン脂質に対し強い親和性を有し、血液と接触した際に優先的にリン脂質を表面に吸着する。吸着したリン脂質分子がMPCユニットと協同的に自己組織化して生体膜類似構造を形成するため極めて優れた血液適合性を示す。本研究ではモデルリン脂質として、ジパルミトイルホスファチジルコリン(DPPC)を用い、DPPCリポソームのリン脂質ポリマー表面への吸着状態解析することと組織化構造体構造の確認を目的とした。MPC及びその類縁体とn-ブチルメタクリレート(BMA)とのポリマーを効率よく合成することができた。このリン脂質ポリマーと比較材料としてポリ(2-ヒドロキシエチルメタクリレート)(PHEMA)を用いた。リポソーム溶液を添加後、MPCポリマー表面では極めて短時間に平衡吸着に達していた。一方、PHEMAで断続的な低下がみられた.すなわちMPC共重合体表面には吸着しているのに対し、PHEMAにはリポソームが重合体内部に拡散しているものと考えられた。リポソームで処理したポリマー表面を原子間力顕微鏡で観察すると、PHEMAでは吸着したリポソームの扁平化が認められた。一方,リン脂質ポリマー(PMEB30)では,リポソームの球状の形態が維持されていることがわかった。これよりMPCポリマーはリポソームの構造を安定化させる効果も有すると結論できた。

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Devising educational methods

  • 講義内容に沿った簡易実験の実施 授業評価の実施 国際学会および論文発表の奨励 専門分野を基軸とした国際交流の奨励

Teaching materials

  • 教科書:「バイオマテリアルの基礎」日本医学館、共著

Teaching method presentations

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Special notes on other educational activities

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