Researcher Database

Takayuki Nonoyama
Faculty of Advanced Life Science
Associate Professor

Researcher Profile and Settings

Affiliation

  • Faculty of Advanced Life Science

Job Title

  • Associate Professor

Degree

  • Doctor of Engineering(2013/03 Nagoya Institute of Technology)

URL

Research funding number

  • 50709251

ORCID ID

J-Global ID

Research Interests

  • Glass Transition   Phase Separation   Soft ceramics   Metal nanoparticle   Self-assembled monolayer   Organic/Inorganic hybrid materials   Bone bonding   Hydroxyapatite   Polypeptide   Bioceramics   Hydrogel   Biomineralization   

Research Areas

  • Nanotechnology/Materials / Polymer materials
  • Nanotechnology/Materials / Inorganic materials
  • Natural sciences / Bio-, chemical, and soft-matter physics
  • Nanotechnology/Materials / Structural and functional materials
  • Nanotechnology/Materials / Composite materials and interfaces

Educational Organization

Academic & Professional Experience

  • 2021/06 - Today Hokkaido University Faculty of Advanced Life Science Associate Professor
  • 2020/04 - 2021/05 Hokkaido University Faculty of Advanced Life Science Special-Appointment Associate Professor
  • 2020/04 - 2021/03 Hokkaido University Global Station for Soft Matter, Global Institution for Collaborative Research and Education (GSS, GI-CoRE) Special-Appointment Associate Professor
  • 2017/01 - 2021/03 Center for Innovation and Business Promotion, Hokkaido University Department of High Toughness Hydrogels for Cartilage Application
  • 2016/04 - 2020/03 Global Station for Soft Matter, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University Special-Appointment Assistant Professor
  • 2013/04 - 2020/03 Hokkaido University Faculty of Advanced Life Science Special-Appointment Assistant Professor

Education

  • 2010/04 - 2013/03  Nagoya Institute of Technology  Graduate School of Engineering  Department of Frontier Materials

Association Memberships

  • THE CHEMICAL SOCIETY OF JAPAN   THE CERAMIC SOCIETY OF JAPAN   THE SOCIETY OF POLYMER SCIENCE, JAPAN   

Research Activities

Published Papers

  • Ryuji Kiyama, Yong Zheng, Takayuki Nonoyama, Jian Ping Gong
    Soft Matter 19 (40) 7724 - 7730 1744-683X 2023/09 [Refereed][Not invited]
     
    The first fractographic mirror radius analysis for soft hydrogel materials was conducted. The universal −1 power law between fracture stress and mirror radius was established, in contrast to the different power law of linear elastic hard materials.
  • Satoshi Tanikawa, Yuki Ebisu, Tomáš Sedlačík, Shingo Semba, Takayuki Nonoyama, Takayuki Kurokawa, Akira Hirota, Taiga Takahashi, Kazushi Yamaguchi, Masamichi Imajo, Hinako Kato, Takuya Nishimura, Zen-ichi Tanei, Masumi Tsuda, Tomomi Nemoto, Jian Ping Gong, Shinya Tanaka
    Scientific Reports 13 (1) 2023/02/14 [Refereed]
     
    Abstract Neural regeneration is extremely difficult to achieve. In traumatic brain injuries, the loss of brain parenchyma volume hinders neural regeneration. In this study, neuronal tissue engineering was performed by using electrically charged hydrogels composed of cationic and anionic monomers in a 1:1 ratio (C1A1 hydrogel), which served as an effective scaffold for the attachment of neural stem cells (NSCs). In the 3D environment of porous C1A1 hydrogels engineered by the cryogelation technique, NSCs differentiated into neuroglial cells. The C1A1 porous hydrogel was implanted into brain defects in a mouse traumatic damage model. The VEGF-immersed C1A1 porous hydrogel promoted host-derived vascular network formation together with the infiltration of macrophages/microglia and astrocytes into the gel. Furthermore, the stepwise transplantation of GFP-labeled NSCs supported differentiation towards glial and neuronal cells. Therefore, this two-step method for neural regeneration may become a new approach for therapeutic brain tissue reconstruction after brain damage in the future.
  • Naohiro Kashimura, Yuki Suzuki, Takayuki Nonoyama, Jian Ping Gong
    Chemistry of Materials 0897-4756 2023 [Refereed][Not invited]
     
    Learning from nature is a promising approach to achieving specific functions of synthetic materials. The high material functions, in turn, shed light on the fundamental mechanisms underlying the high performance of biological tissues. For instance, bone is an attractive metabolic tissue with fascinating capabilities from the perspective of both biochemical and biomechanical functionalities. Bone tissue exhibits exceptional mechanical performance as a skeleton, enabling to sustain the locomotion of mammals. In this study, we design coupled reactions for self-regulatory sacrificial bond formation in poly(acrylic acid) hydrogels by introducing biomineral hydroxyapatite (HAp) found in bones. We demonstrate that through five coupled reactions, HAp regulates the Ca2+ bridging to the acidic polymer and toughens the hydrogels in water by the sacrificial bonds effect. This work is expected not only to greatly contribute to the design of tough soft materials but also to give deep insights into the self-regulated bone-toughening mechanisms.
  • Ryo Morita, Takayuki Nonoyama, Daisuke Abo, Takeshi Soyama, Noriyuki Fujima, Tetsuaki Imai, Hiroyuki Hamaguchi, Takuto Kameda, Osamu Sugita, Bunya Takahashi, Naoya Kinota, Kohsuke Kudo
    Journal of Vascular and Interventional Radiology 1051-0443 2023/01 [Refereed]
  • Akira Hirota, Jean-Emmanuel Clément, Satoshi Tanikawa, Takayuki Nonoyama, Tamiki Komatsuzaki, Jian Ping Gong, Shinya Tanaka, Masamichi Imajo
    Cancers MDPI AG 14 (23) 5890 - 5890 2022/11/29 [Refereed][Not invited]
     
    Retinoic acid (RA) and its synthetic derivatives, retinoids, have been established as promising anticancer agents based on their ability to regulate cell proliferation and survival. Clinical trials, however, have revealed that cancer cells often acquire resistance to retinoid therapy. Therefore, elucidation of underlying mechanisms of retinoid resistance has been considered key to developing more effective use of retinoids in cancer treatment. In this study, we show that constitutive activation of ERK MAP kinase signaling, which is often caused by oncogenic mutations in RAS or RAF genes, suppresses RA receptor (RAR) signaling in breast cancer cells. We show that activation of the ERK pathway suppresses, whereas its inhibition promotes, RA-induced transcriptional activation of RAR and the resultant upregulation of RAR-target genes in breast cancer cells. Importantly, ERK inhibition potentiates the tumor-suppressive activity of RA in breast cancer cells. Moreover, we also reveal that suppression of RAR signaling and activation of ERK signaling are associated with poor prognoses in breast cancer patients and represent hallmarks of specific subtypes of breast cancers, such as basal-like, HER2-enriched and luminal B. These results indicate that ERK-dependent suppression of RAR activity underlies retinoid resistance and is associated with cancer subtypes and patient prognosis in breast cancers.
  • Ryuji Kiyama, Masahiro Yoshida, Takayuki Nonoyama, Tomáš Sedlačík, Hiroshi Jinnai, Takayuki Kurokawa, Tasuku Nakajima, Jian Ping Gong
    Advanced Materials 35 (1) 2208902 - 2208902 0935-9648 2022/11/09 [Refereed]
     
    In this work, the authors succeed in direct visualization of the network structure of synthetic hydrogels with transmission electron microscopy (TEM) by developing a novel staining and network fixation method. Such a direct visualization is not carried out because sample preparation and obtaining sufficient contrast are challenging for these soft materials. TEM images reveal robust heterogeneous network architectures at mesh size scale and defects at micro-scale. TEM images also reveal the presence of abundant dangling chains on the surface of the hydrogel network. The real space structural information provides a comprehensive perspective that links bulk properties with a nanoscale network structure, including fracture, adhesion, sliding friction, and lubrication. The presented method has the potential to advance the field.
  • Mu, Q., Cui, K., Wang, Z.J., Matsuda, T., Cui, W., Kato, H., Namiki, S., Yamazaki, T., Frauenlob, M., Nonoyama, T., Tsuda, M., Tanaka, S., Nakajima, T., Gong, J.P.
    Nature Communications 13 (1) 2041-1723 2022/10/20 [Refereed]
     
    Abstract Living organisms share the ability to grow various microstructures on their surface to achieve functions. Here we present a force stamp method to grow microstructures on the surface of hydrogels based on a force-triggered polymerisation mechanism of double-network hydrogels. This method allows fast spatial modulation of the morphology and chemistry of the hydrogel surface within seconds for on-demand functions. We demonstrate the oriented growth of cells and directional transportation of water droplets on the engineered hydrogel surfaces. This force-triggered method to chemically engineer the hydrogel surfaces provides a new tool in addition to the conventional methods using light or heat, and will promote the wide application of hydrogels in various fields.
  • Zhiping Jin, Hailong Fan, Toshiya Osanai, Takayuki Nonoyama, Takayuki Kurokawa, Hideki Hyodoh, Kotaro Matoba, Akiko Takeuchi, Jian Ping Gong, Miki Fujimura
    Proceedings of the National Academy of Sciences of the United States of America 119 (42) e2206685119  2022/10/18 [Refereed]
     
    Liquid embolic agents are widely used for the endovascular embolization of vascular conditions. However, embolization based on phase transition is limited by the adhesion of the microcatheter to the embolic agent, use of an organic solvent, unintentional catheter retention, and other complications. By mimicking thrombus formation, a water-soluble polymer that rapidly glues blood into a gel without triggering coagulation was developed. The polymer, which consists of cationic and aromatic residues with adjacent sequences, shows electrostatic adhesion with negatively charged blood substances in a physiological environment, while common polycations cannot. Aqueous polymer solutions are injectable through clinical microcatheters and needles. The formed blood gel neither adhered to the catheter nor blocked the port. Postoperative computed tomography imaging showed that the polymer can block the rat femoral artery in vivo and remain at the injection site without nontarget embolization. This study provides an alternative for the development of waterborne embolic agents.
  • Nonoyama, T.
    Journal of the Ceramic Society of Japan 130 (10) 817 - 824 1348-6535 2022/10/01 [Refereed][Invited]
  • Ryo Nakamichi, Shang Ma, Takayuki Nonoyama, Tomoki Chiba, Ryota Kurimoto, Hiroki Ohzono, Merissa Olmer, Chisa Shukunami, Noriyuki Fuku, Guan Wang, Errol Morrison, Yannis P Pitsiladis, Toshifumi Ozaki, Darryl D'Lima, Martin Lotz, Ardem Patapoutian, Hiroshi Asahara
    Science translational medicine 14 (647) eabj5557  2022/06 [Refereed]
     
    How mechanical stress affects physical performance via tendons is not fully understood. Piezo1 is a mechanosensitive ion channel, and E756del PIEZO1 was recently found as a gain-of-function variant that is common in individuals of African descent. We generated tendon-specific knock-in mice using R2482H Piezo1, a mouse gain-of-function variant, and found that they had higher jumping abilities and faster running speeds than wild-type or muscle-specific knock-in mice. These phenotypes were associated with enhanced tendon anabolism via an increase in tendon-specific transcription factors, Mohawk and Scleraxis, but there was no evidence of changes in muscle. Biomechanical analysis showed that the tendons of R2482H Piezo1 mice were more compliant and stored more elastic energy, consistent with the enhancement of jumping ability. These phenotypes were replicated in mice with tendon-specific R2482H Piezo1 replacement after tendon maturation, indicating that PIEZO1 could be a target for promoting physical performance by enhancing function in mature tendon. The frequency of E756del PIEZO1 was higher in sprinters than in population-matched nonathletic controls in a small Jamaican cohort, suggesting a similar function in humans. Together, this human and mouse genetic and physiological evidence revealed a critical function of tendons in physical performance, which is tightly and robustly regulated by PIEZO1 in tenocytes.
  • Gen Matsumae, Mohamad Alaa Terkawi, Takayuki Nonoyama, Takayuki Kurokawa, Daisuke Takahashi, Tomohiro Shimizu, Ken Kadoya, Jian Ping Gong, Kazunori Yasuda, Norimasa Iwasaki
    Biomaterials science 10 (9) 2182 - 2187 2022/05/04 [Refereed]
     
    Double network hydrogels (DN gels) composed of poly (2-acrylamido-2-methyl propanesulfonic acid) (PAMPS) as the brittle first network and poly (N,N-dimethylacrylamide) (PDMA) as the ductile second network have been proven to be a substitute biomaterial for cartilage, with promising biocompatibility and low toxicity, when they are used as bulk materials. For their further applications as articular cartilages, it is essential to understand the biological reactions and adverse events that might be initiated by wear particles derived from these materials. In this study, we used DN gel micro-particles of sizes 4 μm and 10 μm generated by the grinding method to mimic wearing debris of DN gels. The biological responses to particles were then evaluated in a macrophage-cultured system and an inflammatory osteolysis murine model. Our results demonstrated that DN gel particles have the ability to activate macrophages and promote the expression of Tnf-α, both in vitro and in vivo. Furthermore, the implantation of these particles onto calvarial bone triggered local inflammation and bone loss in a mouse model. Our data reveal that the potential foreign body responses to the generated particles from artificial cartilage should receive more attention in artificial cartilage engineering with the goal of developing a safer biocompatible substitute.
  • 細胞外基質の電位変化に伴うJCウイルス増殖の制御
    谷川 聖, 野々山 貴行, 津田 真寿美, 王 磊, 種井 善一, Gong Jian Ping, 田中 伸哉
    日本病理学会会誌 (一社)日本病理学会 111 (1) 263 - 263 0300-9181 2022/03
  • 細胞外基質の電位変化に伴うJCウイルス増殖の制御
    谷川 聖, 野々山 貴行, 津田 真寿美, 王 磊, 種井 善一, Gong Jian Ping, 田中 伸哉
    日本病理学会会誌 (一社)日本病理学会 111 (1) 263 - 263 0300-9181 2022/03
  • Daisuke Ukeba, Katsuhisa Yamada, Takashi Suyama, Darren R Lebl, Takeru Tsujimoto, Takayuki Nonoyama, Hirokazu Sugino, Norimasa Iwasaki, Masatoki Watanabe, Yumi Matsuzaki, Hideki Sudo
    EBioMedicine 76 103845 - 103845 2022/01/24 [Refereed]
     
    BACKGROUND: Lumbar intervertebral disc (IVD) herniations are associated with significant disability. Discectomy is the conventional treatment option for IVD herniations but causes a defect in the IVD, which has low self-repair ability, thereby representing a risk of further IVD degeneration. An acellular, bioresorbable, and good manufacturing practice (GMP)-compliant in situ-forming gel, which corrects discectomy-associated IVD defects and prevents further IVD degeneration had been developed. However, this acellular matrix-based strategy has certain limitations, particularly in elderly patients, whose tissues have low self-repair ability. The aim of this study was to investigate the therapeutic efficacy of using a combination of newly-developed, ultra-purified, GMP-compliant, human bone marrow mesenchymal stem cells (rapidly expanding clones; RECs) and the gel for IVD regeneration after discectomy in a sheep model of severe IVD degeneration. METHODS: RECs and nucleus pulposus cells (NPCs) were co-cultured in the gel. In addition, RECs combined with the gel were implanted into IVDs following discectomy in sheep with degenerated IVDs. FINDINGS: Gene expression of NPC markers, growth factors, and extracellular matrix increased significantly in the co-culture compared to that in each mono-culture. The REC and gel combination enhanced IVD regeneration after discectomy (up to 24 weeks) in the severe IVD degeneration sheep model. INTERPRETATION: These findings demonstrate the translational potential of the combination of RECs with an in situ-forming gel for the treatment of herniations in degenerative human IVDs. FUNDING: Ministry of Education, Culture, Sports, Science, and Technology of Japan, Japan Agency for Medical Research and Development, and the Mochida Pharmaceutical Co., Ltd.
  • Takuma Kaibara, Lei Wang, Masumi Tsuda, Takayuki Nonoyama, Takayuki Kurokawa, Norimasa Iwasaki, Jian Ping Gong, Shinya Tanaka, Kazunori Yasuda
    Journal of biomedical materials research. Part A 110 (4) 747 - 760 2021/10/28 [Refereed]
     
    Recently, we have developed a hydroxyapatite (HAp)-hybridized double-network (DN) hydrogel (HAp/DN gel), which can robustly bond to the bone tissue in the living body. The purpose of this study is to clarify whether the HAp/DN gel surface can differentiate the bone marrow-derived mesenchymal stem cells (MSCs) to osteogenic cells. We used the MSCs which were harvested from the rabbit bone marrow and cultured on the polystyrene (PS) dish using the autogenous serum-supplemented medium. First, we confirmed the properties of MSCs by evaluating colony forming unit capacity, expression of MSC markers using flow cytometry, and multidifferential capacity. Secondly, polymerase chain reaction analysis demonstrated that the HAp/DN gel surface significantly enhanced mRNA expression of the eight osteogenic markers (TGF-β1, BMP-2, Runx2, Col-1, ALP, OPN, BSP, and OCN) in the cultured MSCs at 7 days than the PS surfaces (p < 0.0001), while the DN gel and HAp surfaces provided no or only a slight effect on the expression of these markers except for Runx2. Additionally, the alkaline phosphatase activity was significantly higher in the cells cultured on the HAp/DN gel surface than in the other three material surfaces (p < 0.0001). Thirdly, when the HAp/DN gel plug was implanted into the rabbit bone marrow, MSC marker-positive cells were recruited in the tissue generated around the plug at 3 days, and Runx2 and OCN were highly expressed in these cells. In conclusion, this study demonstrated that the HAp/DN gel surface can differentiate the MSCs into osteogenic cells.
  • Takayuki Nonoyama, Lei Wang, Ryuji Kiyama, Naohiro Kashimura, Kazunori Yasuda, Shinya Tanaka, Takayuki Kurokawa, Jian Ping Gong
    JOURNAL OF THE CERAMIC SOCIETY OF JAPAN 129 (9) 584 - 589 1882-0743 2021/09 [Refereed][Not invited]
     
    Double network (DN) hydrogels, possessing biocompatibility, low sliding friction, high strength and toughness, are promising as artificial cartilages for next-generation joint disease treatment. For such application, a fast and robust fixation of DN hydrogel to bone tissue in vivo is indispensable. However, bonding the DN hydrogel that contains similar to 90 wt % of water to bone is a grand challenge since glues do not work on hydrated surfaces. Recently, we reported that a DN hydrogel of its subsurface hybridized with low crystalline hydroxyapatite (HAp) can achieve robust fixation to bone after 4 weeks implantation in rabbit knees, owing to the HAp-induced osteogenesis penetration into the hydrogel matrix. For clinical application, achieving a quick fixation at the early stage of implantation remains as a next subject. In this study, instead of HAp, we hybridized calcium monohydrogen phosphate (monetite), which is a HAp precursor calcium phosphate salt, in the subsurface of the DN hydrogel and we observed an increase in the pushout resistance of the DN hydrogel to bone after 1 week implantation, prior to the HAp-induced osteogenesis penetration. In physiological environment, the monetite hybridized in the subsurface of the DN gel spontaneously dissolved to calcium and phosphate ions and then recrystallized to more stable HAp. We consider that the HAp formed in the boundary between the gel and the bone forms physical interlocking that significantly enhances the frictional resistance against the pushout force. The fast temporally pre-fixation to the bone by monetite surface hybridization makes one step closer to the clinical application of the DN gels as artificial cartilages. (C) 2021 The Ceramic Society of Japan. All rights reserved.
  • 甲斐原 拓真, 王 磊, 津田 真寿美, 野々山 貴行, 黒川 孝幸, きょう 剣萍, 岩崎 倫政, 田中 伸哉, 安田 和則
    日本整形外科学会雑誌 (公社)日本整形外科学会 95 (8) S1561 - S1561 0021-5325 2021/08
  • Liang Xu, Atsushi Urita, Tomohiro Onodera, Ryosuke Hishimura, Takayuki Nonoyama, Masanari Hamasaki, Dawei Liang, Kentaro Homan, Jian Ping Gong, Norimasa Iwasaki
    The American Journal of Sports Medicine 036354652110141 - 036354652110141 0363-5465 2021/06/01 [Refereed]
     
    Background: Ultrapurified alginate (UPAL) gel implantation has been demonstrated as effective in cartilage repair for osteochondral defects; however, cell transplantation within UPAL gels would be required to treat larger defects. Hypothesis: The combination of UPAL gel and bone marrow aspirate concentrate (BMAC) would enhance cartilage repair and subchondral bone repair for large osteochondral defects. Study Design: Controlled laboratory study. Methods: A total of 104 osteochondral defects (1 defect per knee) of 52 rabbits were randomly divided into 4 groups (26 defects per group): defects without any treatment (Defect group), defects treated using UPAL gel alone (UPAL group), defects treated using UPAL gel containing allogenic bone marrow mesenchymal stromal cells (UPAL-MSC group), and defects treated using UPAL gel containing BMAC (UPAL-BMAC group). At 4 and 16 weeks postoperatively, macroscopic and histologic evaluations and measurements of repaired subchondral bone volumes of reparative tissues were performed. Collagen orientation and mechanical properties of the reparative tissue were assessed at 16 weeks. Results: The defects in the UPAL-BMAC group were repaired with hyaline-like cartilage with well-organized collagen structures. The histologic scores at 4 weeks were significantly higher in the UPAL-BMAC group (16.9 ± 2.0) than in the Defect group (4.7 ± 1.9; P < .05), the UPAL group (10.0 ± 3.3; P < .05), and the UPAL-MSC group (12.2 ± 2.9; P < .05). At 16 weeks, the score in the UPAL-BMAC group (24.4 ± 1.7) was significantly higher than those in the Defect group (9.0 ± 3.7; P < .05), the UPAL group (14.2 ± 3.9; P < .05), and the UPAL-MSC group (16.3 ± 3.6; P < .05). At 4 and 16 weeks, the macroscopic evaluations were significantly superior in the UPAL-BMAC group compared with the other groups, and the values of repaired subchondral bone volumes in the UPAL-BMAC group were significantly higher than those in the Defect and UPAL groups. The mechanical properties of the reparative tissues were significantly better in the UPAL-BMAC group than in the other groups. Conclusion: The implantation of UPAL gel containing BMAC-enhanced hyaline-like cartilage repair and subchondral bone repair of osteochondral defects in a rabbit knee model. Clinical Relevance: These data support the potential clinical application of 1-step treatment for large osteochondral defects using biomaterial implantation with cell transplantation.
  • Takayuki Nonoyama, Jian Ping Gong
    Annual review of chemical and biomolecular engineering 2021/03/26 [Refereed]
     
    Soft and wet hydrogels have many similarities to biological tissues, though their mechanical fragility had been one of the biggest obstacles in biomedical applications. Studies and developments in double network (DN) hydrogels have elucidated how to create tough gels universally based on sacrificial bond principles and opened a path for biomedical application of hydrogels in regenerative medicine and artificial soft connective tissues, such as cartilage, tendon, and ligament, which endure high tension and compression. This review explores a universal toughening mechanism for and biomedical studies of DN hydrogels. Moreover, because the term sacrificial bonds has been mentioned often in studies of bone tissues, consisting of biomacromolecules and biominerals, recent studies of gel-biomineral composites to understand early-stage osteogenesis and to simulate bony sacrificial bonds are also summarized. Expected final online publication date for the Annual Review of Chemical and Biomolecular Engineering, Volume 12 is June 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
  • Daisuke Ukeba, Katsuhisa Yamada, Takeru Tsujimoto, Katsuro Ura, Takayuki Nonoyama, Norimasa Iwasaki, Hideki Sudo
    The Journal of bone and joint surgery. American volume 103 (8) e31  2021/01/21 [Refereed]
     
    BACKGROUND: The current surgical procedure of choice for intervertebral disc (IVD) herniation is discectomy, which induces postoperative IVD degeneration. Thus, cell-based therapies, as a 1-step simple procedure, are desired because of the poor capacity of IVDs for self-repair. The aim of this study was to investigate the repair efficacy of ultra-purified alginate (UPAL) gels containing bone marrow aspirate concentrate (BMAC) for the treatment of discectomy-associated IVD degeneration in rabbits. METHODS: The mechanical properties of 3 types of gels-UPAL, UPAL containing bone marrow-derived mesenchymal stem cells (BMSCs), and UPAL containing BMAC-were evaluated. Forty rabbits were assigned to 5 groups: intact control, discectomy (to make the cavity), UPAL (implantation of the UPAL gel after discectomy), BMSCs-UPAL (implantation of a combination of autogenic BMSCs and UPAL gel after discectomy), and BMAC-UPAL (implantation of a combination of BMAC and UPAL gel after discectomy). The gels were implanted at 4 weeks after induction of IVD degeneration. At 4 and 12 weeks, magnetic resonance imaging (MRI) as well as histological and immunohistochemical analyses were performed to analyze IVD degeneration qualitatively and the viability of the implanted cells. RESULTS: There was no significant difference among the 3 types of gels in terms of the results of unconfined compression tests. The implanted cells survived for 12 weeks. The histological grades of the BMSCs-UPAL (mean and standard deviation, 2.50 ± 0.53; p < 0.001) and BMAC-UPAL (2.75 ± 0.64, p = 0.001) showed them to be more effective in preventing degeneration than UPAL gel alone (3.63 ± 0.52). The effectiveness of BMAC-UPAL was not significantly different from that of BMSCs-UPAL, except with respect to type-II collagen synthesis. CONCLUSIONS: BMAC-UPAL significantly enhanced the repair of IVD defects created by discectomy. This approach could be an effective therapeutic strategy owing to its simplicity and cost-effectiveness compared with cell therapy using culture-expanded BMSCs. CLINICAL RELEVANCE: Local administration of the BMAC combined with UPAL gel could be an effective therapeutic strategy to enhance IVD repair after discectomy.
  • Takayuki Nonoyama, Lei Wang, Masumi Tsuda, Yuki Suzuki, Ryuji Kiyama, Kazunori Yasuda, Shinya Tanaka, Kousuke Nagata, Ryosuke Fujita, Naoya Sakamoto, Noriyuki Kawasaki, Hisayoshi Yurimoto, Jian Ping Gong
    Advanced healthcare materials 10 (3) e2001731  2020/11/16 [Refereed]
     
    Tough double network (DN) hydrogels are promising substitutes of soft supporting tissues such as cartilage and ligaments. For such applications, it is indispensable to robustly fix the hydrogels to bones with medically feasible methods. Recently, robustly bonding the DN hydrogels to defected bones of rabbits in vivo has been proved successful. The low crystalline hydroxyapatite (HAp) of calcium-phosphate-hydroxide salt coated on the surface layer of the DN hydrogels induced spontaneous osteogenesis penetrating into the semi-permeable hydrogels to form a gel/bone composite layer. In this work, the 44 Ca isotope-doped HAp/DN hydrogel is implanted in a defect of rabbit femoral bone and the dynamic osteogenesis process at the gel/bone interface is analyzed by tracing the calcium isotope ratio using isotope microscopy. The synthetic HAp hybridized on the surface layer of DN gel dissolves rapidly in the first two weeks by inflammation, and then the immature bone with a gradient structure starts to form in the gel region, reutilizing the dissolved Ca ions. These results reveal, for the first time, that synthetic HAp is reutilized for osteogenesis. These facts help to understand the lifetime of bone absorbable materials and to elucidate the mechanism of spontaneous, non-toxic, but strong fixation of hydrogels to bones.
  • Tomáš Sedlačík, Takayuki Nonoyama, Honglei Guo, Ryuji Kiyama, Tasuku Nakajima, Yoshihiro Takeda, Takayuki Kurokawa, Jian Ping Gong
    Chemistry of Materials 32 (19) 8576 - 8586 0897-4756 2020/10/13 [Refereed]
     
    Copyright © 2020 American Chemical Society. Supermacroporous hydrogels, possessing a spongelike structure and permeability, have drawn significant attention for their bioengineering and biomedical applications. However, their mechanical weakness due to the low-density structure is one of their biggest limitations. This work reports a multistep cryogelation technique, which does not require special equipment, for preparing tough supermacroporous hydrogels on the basis of the double-network (DN) strategy. The produced supermacroporous DN gels possess interconnected pores with pore sizes of 50-230 μm. They also show a compressive modulus of up to ∼100 kPa, which is 2-4 times higher than that of the corresponding supermacroporous single-network (SN) gels, and a compressive strength of up to 1 MPa at 80% compression. The supermacroporous DN cryogels are also stretchable with a work of extension of up to 38 kJ m-3, which is 1-2 orders larger than that of the SN cryogels. Their high stiffness and stretchability distinguish them from other types of cryogels. Supermacroporous triple-network (TN) gels and DN gels composed of different polymer combinations are also prepared. The technique presented herein is suitable for preparing supermacroporous DN gels from various polymers; hence, it is promising in meeting bioengineering and biomedical demands.
  • Junchao Huang, Martin Frauenlob, Yuki Shibata, Lei Wang, Tasuku Nakajima, Takayuki Nonoyama, Masumi Tsuda, Shinya Tanaka, Takayuki Kurokawa, Jian Ping Gong
    Biomacromolecules 21 (10) 4220 - 4230 2020/09/16 [Refereed][Not invited]
     
    Chitin is a biopolymer which has been proved to be a candidate as biomedical materials, yet the weak mechanical properties limited their potentials seriously. In this work, a chitin-based double-network (DN) hydrogel was designed as a potential superficial repairing material. The hydrogel was synthesized through double-network (DN) strategy composing hybrid regenerated chitin nanofibers (RCNs)-poly (ethylene glycol diglycidyl ether) (PEGDE) as the first network and polyacrylamide (PAAm) as the second network. The hybrid RCNs-PEGDE/PAAm DN hydrogel was strong and tough, possessing Young's modulus (elasticity) E 0.097 ± 0.020 MPa, fracture stress σf 0.449 ± 0.025 MPa, and work of fracture Wf 5.75 ± 0.35 MJ·m-3. The obtained DN hydrogel was strong enough for surgical requirements in the usage of soft tissue scaffolds. In addition, the chitin endowed the DN hydrogel with good bacteria resistance and accelerated fibroblast proliferation, which NIH3T3 cell number increased nearly 5 times within 3 days. Subcutaneous implantation studies showed that the DN hydrogel did not induce inflammation after 4 weeks, suggesting a good biosafety in vivo. These results indicated that the hybrid RCNs-PEGDE/PAAm DN hydrogel had great prospect as rapid soft tissue repairing materials.
  • Kazuki Fukao, Kazuki Tanaka, Ryuji Kiyama, Takayuki Nonoyama, Jian Ping Gong
    Journal of materials chemistry. B 2020/05/15 [Refereed][Not invited]
     
    Inspired by bone tissues, we mineralized low crystalline hydroxyapatite (HAp) particles in double network (DN) hydrogels, and we observed that the HAp minerals toughen the gels. The contribution of dissipated energy from HAp minerals was over 500% higher than that from the polymer during tensile deformation. We elucidated that the amorphous parts in the HAp minerals break at deformation, acting as energy-dissipative sacrificial bonds. This result implies that not only brittle polymer networks but also minerals can provide sacrificial bonds to toughen soft materials.
  • Meet the phase-separation polymeric gel
    Takayuki Nonoyama, Jian Ping Gong
    The Innovation Platform 1 73 - 74 2020/03 [Not refereed][Invited]
  • Honglei Guo, Yuto Uehara, Takahiro Matsuda, Ryuji Kiyama, Long Li, Jamil Ahmed, Yoshinori Katsuyama, Takayuki Nonoyama, Takayuki Kurokawa
    Soft matter 16 (7) 1897 - 1907 2020/01/29 [Refereed][Not invited]
     
    Soft tissue engineering requires antifouling materials that are biocompatible and mechanically flexible. Conventional hydrogels containing more than 70 wt% water are thus promising antifouling material candidates. However, some hydrogels are difficult to apply in internal body organs because of undesirable protein absorption on their surfaces. Due to the lack of an effective method for observing the true charge densities of hydrogels, the reason why electrostatic interactions dominate protein absorption behavior remains unclear. In this work, we adopt the microelectrode technique (MET) to study the electrical potentials of hydrogels with negative, positive, and neutral potentials and demonstrate the protein absorption behaviors on those hydrogels. The results show that MET is an effective method to obtain the surface charge densities of various hydrogels. Furthermore, the amounts of absorbed proteins on the gels were quantified with respect to the charge densities of the hydrogels. The results indicate that electrostatic absorption is quantitatively dominated by a combination of hydrogel charge density and overall protein charge. Based on the knowledge obtained in this work, the effects of hydrogel surface charges on protein absorption can be better understood. Thus, the results are expected to promote the application of hydrogels in tissue engineering.
  • Nonoyama, T., Lee, Y.W., Ota, K., Fujioka, K., Hong, W., Gong, J.P.
    Advanced Materials 32 (4) e1905878  1521-4095 2020 [Refereed][Not invited]
  • Sedla?{\'i}k, T., Nonoyama, T., Guo, H., Kiyama, R., Nakajima, T., Takeda, Y., Kurokawa, T., Gong, J.P.
    Chemistry of Materials 32 (24) 10737 - 10737 1520-5002 2020
  • Takayuki Nonoyama
    Polymer Journal 0032-3896 2020 [Refereed][Invited]
     
    © 2020, The Society of Polymer Science, Japan. Due to the soft and wet characteristics of hydrogels that acquire high mechanical strength by toughening strategies, tough and robust hydrogels are attractive as next-generation structural biomaterials, especially for the substitution of soft connective tissues such as cartilage, tendons, and ligaments. Firm fixation of the gels to bone in vivo is an indispensable technology in clinical applications. However, since the surface of the hydrogel is very watery, current medical adhesives cannot fix the gels at all. In this review, first, the double network (DN) strategy, a universal method to toughen hydrogels, is presented. Second, by combining hydroxyapatite (HAp) of a main bony inorganic component with a high-strength DN gel, a biocompatible adhesion method accompanied by spontaneous osteogenesis penetration into the gel matrix is introduced. In addition, the HAp-gel composite can be used as a simplified model of bone tissues because of their similarity in terms of components. Third, HAp formation spatially confined by the polymer network of gel is shown as a model of the earliest stage of biomineralization in vivo. These studies on biomineral–hydrogel composites have great potential to contribute not only basic research on osteogenesis mechanisms but also clinical applications of tough hydrogels.
  • Kazuki Fukao, Tasuku Nakajima, Takayuki Nonoyama, Takayuki Kurokawa, Takahiko Kawai, Jian Ping Gong
    Macromolecules 0024-9297 2020 [Refereed][Not invited]
     
    Copyright © 2020 American Chemical Society. Double network hydrogels (DN gels) exhibit extraordinarily high strength and toughness by interplay of the two contrasting networks: the rigid, brittle network serves as a sacrificial bond that fractures at a relatively low strain, while the soft, stretchable network serves as hidden length that sustains stress by large extension afterward. The internal fracture process of the brittle network strongly depends on the relative strength of the two networks. In this study, we study the internal fracturing process of typical DN gels that show yielding or necking under uniaxial stretching using in situ small-angle X-ray scattering. Two samples consisting of the same brittle first network from poly(2-acrylamido-2-methylpropanesulfonic acid) but stretchable second network from poly(N,N-dimethylacrylamide) of different concentrations were adopted. We found that (1) the brittle network shows nonaffine deformation even far below the yield strain by local fracture; (2) for the sample of low second network concentration, significant strain amplification occurs around the submicrometer-scale voids (defects) preexisting in the brittle network, which induces the fracture percolation of brittle network from voids to show the necking phenomenon; and (3) the strain amplification at voids is suppressed in the sample of high second network concentration, and fracture of brittle network occurs dispersedly, showing yielding without necking.
  • Cui Kunpeng, Ye Ya Nan, Sun Tao Lin, Chen Liang, Li Xueyu, Kurokawa Takayuki, Nakajima Tasuku, Nonoyama Takayuki, Gong Jian Ping
    MACROMOLECULES 52 (19) 7369 - 7378 0024-9297 2019/10/08 [Refereed][Not invited]
     
    Recent studies reported a multiscale structure in tough and self-healing hydrogels containing physical associations. For example, a type of tough and self-healing hydrogel from charge-balanced polyampholytes (PA) has a mesoscale bicontinuous double network structure with structural length around 400 nm. This mesoscale network structure plays an essential role in the multistep rupture process, which leads to the high toughness of PA hydrogels. In this work, by using an osmotic stress method, we symmetrically studied how the relative strength of soft and hard networks and the strength of ionic bonds influence the property of PA gels. We found that increasing osmotic stress of the bath solution triggers the structure transition from bicontinuous double network structure to a homogeneous structure, which drives the concurrently opaque-transparent transition in optical property and viscoelastic-glassy transition in mechanical behavior. The gels around the structural transition point were found to possess both high toughness (fracture energy of 7200 J m(-2)) and high stiffness (Young's modulus of 12.9 MPa), which is a synergy of soft network and hard network of the bicontinuous structure. Our work not only provides an approach to tune the structure and property of physical hydrogels through tuning physical association but also gives a demo to investigate their relationships, yet another step forward gives inspiration to design a new type of tough and self-healing materials around the structural transition point.
  • Murai, J., Nakajima, T., Matsuda, T., Tsunoda, K., Nonoyama, T., Kurokawa, T., Gong, J.P.
    Polymer 178 0032-3861 2019/09/12 [Refereed][Not invited]
  • Zhang Hui Jie, Luo Feng, Ye Yanan, Sun Tao Lin, Nonoyama Takayuki, Kurokawa Takayuki, Nakajima Tasuku
    ACS APPLIED POLYMER MATERIALS 1 (8) 1948 - 1953 2637-6105 2019/08 [Refereed][Not invited]
     
    Tough triblock copolymer hydrogels with microstructures of sphere, cylinder, and laminae were constructed using a newly developed "drying and swelling" method without changing the chemical structures of their monomeric units. These tough triblock copolymer hydrogels commonly showed high fracture stress of similar to 10 MPa but exhibited varied elastic moduli depending on their microstructures. Furthermore, the constructed laminar gel formed pH-sensitive photonic gel at the base conditions, providing the gel application with potential as a sensor. Given their high toughness, biocompatibility, and tunable modulus, this study helps expand the potential application of amphiphilic block copolymer hydrogels for medical and industrial use.
  • Ryosuke Hishimura, Tomohiro Onodera, Kazutoshi Hontani, Rikiya Baba, Kentaro Homan, Shinji Matsubara, Zenta Joutoku, WooYoung Kim, Takayuki Nonoyama, Takayuki Kurokawa, Jian Ping Gong, Norimasa Iwasaki
    The American journal of sports medicine 47 (2) 468 - 478 0363-5465 2019/02 [Refereed][Not invited]
     
    BACKGROUND: One of the most important limitations of osteochondral autograft transplantation (OAT) is the adverse effect on donor sites in the knee. To decrease the number and/or size of osteochondral defects, we devised a method with biomaterial implantation after OAT. HYPOTHESIS: OAT augmented by ultrapurified alginate (UPAL) gel enhances cartilage repair capacity. STUDY DESIGN: Controlled laboratory study. METHODS: Seventy-five osteochondral defects in rabbits were divided into 3 groups: osteochondral defects with OAT alone, defects with OAT augmented by UPAL gel (combined group), and defects without intervention as controls. Macroscopic and histological evaluations of the reparative tissues were performed at 4 and 12 weeks postoperatively. Histological evaluation of graft cartilage degradation was also performed. To evaluate the effects of UPAL gel on graft healing, repaired bone volumes and osseointegration of the graft were evaluated. Collagen orientation and the mechanical properties of the reparative tissue and graft cartilage were also evaluated qualitatively. RESULTS: The macroscopic and histological evaluations of the combined group were significantly superior to the other groups at 12 weeks postoperatively. Regarding degenerative change of the graft, the histological scores of the combined group were significantly higher than those of the OAT-alone group. The values of repaired subchondral bone volumes and osseointegration of the graft were almost identical in both groups. Collagen orientation and the mechanical properties of the reparative tissue and graft cartilage were significantly better in the combined group than in the other groups. CONCLUSION: Administration of UPAL gel in OAT enhanced cartilage repair and protected graft cartilage without inhibiting subchondral bone repair and graft survival. CLINICAL RELEVANCE: OAT augmented by UPAL gel decreases the number and/or size of osteochondral grafts, minimizing the risk of donor site morbidity. This combination technique has the potential to improve clinical outcomes and expand the surgical indications for OAT.
  • Takahashi, R., Shimano, K., Okazaki, H., Kurokawa, T., Nakajima, T., Nonoyama, T., King, D.R., Gong, J.P.
    Advanced Materials Interfaces 5 (23) 2196-7350 2018/12/07 [Refereed][Not invited]
  • Takeru Tsujimoto, Hideki Sudo, Masahiro Todoh, Katsuhisa Yamada, Koji Iwasaki, Takashi Ohnishi, Naoki Hirohama, Takayuki Nonoyama, Daisuke Ukeba, Katsuro Ura, Yoichi M Ito, Norimasa Iwasaki
    EBioMedicine 37 521 - 534 2018/11 [Refereed][Not invited]
     
    BACKGROUND: The current surgical procedure of choice for lumbar intervertebral disc (IVD) herniation is discectomy. However, defects within IVD produced upon discectomy may impair tissue healing and predispose patients to subsequent IVD degeneration. This study aimed to investigate whether the use of an acellular bioresorbable ultra-purified alginate (UPAL) gel implantation system is safe and effective as a reparative therapeutic strategy after lumbar discectomy. METHODS: Human IVD cells were cultured in a three-dimensional system in UPAL gel. In addition, lumbar spines of sheep were used for mechanical analysis. Finally, the gel was implanted into IVD after discectomy in rabbits and sheep in vivo. FINDINGS: The UPAL gel was biocompatible with human IVD cells and promoted extracellular matrix production after discectomy, demonstrating sufficient biomechanical characteristics without material protrusion. INTERPRETATION: The present results indicate the safety and efficacy of UPAL gels in a large animal model and suggest that these gels represent a novel therapeutic strategy after discectomy in cases of lumbar IVD herniation. FUND: Grant-in-Aid for the Ministry of Education, Culture, Sports, Science, and Technology of Japan, Japan Agency for Medical Research and Development, and the Mochida Pharmaceutical Co., Ltd.
  • Kiyama R, Nonoyama T, Wada S, Semba S, Kitamura N, Nakajima T, Kurokawa T, Yasuda K, Tanaka S, Gong JP
    Acta biomaterialia 81 60 - 69 1742-7061 2018/10 [Refereed][Not invited]
     
    Mechanically robust hydrogels are promising biomaterials as artificial supportive tissue. These applications require selective and robust bonding of the hydrogels to living tissue. Recently, we achieved strong in vivo bone bonding of a tough double network (DN) hydrogel, a potential material for use as artificial cartilage and tendon, by hybridizing osteoconductive hydroxyapatite (HAp) in the gel surface layer. In this work, we report micro patterning of HAp at the surface of the DN hydrogel for selective osteoconduction. Utilizing the dissolution of HAp in an acidic environment, the soft lithography technique using an acid gel stamp was adopted to form a high-resolution HAp pattern on the gel. The HAp-patterned gel showed well-regulated migration and adhesion of cells in vitro. Moreover, the HAp-patterned gel showed selective and robust bonding to the rabbit bone tissue in vivo. This HAp soft lithography technique allows for simple and quick preparation of tailor-made osteoconductive hydrogels and can be applied to other hydrogels for selective bone bonding. STATEMENT OF SIGNIFICANCE: Hydrogels, preserving large amount of water, have been studied for next-generation artificial soft tissues. However, fixation of hydrogels to living tissue was unsolved issue for clinical application. Recently, we achieved robust bonding of a tough double network gel to bone in vivo by coating of osteoconductive hydroxyapatite in the gel surface layer. For further progress for practical use, we report the micro patterning of HAp at the surface of the DN hydrogel by using soft lithography technique, to perform selective bonding to only objective area without unnecessary coalescence. The HAp lithography technique is simple, quick and non-toxic method to prepare tailor-made osteoconductive hydrogels and has universality of species of hydrogels.
  • Ye Ya Nan, Frauenlob Martin, Wang Lei, Tsuda Masumi, Sun Tao Lin, Cui Kunpeng, Takahashi Riku, Zhang Hui Jie, Nakajima Tasuku, Nonoyama Takayuki, Kurokawa Takayuki, Tanaka Shinya, Gong Jian Ping
    ADVANCED FUNCTIONAL MATERIALS 28 (31) 1616-301X 2018/08/01 [Refereed][Not invited]
     
    Tough and self-recoverable hydrogel membranes with micrometer-scale thickness are promising for biomedical applications, which, however, rarely be realized due to the intrinsic brittleness of hydrogels. In this work, for the first time, by combing noncovalent DN strategy and spin-coating method, we successfully fabricated thin (thickness: 5-100 mu m), yet tough (work of extension at fracture: 10(5)-10(7) J m(-3)) and 100% self-recoverable hydrogel membranes with high water content (62-97 wt%) in large size (approximate to 100 cm(2)). Amphiphilic triblock copolymers, which form physical gels by self-assembly, were used for the first network. Linear polymers that physically associate with the hydrophilic midblocks of the first network, were chosen for the second network. The inter-network associations serve as reversible sacrificial bonds that impart toughness and self-recovery properties on the hydrogel membranes. The excellent mechanical properties of these obtained tough and thin gel membranes are comparable, or even superior to many biological membranes. The in vitro and in vivo tests show that these hydrogel membranes are biocompatible, and postoperative nonadhesive to neighboring organs. The excellent mechanical and biocompatible properties make these thin hydrogel membranes potentially suitable for use as biological or postoperative antiadhesive membranes.
  • Md. Tariful Islam Mredha, Yun Zhou Guo, Takayuki Nonoyama, Tasuku Nakajima, Takayuki Kurokawa, Jian Ping Gong
    Advanced Materials 30 (9) 1521-4095 2018/03/01 [Refereed][Not invited]
     
    Natural structural materials (such as tendons and ligaments) are comprised of multiscale hierarchical architectures, with dimensions ranging from nano- to macroscale, which are difficult to mimic synthetically. Here a bioinspired, facile method to fabricate anisotropic hydrogels with perfectly aligned multiscale hierarchical fibrous structures similar to those of tendons and ligaments is reported. The method includes drying a diluted physical hydrogel in air by confining its length direction. During this process, sufficiently high tensile stress is built along the length direction to align the polymer chains and multiscale fibrous structures (from nano- to submicro- to microscale) are spontaneously formed in the bulk material, which are well-retained in the reswollen gel. The method is useful for relatively rigid polymers (such as alginate and cellulose), which are susceptible to mechanical signal. By controlling the drying with or without prestretching, the degree of alignment, size of superstructures, and the strength of supramolecular interactions can be tuned, which sensitively influence the strength and toughness of the hydrogels. The mechanical properties are comparable with those of natural ligaments. This study provides a general strategy for designing hydrogels with highly ordered hierarchical structures, which opens routes for the development of many functional biomimetic materials for biomedical applications.
  • Md. Anamul Haque, Kei Mito, Takayuki Kurokawa, Tasuku Nakajima, Takayuki Nonoyama, Muhammad Ilyas, Jian Ping Gong
    ACS Omega 3 (1) 55 - 62 2470-1343 2018 [Refereed][Not invited]
     
    One-dimensional photonic crystals or multilayer films produce colors that change depending on viewing and light illumination angles because of the periodic refractive index variation in alternating layers that satisfy Bragg’s law. Recently, we have developed multilayered photonic hydrogels of two distinct bulk geometries that possess an alternating structure of a rigid polymeric lamellar bilayer and a ductile polyacrylamide (PAAm) matrix. In this paper, we focus on fabrication of composite gels with variable photonic band gaps by controlling the PAAm layer thickness. We report programmable angle-dependent and angle-independent structural colors produced by composite hydrogels, which is achieved by varying bulk and internal geometries. In the sheet geometry, where the lamellae are aligned parallel to the sheet surface, the photonic gel sheet exhibits strong angle-dependent colors. On the other hand, when lamellae are coaxially aligned in a cylindrical geometry, the gel rod exhibits an angle-independent color, in sharp contrast with the gel sheet. Rocking curves have been constructed to justify the diverse angle-dependent behavior of various geometries. Despite varying the bulk geometry, the tunable photonic gels exhibit strong mechanical performances and toughness. The distinct angle dependence of these tough photonic materials with variable band gaps could benefit light modulation in displays and sensor technologies.
  • Kazuki Fukao, Takayuki Nonoyama, Ryuji Kiyama, Kazuya Furusawa, Takayuki Kurokawa, Tasuku Nakajima, Jian Ping Gong
    ACS Nano 11 (12) 12103 - 12110 1936-086X 2017/12/26 [Refereed][Not invited]
     
    Bone tissues possess excellent mechanical properties such as compatibility between strength and flexibility and load bearing owing to the hybridization of organic/inorganic matters with anisotropic structure. To synthetically mimic such an anisotropic structure of natural organic/inorganic hybrid materials, we carried out hydroxyapatite (HAp) mineralization in stretched tough double network (DN) hydrogels. Anisotropic mineralization of HAp took place in stretched hydrogels, as revealed by high brightness synchrotron X-ray scattering and transmission electron microscopic observation. The c-axis of mineralized HAp aligned along the stretching direction, and the orientation degree S calculated from scattering profiles increased with increasing in the elongation ratio λ of the DN gel, and S at λ = 4 became comparable to that of rabbit tibial bones. The morphology of HAp polycrystal gradually changed from spherical to unidirectional rod-like shape with increased elongation ratio. A possible mechanism for the anisotropic mineralization is proposed, which would be one of the keys to develop mechanically anisotropic organic/inorganic hybrid materials.
  • Muhammad Ilyas, Md. Anamul Haque, Youfeng Yue, Takayuki Kurokawa, Tasuku Nakajima, Takayuki Nonoyama, Jian Ping Gong
    MACROMOLECULES 50 (20) 8169 - 8177 0024-9297 2017/10 [Refereed][Not invited]
     
    We study the effect of dehydration On the structure and mechanical properties of anisotropic lamellar hydrogels, consisting of alternative stacking of several thousands of nanoscale rigid bilayers from amphiphilic poly(dodecyl glyceryl itaconate) (PDGI) and submicroscale soft hydrogel layers from hydrophilic polyacrylamide (PAAm) networks. We found that the layered microstructure is well preserved with dehydration, and a ductile-brittle transition occurs at the critical water-content. This, transition is related to the rubbery-glassy transition of the PAAm layers, which occurs at 58 wt % water content and is much higher than 26 wt% of bulk PAAm hydrogels. Such specific behavior of the lamellar hydrogels indicates that the dynamics of the submicroscale PAAm hydrated layer intercalated between the rigid bilayers are very different from its bulk state.
  • Kei Mito, Md. Anamul Haque, Tasuku Nakajima, Maki Uchiumi, Takayuki Kurokawa, Takayuki Nonoyama, Jian Ping Gong
    POLYMER 128 373 - 378 0032-3861 2017/10 [Refereed][Not invited]
     
    Novel, supramolecular, anisotropic hydrogels (called MC-PDGI gels) are presented in this study. These MC-PDGI gels consist of multi-cylindrical lipid bilayers aligned in a uniaxial manner and embedded in a soft hydrogel matrix. The bilayers and the hydrogel interact weakly due to hydrogen bonding. These MC-PDGI gels swell after exposure to water, which causes their volume and diameter to increase while simultaneously causing their length to decrease. This anisotropic swelling-induced contraction behavior is the result of competition between the isotropic elasticity of the hydrogel matrix and the interfacial tension of the lipid bilayers. Moreover, the MC-PDGI gels exhibit unique quasi one-dimensional diffusion behavior owing to the difficulty of molecular penetration through the multi-layered lipid bilayers. These materials would be useful for prolonged drug release or as an actuator. (C) 2017 Elsevier Ltd. All rights reserved.
  • Md. Tariful Islam Mredha, Nobuto Kitamura, Takayuki Nonoyama, Susumu Wada, Keiko Goto, Xi Zhang, Tasuku Nakajima, Takayuki Kurokawa, Yasuaki Takagi, Kazunori Yasuda, Jian Ping Gong
    BIOMATERIALS 132 85 - 95 0142-9612 2017/07 [Refereed][Not invited]
     
    Soft supporting tissues in the human body, such as cartilages and ligaments, are tough materials and firmly fixed to bones. These soft tissues, once injured, cannot regenerate spontaneously in vivo. Developing tough and biocompatible hydrogels as artificial soft supporting tissues would substantially improve outcomes after soft tissue injury. Collagen is the main rigid component in soft connective tissues which is organized in various hierarchical arrays. We have successfully developed a novel class of collagen fibril-based tough hydrogels based on the double network (DN) concept using swim bladder collagen (SBC) extracted from Bester sturgeon fish. The DN hydrogels, SBC/PDMAAm, are composed of physically/chemically crosslinked anisotropic SBC fibril as the first network and neutral, biocompatible poly(N,N'-dimethylacrylamide) (PDMAAm) as the second network. The anisotropic structure of SBC fibril network, which is well retained in the DN hydrogels, is formed by free injection method, taking advantage of the excellent fibrillogenesis capacity of SBC. The denaturation temperature of collagen is improved in the DN hydrogels. These DN gels possess anisotropic swelling behavior, exhibit excellent mechanical properties comparable to natural cartilage. The 4 weeks implantation of the gels in the osteochondral defect of rabbit knee also shows excellent biomechanical performance in vivo. Furthermore, the hydroxyapatite (HAp) coated DN gels, HAp/SBC/PDMAAm gels, strongly bond to bone after 4 weeks. This new class of collagen-based hybrid DN gels, as soft and elastic ceramics, having good biomechanical performance and strong bonding ability with bone would expand the choice for designing next generation orthopedic implants such as artificial cartilage, bone defect repair material in the load bearing region of the body. (C) 2017 Elsevier Ltd. All rights reserved.
  • Yiwan Huang, Daniel R. King, Tao Lin Sun, Takayuki Nonoyama, Takayuki Kurokawa, Tasuku Nakajima, Jian Ping Gong
    ADVANCED FUNCTIONAL MATERIALS 27 (9) 1605350  1616-301X 2017/03 [Refereed][Not invited]
     
    Tough hydrogels have shown strong potential as structural biomaterials. These hydrogels alone, however, possess limited mechanical properties (such as low modulus) when compared to some load-bearing tissues, e.g., ligaments and tendons. Developing both strong and tough soft materials is still a challenge. To overcome this obstacle, a new material design strategy has been recently introduced by combining tough hydrogels with woven fiber fabric to create fiber reinforced soft composites (FRSCs). The new FRSCs exhibit extremely high toughness and tensile properties, far superior to those of the neat components, indicating a synergistic effect. Here, focus is on understanding the role of energy dissipation of the soft matrix in the synergistic toughening of FRSCs. By selecting a range of soft matrix materials, from tough hydrogels to weak hydrogels and even a commercially available elastomer, the toughness of the matrix is determined to play a critical role in achieving extremely tough FRSCs. This work provides a good guide toward the universal design of soft composites with extraordinary fracture resistance capacity.
  • Double Networkゲルをマトリックスとした骨組織類似構造の創製
    深尾 一城, 野々山 貴行, 黒川 孝幸, 中島 祐, きょう 剣萍
    日本バイオマテリアル学会大会予稿集 日本バイオマテリアル学会 シンポジウム2016 237 - 237 2016/11
  • Susumu Wada, Nobuto Kitamura, Takayuki Nonoyama, Ryuji Kiyama, Takayuki Kurokawa, Jian Ping Gong, Kazunori Yasuda
    ACTA BIOMATERIALIA 44 125 - 134 1742-7061 2016/10 [Refereed][Not invited]
     
    We have developed a novel hydroxyapatite (HAp)-coated double-network (DN) hydrogel (HAp/DN gel). The purpose of this study was to determine details of the cell and tissue responses around the implanted HAp/DN gel and to determine how quickly and strongly the HAp/DN gel bonds to the bone in a rabbit osteochondral defect model. Immature osteoid tissue was formed in the space between the HAp/DN gel and the bone at 2 weeks, and the osteoid tissue was mineralized at 4 weeks. The push-out load of the HAp/DN gel averaged 37.54 N and 42.15 N at 4 and 12 weeks, respectively, while the push-out load of the DN gel averaged less than 5 N. The bonding area of the HAp/DN gel to the bone was above 80% by 4 weeks, and above 90% at 12 weeks. This study demonstrated that the HAp/DN gel enhanced osseointegration at an early stage after implantation. The presence of nanoscale structures in addition to osseointegration of HAp promoted osteoblast adhesion onto the surface of the HAp/DN gel. The HAp/DN gel has the potential to improve the implant-tissue interface in next-generation orthopaedic implants such as artificial cartilage. Statement of Significance Recent studies have reported the development of various hydrogels that are sufficiently tough for application as soft supporting tissues. However, fixation of hydrogels on bone surfaces with appropriate strength is a great challenge. We have developed a novel, tough hydrogel hybridizing hydroxyapatite (HAp/DN gel), which is directly bondable to the bone. The present study demonstrated that the HAp/DN gel enhanced osseointegration in the early stage after implantation. The presence of nanoscale structures in addition to the osseointegration ability of hydroxyapatite promoted osteoblast adhesion onto the surface of the HAp/DN gel. The HAp/DN gel has the potential to improve the implant-tissue interface in next-generation orthopaedic implants such as artificial cartilage. (C) 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
  • Kotaro Higa, Nobuto Kitamura, Takayuki Kurokawa, Keiko Goto, Susumu Wada, Takayuki Nonoyama, Fuminori Kanaya, Kazuyuki Sugahara, Jian Ping Gong, Kazunori Yasuda
    ACTA BIOMATERIALIA 43 38 - 49 1742-7061 2016/10 [Refereed][Not invited]
     
    The purpose of this study was to clarify fundamental mechanical properties and biological responses of the sodium hyaluronate-containing double network (HA-DN) gel and chondroitin sulfate-containing double network (CS-DN) gel, which were newly developed using the molecular stent method. This study discovered the following facts. First, these hydrogels had high mechanical performance comparable to the native cartilage tissue, and the mechanical properties were not affected by immersion in the saline solution for 12 weeks. Secondly, the mechanical properties of the CS-DN gel were not significantly reduced at 12 weeks in vivo, while the mechanical properties of the HA-DN gel were significantly deteriorated at 6 weeks. Thirdly, the degree of inflammation around the HA-DN gel was the same as that around the negative control. The CS-DN gel showed a mild but significant foreign body reaction, which was significantly greater than the negative control and less than the positive control at 1 week, while the inflammation was reduced to the same level as the negative control at 4 and 6 weeks. Fourthly, these gels induced differentiation of the ATDC5 cells into chondrocytes in the culture with the insulin free maintenance medium. These findings suggest that these tough hydrogels are potential biomaterials for future application to therapeutic implants such as artificial cartilage. Statement of Significance The present study reported fundamental biomaterial properties of the sodium hyaluronate-containing double network (HA-DN) gel and chondroitin sulfate-containing double network (CS-DN) gel, which were newly developed using the molecular stent method. Both the HA- and CS-DN gels had high mechanical properties comparable to the cartilage tissue and showed the ability to induce chondrogenic differentiation of ATDC5 cells in vitro. They are potential biomaterials that may meet the requirements of artificial cartilage concerning the material properties. Further, these DN gels can be also applied to the implantable inducer for cell-free cartilage regeneration therapy. (C) 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
  • 和田 進, 北村 信人, 野々山 貴行, 木山 竜二, 仙葉 愼吾, 小野寺 純, 横田 正司, 後藤 佳子, 比嘉 浩太郎, 黒川 孝幸, Gong Jian Ping, 安田 和則
    日本整形外科学会雑誌 (公社)日本整形外科学会 90 (8) S1598 - S1598 0021-5325 2016/08
  • Sadia Nazneen Karobi, Tao Lin Sun, Takayuki Kurokawa, Feng Luo, Tasuku Nakajima, Takayuki Nonoyama, Jian Ping Gong
    MACROMOLECULES 49 (15) 5630 - 5636 0024-9297 2016/08 [Refereed][Not invited]
     
    Polyampholyte (PA) hydrogels are a new class of tough and selfhealing supramolecular hydrogels that have a potential as load-bearing soft materials. Studying on the creep behavior of these hydrogels and understanding the molecular mechanism are important for prediction of lifetime of the materials. In the present work, we study the creep rupture dynamics of the PA hydrogels with and without chemical cross-linking, in a certain observation time window. We have found that above some critical loading stress both physical and lightly chemically cross-linked hydrogels undergo creep rupture while moderately chemically cross-linked hydrogel resists creep flow. To elucidate the molecular mechanism, we have further compared the creep behaviors of the physical and lightly chemically cross-linked samples. The creep rate of the samples decreases with the creep time, following a power law relation, regardless of the loading stress variation. The fracture time of both of these hydrogels exponentially decreases with the increase of the loading stress, following the same master curve at high loading stress region, while the behavior of the two samples becomes different in the low loading stress region. We have explained the delayed fracture dynamics at high loading stress region in terms of a relatively weak strong bond rupture mechanism.
  • Takayuki Nonoyama, Susumu Wada, Ryuji Kiyama, Nobuto Kitamura, Md. Tariful Islam Mredha, Xi Zhang, Takayuki Kurokawa, Tasuku Nakajima, Yasuaki Takagi, Kazunori Yasuda, Jian Ping Gong
    ADVANCED MATERIALS 28 (31) 6740 - + 0935-9648 2016/08 [Refereed][Not invited]
     
    On implanting hydroxyapatite-mineralized tough hydrogel into osteochondral defects of rabbits, osteogenesis spontaneously penetrates into the gel matrix owing to the semi-permeablility of the hydrogel. The gradient layer (around 40 mu m thick) contributes quite strong bonding of the gel to bone. This is the first success in realizing the robust osteointegration of tough hydrogels, and the method is simple and feasible for practical use.
  • Ao-kai Zhang, Jun Ling, Kewen Li, Guo-dong Fu, Tasuku Nakajima, Takayuki Nonoyama, Takayuki Kurokawa, Jian Ping Gong
    JOURNAL OF POLYMER SCIENCE PART B-POLYMER PHYSICS 54 (13) 1227 - 1236 0887-6266 2016/07 [Refereed][Not invited]
     
    In this study, controlled amount of dangling ends is introduced to the two series of poly(ethylene glycol)-based hydrogel networks with three and four crosslinking functionality by using click chemistry. The structure of the gels with regulated defect percentage is confirmed by comparing the results of low-field NMR characterization and Monte Carlo simulation. The mechanical properties of these gels were characterized by tensile stress-strain behaviors of the gels, and the results are analyzed by Gent model and Mooney-Rivlin model. The shear modulus of the swollen gels is found to be dependent on the functionality of the network, and decreases with the defect percentage. Furthermore, the value of shear modulus well obeys the Phantom model for all the gels with varied percentage of the defects. The maximum extension ratio, obtained from the fitting of Gent model, is also found to be dependent on the functionality of the network, and does not change with the defect percentage, except at very high defect percentage. The value of the maximum extension ratio is between that predicted from Phantom model and the Affine model. This indicates that at the large deformation, the fluctuation of the crosslinking points is suppressed for some extend but still exists. Polymer volume fractions at various defect percentages obtained from prediction of Flory-Rehner model are found to be in well agreement with the swelling experiment. All these results indicate that click chemistry is a powerful method to regulate the network structure and mechanical properties of the gels. (C) 2016 Wiley Periodicals, Inc.
  • Abu Bin Ihsan, Tao Lin Sun, Takayuki Kurokawa, Sadia Nazneen Karobi, Tasuku Nakajima, Takayuki Nonoyama, Chanchal Kumar Roy, Feng Luo, Jian Ping Gong
    MACROMOLECULES 49 (11) 4245 - 4252 0024-9297 2016/06 [Refereed][Not invited]
     
    Recently, polyampolytes have been discovered to form hydrogels that possess high toughness, full resilience, and self-healing between two cut surfaces. The self-healing of this class of hydrogels is based on the re-forming of the multiple Tonic bonds at the fractured surfaces, in which the mobility of the polymer segments and strength of the ionic bonds play an important role. In this work, we study the effects of healing temperature and chemistry of the polyampholyte hydrogels (chemical cross -linker density and chemical structure of the monomers) on the healing kinetics and healing efficiency. The high healing temperature substantially accelerates the self-healing kinetics. Chemical cross-linking reduces the self-healing efficiency. Monomers with more hydrophobic feature give a low self-healing efficiency. For polyampholyte physical hydrogels with a softening temperature below the room temperature, excellent-healing efficiency (similar to 84% on average and maximum 99%) was observed without any external stimuli.- We found a correlation between the self-healing efficiency and the fraction of dynamic bonds in the total bonds for relatively soft samples, which is an evidence that the self healing is due to the re-forming of dynamic bonds.
  • Hui Jie Zhang, Tao Lin Sun, Ao Kai Zhang, Yumihiko Ikura, Tasuku Nakajima, Takayuki Nonoyama, Takayuki Kurokawa, Osamu Ito, Hiroyuki Ishitobi, Jian Ping Gong
    ADVANCED MATERIALS 28 (24) 4884 - 4890 0935-9648 2016/06 [Refereed][Not invited]
     
    A series of physical double-network hydrogels is synthesized based on an amphiphilic triblock copolymer. The gel, which contains strong hydrophobic domains and sacrificial dynamic bonds of hydrogen bonds, is stiff and tough, and even stiffens in concentrated saline solution. Furthermore, due to its supramolecular structure, the gel features improved self-healing and self-recovery abilities.
  • Honglei Guo, Takayuki Kurokawa, Masakazu Takahata, Wei Hong, Yoshinori Katsuyama, Feng Luo, Jamil Ahmed, Tasuku Nakajima, Takayuki Nonoyama, Jian Ping Gong
    MACROMOLECULES 49 (8) 3100 - 3108 0024-9297 2016/04 [Refereed][Not invited]
     
    We report, for the first time, the quantitative measurement of the local electric potential of brittle polyelectrolyte hydrogels using the microelectrode technique (MET). Given the solid-like nature of the hydrogels, the difficulty of applying MET is how to make a good contact of the microelectrode to the hydrogel. Poor local contact substantial underestimates the potential. We observed that, the potential measured decays exponentially with the increase of capillary diameter of the microelectrode. This behavior is related to the capillary wall thickness that determines the contact distance of the electrode probe to the hydrogel. The characteristic decay length in respective to the wall thickness is very close to the local Debye length around the capillary. The latter is much larger than that of the bath solution due to the reverse osmosis effect. By using microelectrodes with a tip wall thickness less than the local Debye length, the Donnan potential of polyelectrolyte gel could be accurately measured. Using a micromanipulator, the inserting process of the microelectrode is precisely controlled, and the depth profile of electric potential in the hydrogels can be measured with a spatial resolution down to similar to 5 nm. From the spatial distribution of potential, the microstructure of hydrogels both in bulk and near the surface, the thickness of ultrathin hydrogels, and the heterogeneous layered structure of composite gels, can be determined accurately. The MET established in this work provides a powerful tool for direct characterization of the spatial distribution of electric potential of hydrogels.
  • Kei Mito, Tasuku Nakajima, Takayuki Nonoyama, Jian Ping Gong
    KOBUNSHI RONBUNSHU 公益社団法人 高分子学会 73 (2) 157 - 165 0386-2186 2016 [Refereed][Not invited]
     
    Lipid molecules form anisotropic self-assembled structures such as worm-like micelles or lipid bilayers. Recently the authors have successfully introduced and immobilized uniaxially-oriented lipid bilayers of poly(dodecyl glyceryl itaconate) (PDGI) into the polyacrylamide (PAAm) gel matrix to obtain stable gel-bilayer composites (called PDGI/PAAm gels) with anisotropic structure and functions, such as unidirectional swelling or anisotropic diffusion. One question about this complek is why such a dynamic lipid bilayer structure can be well-stabilized in PAAm gels. In this paper, we focus on the bilayer structure of the PDGI/PAAm gels. In the fast part, the stabilization mechanism of lipid bilayers in the gels, due to hydrogen bonding between PDGI and PAAm, is discussed. In the second part, structure transition and function modification of the PDGI/PAAm gels by insertion of more lipid molecules into bilayers is investigated.
  • Kunpeng Cui, Tao Lin Sun, Takayuki Kurokawa, Tasuku Nakajima, Takayuki Nonoyama, Liang Chen, Jian Ping Gong
    SOFT MATTER 12 (43) 8833 - 8840 1744-683X 2016 [Refereed][Not invited]
     
    Recently, we have developed a series of charge balanced polyampholyte (PA) physical hydrogels by random copolymerization in water, which show extraordinarily high toughness, self-healing ability and viscoelasticity. The excellent performance of PA hydrogels is ascribed to dynamic ionic bond formation through inter-and intra-chain interactions. The randomness results in ionic bonds of wide strength distribution, the strong bonds, which serve as permanent crosslinking, imparting the elasticity, while the weak bonds reversibly break and re-form, dissipating energy. In this work, we developed a simple physical method, called a pre-stretching method, to promote the performance of PA hydrogels. By imposing a pre-stretching on the sample in the as-prepared state, ion complexation during dialysis is prominently accelerated and the final performance is largely promoted. Further analysis suggests that the strong bond formation induced by pre-stretching is responsible for the change in final performance. Pre-stretching decreases the entropy of the system and increases the chain alignment, resulting in an increased possibility for strong bond formation.
  • Riku Takahashi, Yumihiko Ikura, Daniel R. King, Takayuki Nonoyama, Tasuku Nakajima, Takayuki Kurokawa, Hirotoshi Kuroda, Yoshihiro Tonegawa, Jian Ping Gong
    SOFT MATTER 12 (23) 5081 - 5088 1744-683X 2016 [Refereed][Not invited]
     
    Most studies on hydrogel swelling instability have been focused on a constrained boundary condition. In this paper, we studied the mechanical instability of a piece of disc-shaped hydrogel during free swelling. The fast swelling of the gel induces two swelling mismatches; a surface-inner layer mismatch and an annulus-disc mismatch, which lead to the formation of a surface crease pattern and a saddle-like bulk bending, respectively. For the first time, a stripe-like surface crease that is at a right angle on the two surfaces of the gel was observed. This stripe pattern is related to the mechanical coupling of surface instability and bulk bending, which is justified by investigating the swelling-induced surface pattern on thin hydrogel sheets fixed onto a saddle-shaped substrate prior to swelling. A theoretical mechanism based on an energy model was developed to show an anisotropic stripe-like surface crease pattern on a saddle-shaped surface. These results might be helpful to develop novel strategies for controlling crease patterns on soft and wet materials by changing their three-dimensional shape.
  • Takayuki Nonoyama, Jian Ping Gong
    PROCEEDINGS OF THE INSTITUTION OF MECHANICAL ENGINEERS PART H-JOURNAL OF ENGINEERING IN MEDICINE 229 (12) 853 - 863 0954-4119 2015/12 [Refereed][Not invited]
     
    Double-network hydrogels are one of the most promising candidates as artificial soft supporting tissues owing to their excellent mechanical performance, water storage capability, and biocompatibility. A double-network hydrogel consists of two contrasting polymer networks: rigid and brittle first network and soft and ductile second network. To satisfy this double-network requirement, polyelectrolyte and neutral polymer are suitable as the first and the second networks, respectively. Combination of these two networks gives rise to extraordinarily tough double-network hydrogel as a result of substantial internal fracture of the brittle first network at large deformation, which contributes to the energy dissipation. Therefore, the first network serves as the sacrificial bonds to toughen the material. The double-network principle is universal and many kinds of double-network hydrogels composed of various chemical species have been developed. Moreover, a molecular stent technology has been developed to synthesize the double-network hydrogels using neutral polymer network as the brittle first network. The sulfonic double-network hydrogel was found to induce spontaneous hyaline cartilage regeneration in vivo.
  • Chanchal Kumar Roy, Hong Lei Guo, Tao Lin Sun, Abu Bin Ihsan, Takayuki Kurokawa, Masakazu Takahata, Takayuki Nonoyama, Tasuku Nakajima, Jian Ping Gong
    ADVANCED MATERIALS 27 (45) 7344 - + 0935-9648 2015/12 [Refereed][Not invited]
     
    Developing nonspecific, fast, and strong adhesives that can glue hydrogels and biotissues substantially promotes the application of hydrogels as biomaterials. Inspired by the ubiquitous adhesiveness of bacteria, it is reported that neutral polyampholyte hydrogels, through their self-adjustable surface, can show rapid, strong, and reversible adhesion to charged hydrogels and biological tissues through the Coulombic interaction.
  • Daniel R. King, Tao Lin Sun, Yiwan Huang, Takayuki Kurokawa, Takayuki Nonoyama, Alfred J. Crosby, Jian Ping Gong
    MATERIALS HORIZONS 2 (6) 584 - 591 2051-6347 2015/11 [Refereed][Not invited]
     
    Ligaments are unique wet biological tissues with high tensile modulus and fracture stress, combined with high bending flexibility. Developing synthetic materials with these properties is a significant challenge. Hydrogel composites made from high stiffness fabrics is a strategy to develop such unique materials; however, the ability to produce these materials has proven difficult, since common hydrogels swell in water and interact poorly with solid components, limiting the transfer of force from the fabric to the hydrogel matrix. In this work, for the first time, we successfully produce extraordinarily tough hydrogel composites by strategically selecting a recently developed tough hydrogel that de-swells in water. The new composites, consisting of polyampholyte hydrogels and glass fiber woven fabrics, exhibit extremely high effective toughness (250 000 J m(-2)), high tear strength (similar to 65 N mm(-1)), high tensile modulus (606 MPa), and low bending modulus (4.7 MPa). Even though these composites are composed of water-containing, biocompatible materials, their mechanical properties are comparable to high toughness Kevlar/polyurethane blends and fiber-reinforced polymers. Importantly, the mechanical properties of these composites greatly outperform the properties of either individual component. A mechanism is proposed based on established fabric tearing theory, which will enable the development of a new generation of mechanically robust composites based on fabrics. These results will be important towards developing soft biological prosthetics, and more generally for commercial applications such as tear-resistant gloves and bulletproof vests.
  • Koshiro Sato, Tasuku Nakajima, Toshiyuki Hisamatsu, Takayuki Nonoyama, Takayuki Kurokawa, Jian Ping Gong
    ADVANCED MATERIALS 27 (43) 6990 - + 0935-9648 2015/11 [Refereed][Not invited]
     
    Novel, tough, strong, and self-healable polyacrylamide (PAAm) gels are fabricated by inducing an appropriate phase-separation structure using a poor solvent. The phase separation induces a gel-glass-like transition of the PAAm gels, providing the gels an anomalously high modulus (211 MPa), fracture stress (7.13 MPa), and fracture energy (4.16 x 10(4) J m(-2)), while keeping a high solvent content (approximate to 60 vol%).
  • 和田 進, 北村 信人, 野々山 貴行, 木山 竜二, 仙葉 愼吾, 比嘉 浩太郎, 黒川 孝幸, Gong Jian Ping, 安田 和則
    日本整形外科学会雑誌 (公社)日本整形外科学会 89 (8) S1585 - S1585 0021-5325 2015/09
  • Jamil Ahmed, Tetsurou Yamamoto, Honglei Guo, Takayuki Kurokawa, Takayuki Nonoyama, Tasuku Nakajima, Jian Ping Gong
    MACROMOLECULES 48 (15) 5394 - 5401 0024-9297 2015/08 [Refereed][Not invited]
     
    A simplified model describing the sliding friction of hydrogel on solid surface by dynamic adsorption of the polymer chains is proposed on the basis of polymer adsorption-repulsion theory. This dynamic adsorption model is used to analyze the friction results of zwitterionic hydrogels sliding over glass substrates with different substrate wettability, hydrogel swelling degree, ionic strength, and pH of bath solution. The adsorption time tau(b) of polymer strands is found to decrease with the increase in sliding velocity or the Weissenberg number as a result of stretching. The adsorption time tau(0)(b), and the adsorption energy U-ads at stress-free condition, which are characteristic for each friction system, are also estimated. Roughly, a master curve is observed for the normalized adsorption lifetime tau(b)/tau(0)(b) and the Weissenberg number, with less dependence on the adsorption energy and the bulk properties of the gels in the observed experimental conditions. Thus, the dynamic adsorption model successfully correlates the frictional behavior of hydrogels with the adsorption dynamics of polymer strands, which gives insight into the molecular design of hydrogels with predefined frictional properties for biomedical applications.
  • Md. Tariful Islam Mredha, Xi Zhang, Takayuki Nonoyama, Tasuku Nakajima, Takayuki Kurokawa, Yasuaki Takagid, Jian Ping Gong
    JOURNAL OF MATERIALS CHEMISTRY B 3 (39) 7658 - 7666 2050-750X 2015 [Refereed][Not invited]
     
    Marine collagen has been attracting attention as a medical material in recent times due to the low risk of pathogen infection compared to animal collagen. Type I collagen extracted from the swim bladder of Bester sturgeon fish has excellent characteristics such as high denaturation temperature, high solubility, low viscosity and an extremely fast rate to form large bundle of fibers under certain conditions. These specific characteristics of swim bladder collagen (SBC) permit us to create stable, disk shaped hydrogels with concentric orientation of collagen fibers by the controlled diffusion of neutral buffer through collagen solution at room temperature. However, traditionally used animal collagens, e.g. calf skin collagen (CSC) and porcine skin collagen (PSC), could not form any stable and oriented structure by this method. The mechanism of the superstructure formation of SBC by a diffusion induced gelation process has been explored. The fast fibrillogenesis rate of SBC causes a quick squeezing out of the solvent from the gel phase to the sol phase during gelation, which builds an internal stress at the gel-sol interface. The tensile stress induces the collagen molecules of the gel phase to align along the gel-sol interface direction to give this concentric ring-shaped orientation pattern. On the other hand, the slow fibrillogenesis rate of animal collagens due to the high viscosity of the solution does not favor the ordered structure formation. The denaturation temperature of SBC increases significantly from 31 degrees C to 43 degrees C after gelation, whereas that of CSC and PSC were found to increase a little. Rheology experiment shows that the SBC gel has storage modulus larger than 15 kPa. The SBC hydrogels with thermal and mechanical stability have potential as bio-materials for tissue engineering applications.
  • Riku Takahashi, Zi Liang Wu, Md Arifuzzaman, Takayuki Nonoyama, Tasuku Nakajima, Takayuki Kurokawa, Jian Ping Gong
    NATURE COMMUNICATIONS 5 4490  2041-1723 2014/08 [Refereed][Not invited]
     
    Biomacromolecules usually form complex superstructures in natural biotissues, such as different alignments of collagen fibres in articular cartilages, for multifunctionalities. Inspired by nature, there are efforts towards developing multiscale ordered structures in hydrogels (recognized as one of the best candidates of soft biotissues). However, creating complex superstructures in gels are hardly realized because of the absence of effective approaches to control the localized molecular orientation. Here we introduce a method to create various superstructures of rigid polyanions in polycationic hydrogels. The control of localized orientation of rigid molecules, which are sensitive to the internal stress field of the gel, is achieved by tuning the swelling mismatch between masked and unmasked regions of the photolithographic patterned gel. Furthermore, we develop a double network structure to toughen the hydrogels with programmed superstructures, which deform reversibly under large strain. This work presents a promising pathway to develop superstructures in hydrogels and should shed light on designing biomimetic materials with intricate molecular alignments.
  • Youfeng Yue, Takayuki Kurokawa, Md Anamul Haque, Tasuku Nakajima, Takayuki Nonoyama, Xufeng Li, Itsuro Kajiwara, Jian Ping Gong
    NATURE COMMUNICATIONS 5 4659  2041-1723 2014/08 [Refereed][Not invited]
     
    Photonic crystals with tunability in the visible region are of great interest for controlling light diffraction. Mechanochromic photonic materials are periodically structured soft materials designed with a photonic stop-band that can be tuned by mechanical forces to reflect specific colours. Soft photonic materials with broad colour tunability and fast colour switching are invaluable for application. Here we report a novel mechano-actuated, soft photonic hydrogel that has an ultrafast-response time, full-colour tunable range, high spatial resolution and can be actuated by a very small compressive stress. In addition, the material has excellent mechanical stability and the colour can be reversibly switched at high frequency more than 10,000 times without degradation. This material can be used in optical devices, such as full-colour display and sensors to visualize the time evolution of complicated stress/strain fields, for example, generated during the motion of biological cells.
  • Haiyan Yin, Taigo Akasaki, Tao Lin Sun, Tasuku Nakajima, Takayuki Kurokawa, Takayuki Nonoyama, Toshio Taira, Yoshiyuki Saruwatari, Jian Ping Gong
    JOURNAL OF MATERIALS CHEMISTRY B 1 (30) 3685 - 3693 2050-750X 2013 [Refereed][Not invited]
     
    Polyzwitterionic materials, which have both cationic and anionic groups in the polymeric repeat unit, show excellent anti-biofouling properties and are drawing more attention in the biomedical field. In this study, we have successfully synthesized novel single network hydrogels and double network (DN) hydrogels from the zwitterionic monomer, N-(carboxymethyl)-N,N-dimethyl-2-(methacryloyloxy) ethanaminium, inner salt (CDME). The polyCDME (PCDME) single network hydrogel behaves like a hydrophilic neutral hydrogel and its properties are not sensitive to temperature, pH, or ionic strength over a wide range. DN hydrogels using the poly(2-acrylamido-2-methylpropanesulfonic) (PAMPS) as the first network and PCDME as the second network, having a Young's modulus of 0.2-0.9 MPa, possess excellent mechanical strength (fracture stress: 1.2-1.4 MPa, fracture strain: 2.2-6.0 mm/mm) and toughness (work of extension at fracture: 0.9-2.4 MJ m(-3)) depending on the composition ratio of PCDME to PAMPS. The strength and toughness of the optimized PAMPS/PCDME DN is comparable to the normal PAMPS/PAAm DN hydrogels that use poly(acrylamide) (PAAm) as the second network. By macrophage adhesion test, both the PCDME hydrogels and the PAMPS/PCDME DN hydrogels have shown excellent anti-biofouling properties. These results demonstrate that the PCDME-based DN hydrogels have high potential as a novel soft and wet biomaterial.
  • Takayuki Nonoyama, Takatoshi Kinoshita, Masahiro Higuchi, Kenji Nagata, Masayoshi Tanaka, Mari Kamada, Kimiyasu Sato, Katsuya Kato
    APPLIED SURFACE SCIENCE 262 8 - 12 0169-4332 2012/12 [Refereed][Not invited]
     
    We demonstrate arrangement techniques of proteins and cells using an amorphous calcium phosphate (ACP) nanofiber scaffold. It is well known that protein andosteoblastic cell are preferably adsorbed onto ACP surface. The ACP nanofiber scaffold was prepared by calcium phosphate mineralization on a polypeptide monolayer-coated mica substrate, and ACP nanofibers were oriented unidirectionaly. In a protein system, the ACP nanofiber scaffold was soaked in a fluorescein isothiocyanate conjugated immunoglobulin G (IgG-FITC) aqueous solution. From fluorescence microscopic measurement, the adsorbed IgG-FITC was highly confined and arranged on the ACP nanofiber. In a cell system, a mouse osteoblast-like cell (MC3T3-E1) behavior on the ACP nanofiber scaffold was observed. The cell was elongated unidirectionaly, and its cytoskeletal shape showed high aspect ratio. These results are clearly different from an ACP bulk template or bare mica substrate, and the arrangement technique enable to fabricate a fine-tuned biomaterial template. Crown Copyright (c) 2011 Published by Elsevier B.V. All rights reserved.
  • Tatsuya Kuno, Takayuki Nonoyama, Kiyoshi Hirao, Katsuya Kato
    CHEMISTRY LETTERS 41 (11) 1547 - 1549 0366-7022 2012/11 [Refereed][Not invited]
     
    To investigate the influence of the secondary structure of peptide on silica biomineralization, alpha-helix and beta-sheet conformational peptides were synthesized and applied as catalyst in silica biomineralization.
  • Takayuki Nonoyama, Takatoshi Kinoshita, Masahiro Higuchi, Kenji Nagata, Masayoshi Tanaka, Kimiyasu Sato, Katsuya Kato
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 134 (21) 8841 - 8847 0002-7863 2012/05 [Refereed][Not invited]
     
    Hydroxyapatite is mineralized along the long axis of collagen fiber during osteogenesis. Mimicking such biomineralization has great potential to control inorganic structures and is fast becoming an important next-generation inorganic synthesis method. Inorganic matter synthesized by biomineralization can have beautiful and functional structures that cannot be created artificially. In this study, we applied biomineralization to the synthesis of the only photocatalyst in practical use today, titanium dioxide (TiO2). The photocatalytic activity of TiO2 mainly relates to three properties: morphology, crystal phase, and light-use efficiency. To optimize TiO2 morphology, we used a simple sequential peptide as an organic template. TiO2 mineralized by a beta-sheet peptide nanofiber template forms fiber-like shapes that are not observed for mineralization by peptides in the shape of random coils. To optimize TiO2 crystal phase, we mineralized TiO2 with the template at 400 degrees C to transform it into the rutile phase and at 700 degrees C to transform it into a mixed phase of anatase and rutile. To optimize light-use efficiency, we introduced nitrogen atoms of the peptide into the TiO2 structure as doped elemental material during sintering. Thus, this biomineralization method enables control of inorganic morphology, crystal phase, and light-use efficiency in a single process.
  • Kazuki Murai, Takayuki Nonoyama, Takao Saito, Katsuya Kato
    CATALYSIS SCIENCE & TECHNOLOGY 2 (2) 310 - 315 2044-4753 2012 [Refereed][Not invited]
     
    The enzyme subtilisin from Bacillus licheniformis (4.1 nm x 7.8 nm x 3.7 nm) was easily immobilized onto a mesoporous silica (MPS) surface by a direct one-step method and the amount of subtilisin immobilized on each functionalized MPS surface was similar (approximately 0.30 mg of enzyme/ mg of MPS support). The catalytic performance (hydrolytic activity and enantioselectivity) of the immobilized subtilisin was found to depend on the properties of the organofunctional group on the MPS surface. In particular, the hydrolytic activity of enzyme immobilized on ethyl-group-modified MPS increased relative to the behavior of free subtilisin (relative activity 143%). The activity of subtilisin immobilized on the modified MPS was improved by facilitation of contact between enzyme and hydrophobic substrate by increase in hydrophobicity with an immobilized carrier. On the other hand, the enantioselectivity of subtilisin immobilized on 3-mercaptopropyl-group-modified MPS significantly decreased (enantioselectivity of 2.6 compared to 4.3 for free subtilisin). This decrease in enantioselectivity indicated that the mercapto group on the MPS surface was changed in the secondary structure of enzyme by interacting between enzyme and immobilized support. The denaturation temperature of subtilisin immobilized on no-substituted MPS increased (65 degrees C compared with 57 degrees C for free subtilisin). The denaturation temperature of immobilized subtilisin was dependent on the absorbed fraction of thermal energy by functional groups on the MPS surface.
  • Takayuki Nonoyama, Hokuto Ogasawara, Masayoshi Tanaka, Masahiro Higuchi, Takatoshi Kinoshita
    SOFT MATTER 8 (45) 11531 - 11536 1744-683X 2012 [Refereed][Not invited]
     
    We performed amorphous calcium phosphate (ACP) and hydroxyapatite (HAp) mineralization in peptide hydrogels for the formation of a novel bone-filling material. We prepared two kinds of beta-sheet peptides, (LE)(8) and (VEVSVKVS)(2), respectively, using hydrophilic glutamic acid (E), serine (S) and lysine (K), and hydrophobic leucine (L) and valine (V). Both peptides hierarchically self-assembled as nanofibers and formed hydrogels in the presence of calcium ions. The formation of the hydrogel was due to the ionic cross-linkage between carboxyl groups in the glutamic acid side chains of the peptide nanofibers and the calcium ion. (LE)(8) formed a clear hydrogel above a calcium ion concentration of 4.0 x 10(-3) M and the hydrogel collapsed at 1.0 x 10(-2) M, owing to excess ionic cross-linkage. On the other hand, (VEVSVKVS)(2) containing two glutamic acid residues per molecule retained the hydrogel structure at a higher concentration of calcium ions in the hydrogel where the (LE)(8) hydrogel collapsed. The viscoelastic property of both peptide hydrogels was increased by increasing the calcium ion concentration, showing adequate strength as a bone-filling material. When phosphate ion was added into the (LE)(8) hydrogel containing calcium ion, ACP was mineralized along the peptide nanofiber in the hydrogel under neutral pH. The (VEVSVKVS)(2) hydrogel, on the other hand, produced HAp under basic pH. In addition, the peptide hydrogel smoothly recovered its original moduli just after the shear deformation of the hydrogel. It was also clarified that calcium ions are not only a source of mineralization but also induce an increase in the mechanical strength of the hydrogels as a reinforcing agent. It was shown, moreover, that the crystallinity of the HAp was slightly dependent on the modulus of the peptide hydrogels. Therefore, it may be said that peptide hydrogels are applicable for tailor-made injectable bone-filling materials.
  • Tatsuya Kuno, Takayuki Nonoyama, Kiyoshi Hirao, Katsuya Kato
    LANGMUIR 27 (21) 13154 - 13158 0743-7463 2011/11 [Refereed][Not invited]
     
    The catalytic effect of various sequential peptides for silica biomineralization has been studied. In peptide sequence design, lysine (K) and histidine (H) were selected as the standard amino acids and aspartic acid (D) was selected to promote the charge relay effects, such as in the enzyme active site. Therefore, homopolypeptides (K(10) and H(10)), block poly-peptides (K(5)D(5) and H(5)D(5)), and alternate polypeptides [(KD)(5) and (HD)(5)] were designed, and the dehydration reaction ability of trimethylethoxysilane was investigated as a quantitative model of silica mineralization. The catalytic activity per basic residue of alternate polypeptide was the highest because of the charge relay effects at the surface of the peptide. In silica mineralization using tetraethoxysilane, spherical silica particles were obtained, and their size is related to the catalytic activities of the peptides in the model systems. From these results, the effect of the functional group combination by the peptide sequence design enables the control of the efficiency of mineralization and preparation of specific inorganic materials.
  • Takayuki Nonoyama, Masayoshi Tanaka, Yoshihito Inai, Masahiro Higuchi, Takatoshi Kinoshita
    ACS NANO 5 (8) 6174 - 6183 1936-0851 2011/08 [Refereed][Not invited]
     
    We have demonstrated a unique method for rational arrangement of gold (Au) nanoparticles on a beta-sheet peptide template through nucleobase pairing. For the template, the 16-mer peptide 1 was synthesized, which is based on an alternating amphiphilic sequence of Asp-Leu. Here Leu at the sixth position Is replaced by thymine-modified Lys, and a polyethylene glycol chain is introduced to the C-terminus. The surface of Au nanoparticles was modified with, the complementary adenyl group. Peptide 1 formed a stable beta-sheet monolayer at the air/water interface Under an appropriate surface pressure. The monolayer film transferred onto a mica surface by the Langmuir-Blodgett method showed a linearly striped pattern with 6.1 nm average stripe width and 6 nm average interval between stripes, derived from beta-sheet assembly. The adenine-bound Au nanoparticles were successfully Immobilized on the thymine-bound template through a complementary adenine-thymine hydrogen bonding pair. Interestingly; linear, assembly. mixtures of. the Au nanoparticles were observed, thus being successfully reproduced by the original striped pattern of the template of 1. Our method might readily fabricate Au materials with our desirable 2D pattern through fine-tuning of beta-sheet sequence and nucleobase position.
  • Takayuki Nonoyama, Takatoshi Kinoshita, Masahiro Higuchi, Kenji Nagata, Masayoshi Tanaka, Kimiyasu Sato, Katsuya Kato
    LANGMUIR 27 (11) 7077 - 7083 0743-7463 2011/06 [Refereed][Not invited]
     
    We studied the effect of surface-functional-group position on precipitate morphology in the earliest stage of calcium phosphate biomineralization and determined the detailed mechanism of precipitation starting from nucleation to precipitate growth. The biomineralization template was a beta-sheet peptide scaffold prepared by adsorption with carboxyl groups arranged at strict 7 angstrom intervals. Phosphate was then introduced. Within 10 s, highly ordered embryos of calcium phosphate were formed and confined by a peptide nanofiber pattern. They repeatedly nucleated and dissolved, with the larger embryos absorbing the smaller ones in a clear demonstration of an Ostwald-ripening-like phenomenon, then aggregated in a line pattern, and finally formed highly ordered nanofibers of amorphous calcium phosphate. This multistep growth process constitutes the earliest stage of biomineralization.
  • Takayuki Nonoyama, Masayoshi Tanaka, Takatoshi Kinoshita, Fukue Nagata, Kimiyasu Sato, Katsuya Kato
    CHEMICAL COMMUNICATIONS 46 (37) 6983 - 6985 1359-7345 2010/10 [Refereed][Not invited]
     
    To investigate the influence of the spatial placement of the organic functional groups in mineralization, an amphiphilic peptide assembled monolayer with strictly arrayed carboxyl groups was applied to a mineralization system of calcium phosphate.

Books etc

Conference Activities & Talks

  • 田中香月, 野々山貴行, 深尾一城, 木山竜二, GONG Jian Ping
    高分子ゲル研究討論会講演要旨集  2019/01
  • 鈴木裕貴, 野々山貴行, 野々山貴行, WANG Lei, WANG Lei, 津田真寿美, 津田真寿美, 木山竜二, 安田和則, 安田和則, GONG Jian Ping, GONG Jian Ping
    高分子ゲル研究討論会講演要旨集  2019/01
  • 金佑泳, 小野寺智洋, 近藤英司, 野々山貴行, 馬場力哉, 上徳善太, 宝満健太郎, 菱村亮介, 岩崎倫政
    整形外科バイオマテリアル研究会プログラム・抄録集  2018/11
  • 藤岡慶伍, 野々山貴行, 野々山貴行, GUO Honglei, GUO Honglei, GUO Hui, GUO Hui, 中島祐, 中島祐, 黒川孝幸, 黒川孝幸, GONG Jian Ping, GONG Jian Ping
    高分子学会予稿集(CD-ROM)  2018/08
  • 木山竜二, 野々山貴行, 野々山貴行, 中島祐, 中島祐, 黒川孝幸, 黒川孝幸, GONG Jian Ping, GONG Jian Ping
    高分子学会予稿集(CD-ROM)  2018/08
  • 野々山貴行, 野々山貴行, LEE Yong Woo, 太田玖美, 藤岡慶伍, GONG Jian Ping, GONG Jian Ping
    高分子学会予稿集(CD-ROM)  2018/08
  • 高橋由葵子, 松田昂大, 中島祐, 中島祐, 印出井努, 印出井努, 野々山貴行, 野々山貴行, 黒川孝幸, 黒川孝幸, GONG Jian Ping, GONG Jian Ping
    高分子学会予稿集(CD-ROM)  2018/08
  • 鈴木裕貴, 野々山貴行, 野々山貴行, WANG Lei, WANG Lei, 津田真寿美, 津田真寿美, 木山竜二, 安田和則, 安田和則, GONG Jian Ping, GONG Jian Ping
    高分子学会予稿集(CD-ROM)  2018/08
  • 奥村剛士, 高橋陸, KING Daniel R, KING Daniel R, 中島祐, 中島祐, 野々山貴行, 野々山貴行, 黒川孝幸, 黒川孝幸, GONG Jian Ping, GONG Jian Ping
    高分子学会予稿集(CD-ROM)  2018/08
  • 野々山貴行
    高分子学会予稿集(CD-ROM)  2018/08
  • 深尾一城, 野々山貴行, 中島祐, 黒川孝幸, 河井貴彦, GONG Jian Ping
    高分子学会予稿集(CD-ROM)  2018/08
  • 難波遼, 松田昂大, 中島祐, 中島祐, 野々山貴行, 野々山貴行, 黒川孝幸, 黒川孝幸, GONG Jian Ping, GONG Jian Ping
    高分子学会予稿集(CD-ROM)  2018/08
  • 奥村剛士, 高橋陸, KING Daniel R, KING Daniel R, 中島祐, 中島祐, 野々山貴行, 野々山貴行, 黒川孝幸, 黒川孝幸, GONG Jian Ping, GONG Jian Ping
    高分子学会予稿集(CD-ROM)  2018/05
  • 深尾一城, 野々山貴行, 野々山貴行, 中島祐, 中島祐, 黒川孝幸, 黒川孝幸, GONG Jian Ping, GONG Jian Ping
    高分子学会予稿集(CD-ROM)  2018/05
  • 木山竜二, 野々山貴行, 中島祐, 黒川孝幸, GONG Jian Ping
    日本セラミックス協会年会講演予稿集(CD-ROM)  2018/03
  • 深尾一城, 野々山貴行, 古澤和也, 黒川孝幸, 中島祐, GONG Jian Ping
    日本セラミックス協会年会講演予稿集(CD-ROM)  2018/03
  • 奥村剛士, 高橋陸, 黒川孝幸, 黒川孝幸, KING Daniel R, KING Daniel R, 中島祐, 中島祐, 孫桃林, 孫桃林, 野々山貴行, 野々山貴行, きょう剣萍, きょう剣萍
    高分子学会北海道支部研究発表会講演要旨集  2018/01
  • 田中香月, 野々山貴行, 野々山貴行, 木山竜二, 深尾一城, 黒川孝幸, 黒川孝幸, きょう剣萍, きょう剣萍
    高分子学会北海道支部研究発表会講演要旨集  2018/01
  • 難波遼, 松田昂大, 中島祐, 中島祐, 野々山貴行, 野々山貴行, 黒川孝幸, 黒川孝幸, きょう剣萍, きょう剣萍
    高分子学会北海道支部研究発表会講演要旨集  2018/01
  • 李永祐, 野々山貴行, 野々山貴行, 中島祐, 中島祐, 黒川孝幸, 黒川孝幸, きょう剣萍, きょう剣萍
    高分子学会北海道支部研究発表会講演要旨集  2018/01
  • 井上あかね, MD.ANAMUL Haque, 黒川孝幸, 黒川孝幸, 中島祐, 中島祐, 野々山貴行, 野々山貴行, きょう剣萍, きょう剣萍
    高分子学会北海道支部研究発表会講演要旨集  2018/01
  • 野々山貴行, 野々山貴行, 太田玖美, LEE Yong Woo, 藤岡慶伍, 黒川孝幸, 黒川孝幸, GONG Jian Ping, GONG Jian Ping
    高分子ゲル研究討論会講演要旨集  2018/01
  • 木山竜二, 野々山貴行, 野々山貴行, 中島祐, 中島祐, 黒川孝幸, 黒川孝幸, GONG Jian Ping, GONG Jian Ping
    高分子ゲル研究討論会講演要旨集  2018/01
  • 猪飼拓真, 高橋陸, キング ダニエル, キング ダニエル, 中島祐, 中島祐, 野々山貴行, 野々山貴行, 黒川孝幸, 黒川孝幸, グン剣萍, グン剣萍
    化学系学協会北海道支部冬季研究発表会(Web)  2018
  • 黒川孝幸, 野々山貴行, 中島祐, GONG J. P, 小池智, 平井悠司, 大園拓哉
    レオロジー討論会講演要旨集  2017/10
  • 難波遼, 松田昂大, 中島祐, 中島祐, 野々山貴行, 野々山貴行, 黒川孝幸, 黒川孝幸, GONG Jian Ping, GONG Jian Ping
    高分子学会予稿集(CD-ROM)  2017/09
  • 奥村剛士, 高橋陸, KING Daniel R, KING Daniel R, 中島祐, 中島祐, SUN Taolin, SUN Taolin, 野々山貴行, 野々山貴行, 黒川孝幸, 黒川孝幸, GONG Jian Ping, GONG Jian Ping
    高分子学会予稿集(CD-ROM)  2017/09
  • 村井一喜, 楜澤和也, 大塚渓斗, 野々山貴行, 松本睦良
    高分子学会予稿集(CD-ROM)  2017/09
  • 井上あかね, ANAMUL Haque Md, 黒川孝幸, 黒川孝幸, 中島祐, 中島祐, 野々山貴行, 野々山貴行, GONG Jian Ping, GONG Jian Ping
    高分子学会予稿集(CD-ROM)  2017/09
  • 村川航平, SUN Taolin, SUN Taolin, KING Daniel R, KING Daniel R, 野々山貴行, 野々山貴行, 中島祐, 中島祐, 黒川孝幸, 黒川孝幸, GONG Jian Ping, GONG Jian Ping
    高分子学会予稿集(CD-ROM)  2017/09
  • KIM W.Y, 近藤英司, 小野寺智洋, 野々山貴行, 馬場力哉, 本谷和俊, 上徳善太, 松原新史, 宝満健太郎, 菱村亮介, TERKAWI Muhamad, 岩崎倫政
    日本整形外科学会雑誌  2017/08
  • 奥村剛士, 高橋陸, KING Daniel R, KING Daniel R, 中島祐, 中島祐, SUN Taolin, SUN Taolin, 野々山貴行, 野々山貴行, 黒川孝幸, 黒川孝幸, GONG Jian Ping, GONG Jian Ping
    高分子学会予稿集(CD-ROM)  2017/05
  • 高橋陸, DANIEL King, DANIEL King, 孫桃林, 孫桃林, 野々山貴行, 野々山貴行, 中島祐, 中島祐, 黒川孝幸, 黒川孝幸, GONG Jian Ping, GONG Jian Ping
    高分子学会予稿集(CD-ROM)  2017/05
  • 野々山貴行, 野々山貴行, 太田玖美, LEE Yong Woo, 中島祐, 中島祐, 黒川孝幸, 黒川孝幸, GONG Jian Ping, GONG Jian Ping
    高分子学会予稿集(CD-ROM)  2017/05
  • 中島祐, 中島祐, MREDHA Md.Tariful Islam, 黒川孝幸, 黒川孝幸, 野々山貴行, 野々山貴行, GONG Jian Ping, GONG Jian Ping
    高分子学会予稿集(CD-ROM)  2017/05
  • 村井一喜, 楜澤和也, 大塚渓斗, 野々山貴行, 松本睦良
    高分子学会予稿集(CD-ROM)  2017/05
  • LEE Yong Woo, 野々山貴行, 野々山貴行, 中島祐, 中島祐, 黒川孝幸, 黒川孝幸, GONG Jian Ping, GONG Jian Ping
    高分子学会予稿集(CD-ROM)  2017/05
  • 福田泰紀, 黒川孝幸, 黒川孝幸, KING Daniel R, KING Daniel R, 中島祐, 中島祐, 野々山貴行, 野々山貴行, SUN Taolin, SUN Taolin, GONG Jian Ping, GONG Jian Ping
    高分子ゲル研究討論会講演要旨集  2017/01
  • 村川航平, SUN Taolin, SUN Taolin, KING Daniel R, KING Daniel R, 野々山貴行, 野々山貴行, 中島祐, 中島祐, 黒川孝幸, 黒川孝幸, GONG Jian Ping, GONG Jian Ping
    高分子ゲル研究討論会講演要旨集  2017/01
  • 難波遼, 松田昂大, 中島祐, 中島祐, 野々山貴行, 野々山貴行, 黒川孝幸, 黒川孝幸, GONG Jian Ping, GONG Jian Ping
    高分子ゲル研究討論会講演要旨集  2017/01
  • 難波遼, 松田昂大, 中島祐, 中島祐, 野々山貴行, 野々山貴行, 黒川孝幸, 黒川孝幸, きょう剣萍, きょう剣萍
    高分子学会北海道支部研究発表会講演要旨集  2017
  • 水戸京, 李旭峰, HAQUE Md. Anamul, 黒川孝幸, 黒川孝幸, 中島祐, 中島祐, 野々山貴行, 野々山貴行, きょう剣萍, きょう剣萍
    高分子学会北海道支部研究発表会講演要旨集  2017
  • 奥村剛士, 高橋陸, 黒川孝幸, 黒川孝幸, KING Daniel R, KING Daniel R, 中島祐, 中島祐, 孫桃林, 孫桃林, 野々山貴行, 野々山貴行, きょう剣萍, きょう剣萍
    高分子学会北海道支部研究発表会講演要旨集  2017
  • 猪飼拓真, 高橋陸, キング ダニエル, キング ダニエル, 中島祐, 中島祐, 野々山貴行, 野々山貴行, 黒川孝幸, 黒川孝幸, きょう剣萍, きょう剣萍
    高分子学会北海道支部研究発表会講演要旨集  2017
  • 村川航平, 孫桃林, 孫桃林, KING ダニエル R, KING ダニエル R, 野々山貴行, 野々山貴行, 中島祐, 中島祐, 黒川孝幸, 黒川孝幸, きょう剣萍, きょう剣萍
    高分子学会北海道支部研究発表会講演要旨集  2017
  • 尾崎雄平, 中島祐, 中島祐, 野々山貴行, 野々山貴行, 黒川孝幸, 黒川孝幸, きょう剣萍, きょう剣萍
    高分子学会北海道支部研究発表会講演要旨集  2017
  • 深尾一城, 野々山貴行, 野々山貴行, 古澤和也, 古澤和也, 黒川孝幸, 黒川孝幸, 中島祐, 中島祐, きょう剣萍, きょう剣萍
    高分子学会北海道支部研究発表会講演要旨集  2017
  • 福田泰紀, 黒川孝幸, 黒川孝幸, キング ダニエル, キング ダニエル, 中島祐, 中島祐, 野々山貴行, 野々山貴行, 孫桃林, 孫桃林, きょう剣萍, きょう剣萍
    高分子学会北海道支部研究発表会講演要旨集  2017
  • 太田玖美, 野々山貴行, 野々山貴行, 中島祐, 中島祐, 黒川孝幸, 黒川孝幸, きょう剣萍, きょう剣萍
    高分子学会北海道支部研究発表会講演要旨集  2017
  • 田中香月, 野々山貴行, 野々山貴行, 中島祐, 中島祐, 黒川孝幸, 黒川孝幸, きょう剣萍, きょう剣萍
    高分子学会北海道支部研究発表会講演要旨集  2017
  • 深尾一城, 野々山貴行, 野々山貴行, 黒川孝幸, 黒川孝幸, 中島祐, 中島祐, きょう剣萍, きょう剣萍
    日本バイオマテリアル学会シンポジウム予稿集  2016/11
  • 野々山貴行, 和田進, 木山竜二, 北村信人, 北村信人, 安田和則, きょう剣萍, きょう剣萍
    日本バイオマテリアル学会シンポジウム予稿集  2016/11
  • 和田進, 北村信人, 野々山貴行, 木山竜二, 仙葉愼吾, 小野寺純, 横田正司, 後藤佳子, 比嘉浩太郎, 黒川孝幸, PING Gong Jian, 安田和則
    日本整形外科学会雑誌  2016/08
  • 比嘉浩太郎, 北村信人, 後藤佳子, 黒川孝幸, 和田進, 野々山貴行, PING Gong Jian, 金谷文則, 安田和則
    日本整形外科学会雑誌  2016/08
  • 深尾一城, 野々山貴行, 黒川孝幸, 中島祐, GONG Jian Ping
    日本セラミックス協会秋季シンポジウム講演予稿集(CD-ROM)  2016/08
  • 木山竜二, 野々山貴行, 中島祐, 黒川孝幸, GONG JianPing
    日本セラミックス協会秋季シンポジウム講演予稿集(CD-ROM)  2016/08
  • 野々山貴行, 野々山貴行, 和田進, 木山竜二, 北村信人, 北村信人, 黒川孝幸, 黒川孝幸, 中島祐, 中島祐, 安田和則, GONG Jian Ping, GONG Jian Ping
    高分子学会予稿集(CD-ROM)  2016/08
  • 高橋陸, DANIEL King, DANIEL King, 野々山貴行, 野々山貴行, 中島祐, 中島祐, 黒川孝幸, 黒川孝幸, GONG Jian Ping, GONG Jian Ping
    高分子学会予稿集(CD-ROM)  2016/08
  • 猪飼拓真, 高橋陸, KING Daniel R, 中島祐, 野々山貴行, 黒川孝幸, GONG Jian Ping
    高分子学会予稿集(CD-ROM)  2016/08
  • 大塚渓斗, 村井一喜, 野々山貴行, 松本睦良
    高分子学会予稿集(CD-ROM)  2016/08
  • 尾崎雄平, 中島祐, 中島祐, 野々山貴行, 野々山貴行, 黒川孝幸, 黒川孝幸, CONG Jian Ping, CONG Jian Ping
    高分子学会予稿集(CD-ROM)  2016/08
  • MREDHA Md. Tariful Islam, ZHANG Xi, NONOYAMA Takayuki, NAKAJIMA Tasuku, KUROKAWA Takayuki, HAQUE Md. Anamul, TAKAGI Yasuaki, GONG Jian Ping
    高分子ゲル研究討論会講演要旨集  2016/01
  • 猪飼拓真, 高橋陸, 中島祐, 野々山貴行, 黒川孝幸, GONG Jian Ping
    高分子ゲル研究討論会講演要旨集  2016/01
  • 福田泰紀, 黒川孝幸, 中島祐, 野々山貴行, GONG Jian Ping
    高分子ゲル研究討論会講演要旨集  2016/01
  • KAROBI Sadia Nazneen, SUN Tao Lin, KUROKAWA Takayuki, LUO Feng, NAKAJIMA Tasuku, NONOYAMA Takayuki, GONG Jian Ping
    レオロジー討論会講演要旨集  2015/09
  • 和田進, 北村信人, 野々山貴行, 木山竜二, 仙葉愼吾, 比嘉浩太郎, 黒川孝幸, GONG Jian Ping, 安田和則
    日本整形外科学会雑誌  2015/09
  • ZHANG Huijie, SUN Tao Lin, IKURA Yumihiko, ZHANG Aokai, LI Xufeng, NAKAJIMA Tasuku, NONOYAMA Takayuki, KURUKAWA Takayuki, ITO Osamu, ISHITOBI Hiroyuki, GONG Jian Ping
    高分子学会予稿集(CD-ROM)  2015/08
  • ZHANG Aokai, NAKAJIMA Tasuku, KUROKAWA Takayuki, NONOYAMA Takayuki, GONG Jian Ping
    高分子学会予稿集(CD-ROM)  2015/08
  • GUO Honglei, KUROKAWA Takayuki, TAKAHATA Masakazu, KATSUYAMA Yoshinori, LUO Feng, AHMED Jamil, NAKAJIMA Tasuku, NONOYAMA Takayuki, GONG JianPing
    高分子学会予稿集(CD-ROM)  2015/08
  • ROY Chanchal Kumar, GUO Hong Lei, IHSAN Abu Bin, SUN Tao Lin, NONOYAMA Takayuki, NAKAJIMA Tasuku, KUROKAWA Takayuki, GONG Jian Ping
    高分子学会予稿集(CD-ROM)  2015/08
  • Diffusion induced superstructure formation in swim bladder collagen  [Not invited]
    MREDHA MD. TARIFUL ISLAM, ZHANG XI, NONOYAMA TAKAYUKI, NAKAJIMA TASUKU, KUROKAWA TAKAYUKI, TAKAGI YASUAKI, GONG JIAN PING
    高分子学会予稿集(CD-ROM)  2015/05
  • 銀コーティングを用いた伸縮可能導電性ハイドロゲルの創製  [Not invited]
    TAKAHASHI RIKU, NAKAJIMA TASUKU, NONOYAMA TAKAYUKI, KUROKAWA TAKAYUKI, GONG JIAN PING
    高分子学会予稿集(CD-ROM)  2015/05
  • セルロースを犠牲結合とする高靱性・自己修復性エラストマーの創製  [Not invited]
    MURAI JOJI, NAKAJIMA TASUKU, NONOYAMA TAKAYUKI, KUROKAWA TAKAYUKI, GONG JIAN PING
    高分子学会予稿集(CD-ROM)  2015/05
  • 骨組織との接着を目指したDNゲル表面のHApパターニング  [Not invited]
    KIYAMA RYUJI, NONOYAMA TAKAYUKI, KUROKAWA TAKAYUKI, NAKAJIMA TASUKU, GONG JIAN PING
    高分子学会予稿集(CD-ROM)  2015/05
  • Tough and Self-healing Polyampholyte Hydrogels-Similarity with Glassy Polymers  [Not invited]
    IHSAN ABU BIN, SUN TAO LIN, NONOYAMA TAKAYUKI, NAKAJIMA TASUKU, KUROKAWA TAKAYUKI, GONG JIAN PING
    高分子学会予稿集(CD-ROM)  2015/05
  • Abnormal elastic behaviour of poly(2-ureidoethyl methacrylate) physical hydrogels  [Not invited]
    SUN TAOLIN, NONOYAMA TAKAYUKI, SARUWATARI YOSHIYUKI, LUO FENG, KUROKAWA TAKAYUKI, NAKAJIMA TASUKU, IHSAN ABU BIN, GONG JIAN PING
    高分子学会予稿集(CD-ROM)  2015/05
  • Tough hydrogels with H-bonds as reversible sacrificial bonds  [Not invited]
    SUN TAOLIN, NONOYAMA TAKAYUKI, SARUWATARI YOSHIYUKI, LUO FENG, KUROKAWA TAKAYUKI, NAKAJIMA TASUKU, IHSAN ABU BIN, GONG JIAN PING
    高分子学会予稿集(CD-ROM)  2015/05
  • ダブルネットワークゲルの降伏メカニズムの解明  [Not invited]
    MATSUDA TAKAHIRO, NAKAJIMA TASUKU, KUROKAWA TAKAYUKI, NONOYAMA TAKAYUKI, SAKAI TAKAMASA, CHUNG UNG-IL, GONG JIAN PING
    高分子学会予稿集(CD-ROM)  2015/05
  • Bioadhesion Using Polyampholyte Hydrogel  [Not invited]
    ROY CHANCHAL KUMAR, IHSAN ABU BIN, SUN TAO LIN, NONOYAMA TAKAYUKI, NAKAJIMA TASUKU, KUROKAWA TAKAYUKI, GONG JIAN PING
    高分子学会予稿集(CD-ROM)  2015/05
  • 軟骨再生DNハイドロゲルの骨組織への接着を目指した表面選択的HApパターニング  [Not invited]
    KIYAMA RYUJI, NONOYAMA TAKAYUKI, KUROKAWA TAKAYUKI, NAKAJIMA TASUKU, GONG JIAN PING
    日本セラミックス協会年会講演予稿集(CD-ROM)  2015/03
  • DNハイドロゲルの大変形下におけるHApのミネラリゼーション  [Not invited]
    FUKAO KAZUKI, NONOYAMA TAKAYUKI, KUROKAWA TAKAYUKI, NAKAJIMA TASUKU, GONG JIAN PING
    日本セラミックス協会年会講演予稿集(CD-ROM)  2015/03
  • ハイドロゲルの摩擦と潤滑に及ぼす表面溝形状の効果  [Not invited]
    KOIKE SATOSHI, OZONO TAKUYA, NONOYAMA TAKAYUKI, NAKAJIMA TASUKU, KUROKAWA TAKAYUKI, GONG JIAN PING
    高分子ゲル研究討論会講演要旨集  2015/01
  • 軟骨再生ハイドロゲルと骨組織の接着を目指した高靱性ハイドロゲル表面におけるHApのバイオミネラリゼーション  [Not invited]
    KIYAMA RYUJI, NONOYAMA TAKAYUKI, KUROKAWA TAKAYUKI, NAKAJIMA TASUKU, GONG JIAN PING
    高分子ゲル研究討論会講演要旨集  2015/01
  • マルチシリンダー構造をもつ二分子膜ゲルの機能発現  [Not invited]
    MITO KEI, KUROKAWA TAKAYUKI, NAKAJIMA TASUKU, NONOYAMA TAKAYUKI, GONG JIAN PING
    高分子ゲル研究討論会講演要旨集  2015/01
  • セルロースを犠牲結合とする高靱性・自己回復性ソフトマテリアルの創製  [Not invited]
    MURAI JOJI, NAKAJIMA TASUKU, NONOYAMA TAKAYUKI, KUROKAWA TAKAYUKI, KYO KENHEI
    高分子学会北海道支部研究発表会講演要旨集  2015
  • 力学的刺激が誘起するDNゲル内部の溶液化学反応  [Not invited]
    MATSUDA KODAI, NAKAJIMA TASUKU, KUROKAWA TAKAYUKI, NONOYAMA TAKAYUKI, KYO KENHEI
    高分子学会北海道支部研究発表会講演要旨集  2015
  • Solvent induced photonic on/off swithing in lamellar bilayer hydrogel  [Not invited]
    ILYAS MUHAMMAD, KUROKAWA TAKAYUKI, NAKAJIMA TASUKU, NONOYAMA TAKAYUKI, GONG JIANPING
    高分子学会北海道支部研究発表会講演要旨集  2015
  • 海水を給水源としたゲル上の植物成長システムの開発  [Not invited]
    OTAKE SHUNSUKE, KUROKAWA TAKAYUKI, NAKAJIMA TASUKU, NONOYAMA TAKAYUKI, MIWA KYOKO, KYO KENHEI
    高分子学会北海道支部研究発表会講演要旨集  2015
  • 両性電解質高分子を用いた繊維状高靱性ゲルの創製  [Not invited]
    HOSHINO KEN'ICHI, OKADA MASANORI, SON TORIN, NONOYAMA TAKAYUKI, NAKAJIMA TASUKU, KUROKAWA TAKAYUKI, KYO KENHEI
    高分子学会北海道支部研究発表会講演要旨集  2015
  • 抗菌性ゲルのスクリーニング  [Not invited]
    SHIBATA YUKI, KUROKAWA TAKAYUKI, NONOYAMA TAKAYUKI, NAKAJIMA TASUKU, AIZAWA TOMOYASU, KYO KENHEI
    高分子学会北海道支部研究発表会講演要旨集  2015
  • Two-step polymerization: a novel method for preparing polymer-supported lipid bilayer hydrogel  [Not invited]
    LI XU FENG, NAKAJIMA TASUKU, NONOYAMA TAKAYUKI, KUROKAWA TAKAYUKI, GONG JIAN PING
    高分子学会予稿集(CD-ROM)  2014/09
  • ダブルネットワークゲルの高分子鎖内部破断の化学的証明  [Not invited]
    MATSUDA TAKAHIRO, NAKAJIMA TASUKU, KUROKAWA TAKAYUKI, NONOYAMA TAKAYUKI, GONG JIAN PING
    高分子学会予稿集(CD-ROM)  2014/09
  • Tough and Self-healing Hydrogels from Polyampholytes Based on Reversible Sacrificial Bonds  [Not invited]
    IHSAN ABU BIN, SUN TAO LIN, NONOYAMA TAKAYUKI, NAKAJIMA TASUKU, KUROKAWA TAKAYUKI, GONG JIAN PING
    高分子学会予稿集(CD-ROM)  2014/09
  • 結合性骨形成を目指したHApコート高強度DNハイドロゲル最表面の構造評価  [Not invited]
    NONOYAMA TAKAYUKI, KIYAMA RYUJI, NAKAJIMA TASUKU, KUROKAWA TAKAYUKI, GONG JIAN PING
    高分子学会予稿集(CD-ROM)  2014/09
  • Tough and Self-healing Hydrogels from Polyampholytes: Play with Reversible Sacrificial Bonds  [Not invited]
    IHSAN ABU BIN, SUN TAO LIN, NONOYAMA TAKAYUKI, NAKAJIMA TASUKU, KUROKAWA TAKAYUKI, GONG JIAN PING
    高分子学会予稿集(CD-ROM)  2014/05
  • DNゲルの強靱性に対する数理的考察  [Not invited]
    IKURA YUMIHIKO, NAKAJIMA TASUKU, NONOYAMA TAKAYUKI, KUROKAWA TAKAYUKI, GONG JIAN PING, NAGAYAMA MASAHARU
    高分子学会予稿集(CD-ROM)  2014/05
  • Robust Adhesion of Tough DN Hydrogels on Rough Solid Substrates by 'Graft Gelation'  [Not invited]
    OKAZAKI HARUKA, NAKAJIMA TASUKU, NONOYAMA TAKAYUKI, KUROKAWA TAKAYUKI, GONG JIAN PING
    高分子学会予稿集(CD-ROM)  2014/05
  • 高強度ハイドロゲルとバイオセラミックスの融合:ソフトセラミックスの創製  [Not invited]
    NONOYAMA TAKAYUKI, KIYAMA RYUJI, KUROKAWA TAKAYUKI, NAKAJIMA TASUKU, GONG JIAN PING
    日本セラミックス協会年会講演予稿集(CD-ROM)  2014/03
  • 軟骨再生ハイドロゲルと骨組織の接着を目指した高靱性DNゲル表面におけるHApのバイオミネラリゼーション  [Not invited]
    KIYAMA RYUJI, NONOYAMA TAKAYUKI, KUROKAWA TAKAYUKI, NAKAJIMA TASUKU, GONG JIAN PING
    日本セラミックス協会年会講演予稿集(CD-ROM)  2014/03
  • ゲルの異方的膨潤が誘起する液晶性高分子の超構造形成  [Not invited]
    TAKAHASHI RIKU, NAKAJIMA TASUKU, KUROKAWA TAKAYUKI, NONOYAMA TAKAYUKI, GUN CHEMPIN
    化学系学協会北海道支部冬季研究発表会講演要旨集(CD-ROM)  2014/01
  • A novel anisotropic and tough hydrogel from swim bladder collagen  [Not invited]
    MREDHA MD. TARIFUL ISLAM, ZHANG XI, NONOYAMA TAKAYUKI, NAKAJIMA TASUKU, KUROKAWA TAKAYUKI, HAQUE MD. ANAMUL, TAKAGI YASUAKI, GONG JIAN PING
    高分子ゲル研究討論会講演要旨集  2014/01
  • Reversible and Strong Adhesion of Polyampholyte Hydrogel  [Not invited]
    ROY CHANCHAL KUMAR, ABU BIN IHSAN, SUN TAO LIN, NONOYAMA TAKAYUKI, NAKAJIMA TASUKU, KUROKAWA TAKAYUKI, GONG JIAN PING
    高分子ゲル研究討論会講演要旨集  2014/01
  • Tetra‐PEGゲルを第一網目構造に持つDNゲルの物性評価  [Not invited]
    MATSUDA TAKAHIRO, NAKAJIMA TASUKU, KUROKAWA TAKAYUKI, NONOYAMA TAKAYUKI, SAKAI TAKAMASA, CHUNG UNG-IL, GONG JIAN PING
    高分子ゲル研究討論会講演要旨集  2014/01
  • 繊維状高靱性ゲルの創製  [Not invited]
    HOSHINO KEN'ICHI, SUN TAO LIN, NONOYAMA TAKAYUKI, NAKAJIMA TASUKU, KUROKAWA TAKAYUKI, GONG JIAN PING
    繊維学会予稿集  2014
  • Self-healing behavior of tough hydrogel created by dynamic and reversible sacrificial bonds  [Not invited]
    IHSAN ABU BIN, SUN TAO LIN, NONOYAMA TAKAYUKI, NAKAJIMA TASUKU, KUROKAWA TAKAYUKI, GONG JIAN PING
    高分子学会北海道支部研究発表会講演要旨集  2014
  • Shear Adhesion of Novel Polyampholyte Hydrogel  [Not invited]
    ROY CHANCHAL KUMAR, OKAZAKI HARUKA, IHSAN ABU BIN, SUN TAO LIN, NONOYAMA TAKAYUKI, NAKAJIMA TASUKU, KUROKAWA TAKAYUKI, GONG JIAN PING
    高分子学会北海道支部研究発表会講演要旨集  2014
  • 均一な第一網目構造を持つ超高強度DNゲルの一軸伸長変形挙動解析  [Not invited]
    MATSUDA TAKAHIRO, NAKAJIMA TASUKU, KUROKAWA TAKAYUKI, NONOYAMA TAKAYUKI, SAKAI TAKAMASA, CHUNG UNG-IL, GONG JIAN PING
    エラストマー討論会講演要旨集  2013/12
  • 生体硬組織にならう高靱性DNゲル中でのミネラリゼーション  [Not invited]
    NONOYAMA TAKAYUKI, KIYAMA RYUJI, NAKAJIMA TASUKU, KUROKAWA TAKAYUKI, GONG JIAN PING
    高分子学会予稿集(CD-ROM)  2013/08
  • ペプチドを用いたバイオミネラリゼーションによる無機結晶の成長制御  [Not invited]
    ANDO MASAYUKI, NONOYAMA TAKAYUKI, KINOSHITA TAKATOSHI
    高分子学会予稿集(CD-ROM)  2013/05
  • pHマルチレスポンス型ハイドロゲルの創成とDDSへの応用  [Not invited]
    ICHII SHO, NONOYAMA TAKAYUKI, KINOSHITA TAKATOSHI
    高分子学会予稿集(CD-ROM)  2013/05
  • バイオミネラリゼーションにならう有機・無機界面におけるエピタキシャル性  [Not invited]
    NONOYAMA TAKAYUKI, KINOSHITA TAKATOSHI, HIGUCHI MASAHIRO, SATO KIMIYASU, KATO KATSUYA
    高分子学会予稿集(CD-ROM)  2012/09
  • 骨充填剤に応用可能なリン酸カルシウム含有ペプチドゲルの創成  [Not invited]
    OGASAWARA HOKUTO, NONOYAMA TAKAYUKI, KINOSHITA TAKATOSHI
    高分子学会予稿集(CD-ROM)  2012/09
  • ペプチドの自己組織化を利用した薬物徐放制御システムの開発  [Not invited]
    MURAI KAZUKI, NONOYAMA TAKAYUKI, HIGUCHI MASAHIRO, KATO KATSUYA
    高分子学会予稿集(CD-ROM)  2012/05
  • バイオミネラリゼーションによるペプチド単分子膜上でのリン酸カルシウムの結晶成長  [Not invited]
    NONOYAMA TAKAYUKI, KINOSHITA TAKATOSHI, HIGUCHI MASAHIRO, NAGATA KENJI, SATO KIMIYASU, KATO KATSUYA
    高分子学会予稿集(CD-ROM)  2012/05
  • NONOYAMA TAKAYUKI, KINOSHITA TAKATOSHI, HIGUCHI MASAHIRO, NAGATA KENJI, SATO KIMIYASU, KATO KATSUYA
    日本セラミックス協会年会講演予稿集  2012/03 
    バイオミネラリゼーションにおいて、どの段階で何が無機物の結晶相やモルフォロジーを決定しているかは、結晶学的にも非常に興味深い。事実、骨形成においてハイドロキシアパタイト(HAp) がコラーゲンファイバーに沿って形成されるように、バイオミネラリゼーションプロセスは無機構造を自在に制御する可能性を秘めている。我々はこれまでに、β-シートペプチド単分子膜上でのリン酸カルシウムのミネラリゼーションを通して有機・無機界面におけるエピタキシャルな関係性を調査してきた。β-シートペプチドはアミノ酸側鎖の官能基が 2 次元平面で規則正しく配列している。 今回はHAp の a 面及び c 面のカルシウム原子の位置に対応するように、カルボキシル基を配置した二種類のペプチドを新規設計し、 リン酸カルシウムのミネラリゼーションにおいて、形成した結晶相や結晶方位と対応するかを検証した。
  • pH応答ペプチドを利用した薬物除放制御システムの開発  [Not invited]
    MURAI KAZUYOSHI, NONOYAMA TAKAYUKI, ANDO FUMIO, KATO KATSUYA
    日本セラミックス協会東海支部学術研究発表会講演要旨集  2011/12
  • バイオミネラリゼーションにならうペプチド単分子膜上でのリン酸カルシウムの結晶成長  [Not invited]
    NONOYAMA TAKAYUKI, KINOSHITA TAKATOSHI, HIGUCHI MASAHIRO, NAGATA KENJI, SATO KIMIYASU, KATO KATSUYA
    日本セラミックス協会東海支部学術研究発表会講演要旨集  2011/12
  • 単一シーケンスペプチドを用いたバイオミネラリゼーション挙動の解析  [Not invited]
    KUNO TATSUYA, NONOYAMA TAKAYUKI, HIRAO KIYOSHI, KATO KATSUYA
    日本セラミックス協会東海支部学術研究発表会講演要旨集  2011/12
  • バイオミネラリゼーションにおけるチャージリレー効果  [Not invited]
    KUNO TATSUYA, NONOYAMA TAKAYUKI, HIRAO KIYOSHI, KATO KATSUYA
    中部化学関係学協会支部連合秋季大会講演予稿集  2011/11
  • ペプチドテンプレートによる無機物の結晶相及びモルフォロジー制御  [Not invited]
    NONOYAMA TAKAYUKI, KINOSHITA TAKATOSHI, HIGUCHI MASAHIRO, NAGATA KENJI, SATO KIMIYASU, KATO KATSUYA
    中部化学関係学協会支部連合秋季大会講演予稿集  2011/11
  • 表面機能化メソポーラスシリカ上へのスブチリシンの固定化と表面官能基が酵素触媒特性に与える影響  [Not invited]
    MURAI KAZUKI, NONOYAMA TAKAYUKI, ANDO FUMIO, KATO KATSUYA
    高分子学会予稿集(CD-ROM)  2011/09
  • ペプチドゲル中でのミネラリゼーションにおけるリン酸カルシウムの合成  [Not invited]
    OGASAWARA HOKUTO, NONOYAMA TAKAYUKI, KINOSHITA TAKATOSHI
    高分子学会予稿集(CD-ROM)  2011/09
  • Titanium Dioxide Biomineralization with Peptide Nanofiber  [Not invited]
    NONOYAMA TAKAYUKI, KINOSHITA TAKATOSHI, HIGUCHI MASAHIRO, NAGATA KENJI, SATO KIMIYASU, KATO KATSUYA
    高分子学会予稿集(CD-ROM)  2011/09
  • KUNO TATSUYA, NONOYAMA TAKAYUKI, HIRAO KIYOSHI, KATO KATSUYA
    日本セラミックス協会秋季シンポジウム講演予稿集  2011/09 
    生物が合成し利用するバイオミネラルは、常温常圧の低環境負荷条件で合成され、かつ有機物と複合化することによりナノスケールで制御されている。そのため、このバイオミネラル形成(バイオミネラリゼーション)は近年、省エネと小型化の双方の観点から注目を集めている。このバイオミネラリゼーションの挙動をより深く理解するために、本研究では、二次構造を制御した自己組織化ペプチドを固相合成し、そのペプチドをバイオミネラリゼーションの触媒として利用し、その触媒活性と合成される無機材料の評価を行った。
  • NONOYAMA TAKAYUKI, KINOSHITA TAKATOSHI, HIGUCHI MAYUMI, NAGATA KENJI, SATO KIMIYASU, KATO KATSUYA
    日本セラミックス協会秋季シンポジウム講演予稿集  2011/09 
    有機無機界面において、一方の表面の化学的性質や形状は、他方のそれに大きく影響を与える。つまり表面を高度に設計することで他方の物質を制御できる。今回は、高度に配向秩序化された有機物表面が無機物の結晶相とモルフォロジーに与える影響を調査した。実際にはリン酸カルシウムのミネラリゼーションをシーケンシャルペプチド自己組織化単分子膜上で行いその析出物を透過電子顕微鏡や三次元断層影像法を用いて解析した。今回の基礎的知見は有機無機ハイブリッド材料創成における一つの指針となるかもしれない。
  • KUNO TATSUYA, NONOYAMA TAKAYUKI, HIRAO KIYOSHI, KATO KATSUYA
    日本セラミックス協会年会講演予稿集  2011/03 
    Biominerals such as bone, tooth and shell, prepared under mild conditions, have high mechanical properties. Organic functional groups on the surface of organic matrices like protein, lipid and polysaccharide have an important role for the mineral formation in living body. In order to evaluate the organic functional groups for biomineralization, peptides with single sequence were prepared and their catalytic effects were investigated. In addition, structural properties of silica minerals synthesized with peptide were also evaluated.
  • 固相合成人工ペプチドをテンプレートとするバイオミネラリゼーション挙動の解析  [Not invited]
    KUNO TATSUYA, NONOYAMA TAKAYUKI, HIRAO KIYOSHI, KATO KATSUYA
    日本セラミックス協会東海支部学術研究発表会講演要旨集  2010/12
  • ペプチドスキャフォールドを用いた官能基秩序界面上でのバイオミネラリゼーションによるリン酸カルシウムの結晶形態制御  [Not invited]
    NONOYAMA TAKAYUKI, KINOSHITA TAKATOSHI, HIGUCHI MASAHIRO, SATO KIMIYASU, KATO KATSUYA
    日本セラミックス協会東海支部学術研究発表会講演要旨集  2010/12
  • Peptide-assisted Preparation of Silica Nano Particles and Their Application for Biomolecule Encapsulation  [Not invited]
    KATO KATSUYA, NISHIDA MASAKAZU, NONOYAMA TAKAYUKI, KINOSHITA TAKATOSHI
    日本セラミックス協会秋季シンポジウム講演予稿集  2010/11
  • β‐シートペプチドから成る官能基二次元配向膜上でのミネラリゼーションによるリン酸カルシウムの合成  [Not invited]
    NONOYAMA TAKAYUKI, TANAKA MASAYOSHI, KINOSHITA TAKATOSHI, HIGUCHI MASAHIRO, NAGATA FUKUE, SATO KIMIYASU, KATO KATSUYA
    中部化学関係学協会支部連合秋季大会講演予稿集  2010/11
  • 官能基秩序配列を有したペプチドスキャフォールド上でのミネラリゼーション制御  [Not invited]
    NONOYAMA TAKAYUKI, TANAKA MASAYOSHI, KINOSHITA TAKATOSHI, HIGUCHI MASAHIRO, NAGATA FUKUE, SATO KIMIYASU, KATO KATSUYA
    日本化学会バイオテクノロジー部会シンポジウム講演要旨集  2010/09
  • 官能基秩序配列を有したペプチドスキャフォールド上でのミネラリゼーションによるリン酸カルシウムの合成  [Not invited]
    NONOYAMA TAKAYUKI, TANAKA MASAYOSHI, KINOSHITA TAKATOSHI, HIGUCHI MASAHIRO, NAGATA FUKUE, SATO KIMIYASU, KATO KATSUYA
    高分子学会予稿集(CD-ROM)  2010/09
  • ペプチドテンプレート上でのミネラリゼーションによるリン酸カルシウム合成  [Not invited]
    NONOYAMA TAKAYUKI, KINOSHITA TAKATOSHI, NAGATA FUKUE, SATO KIMIYASU, KATO KATSUYA
    高分子学会予稿集(CD-ROM)  2010/05
  • ペプチドテンプレート上でのミネラリゼーションによるリン酸カルシウム合成  [Not invited]
    NONOYAMA TAKAYUKI, KINOSHITA TAKATOSHI, NAGATA FUKUE, SATO KIMIYASU, KATO KATSUYA
    日本セラミックス協会年会講演予稿集  2010/03
  • Nonoyama Takayuki, Nagata Fukue, Sato Kimiyasu, Kato Katsuya, Kinoshita Takatoshi
    Preprints of Annual Meeting of The Ceramic Society of Japan
    Preprints of Fall Meeting of The Ceramic Society of Japan  2010 
    有機鎖官能基が空間的に厳密に配置されたペプチドテンプレートを用いて、リン酸カルシウムのミネラリゼーションを行った。β-シート型ペプチド(LE)8-PEG70はグルタミン酸(E)とロイシン(L)の交互シークエンスにより設計し浸漬法により単分子膜を調製した。この基板上に酢酸カルシウム水溶液とリン酸水素二アンモニウム水溶液を交互に滴下しリン酸カルシウムを析出させた。AFM測定により、ペプチドによる等間隔のファイバー構造が観察された。溶液濃度Ca 50 mM, P 30 mMのとき、高配向のナノレーン状析出物がSEM測定より確認された。XPS、TEMおよびED測定からリン酸カルシウムの析出物はアモルファスであることが明らかになった。さらに析出の初期段階において析出形態の違いが確認された。
  • 核酸塩基対を利用したβ‐シートペプチド自己組織化膜上への金ナノ粒子の固定化と配列制御  [Not invited]
    NONOYAMA TAKAYUKI, HIGUCHI MASAHIRO, TANAKA MASAYOSHI, KINOSHITA TAKATOSHI
    高分子学会予稿集(CD-ROM)  2009/09
  • ペプチドファイバーゲルによるアルブミンの認識  [Not invited]
    NONOYAMA TAKAYUKI, SAITO AI, TANAKA MASAYOSHI, KINOSHITA TAKATOSHI
    繊維学会夏季セミナー講演要旨集  2009/08
  • ペプチド自己組織化ナノファイバー上への金ナノ粒子の選択的固定化  [Not invited]
    NONOYAMA TAKAYUKI, HIGUCHI MASAHIRO, TANAKA MASAYOSHI, KINOSHITA TAKATOSHI
    繊維学会夏季セミナー講演要旨集  2009/08
  • 相補的水素結合を利用したβ‐シートペプチド自己組織化膜上への金ナノ粒子の固定化  [Not invited]
    NONOYAMA TAKAYUKI, TANAKA MASAYOSHI, KINOSHITA TAKATOSHI
    高分子学会予稿集(CD-ROM)  2009/05
  • 相補的水素結合を利用したβ‐シートペプチド自己組織化膜上への金ナノ粒子の固定化  [Not invited]
    NONOYAMA TAKAYUKI, TANAKA MASAYOSHI, KINOSHITA TAKATOSHI
    高分子学会予稿集(CD-ROM)  2008/09

MISC

Awards & Honors

  • 2022/06 Ceramics Society of Japan The Ceramics Society of Japan (CerSJ) Awards for advancements in ceramic science and technology
     生体無機-高分子ゲル融合体による骨形成機序と骨再生誘導の研究
  • 2020/09 Ceramics Society of Japan Presentation Award for Young Researcher in CSJ Fall Meeting
     バイオミネラルをエネルギー散逸項とするハイドロゲルの強靭化 
    受賞者: Takayuki Nonoyama
  • 2019/05 Society of Polymer Science, Japan Award for Encouragement of Research in Polymer Science
     高靱性ゲル・バイオセラミックスの複合と骨形成誘導に関する研究 
    受賞者: nonoyamatakayuki
  • 2018/09 Society of Polymer Science, Japan Publicity Award
     高温で瞬時に1000倍以上硬くなる温度応答性アクティブソフトマテリアル 
    受賞者: nonoyamatakayuki
  • 2017/09 Ceramics Society of Japan Presentation Award for Young Researchers
     Interpenetrating Structure of Natural Bone Tissue & Synthesized Hydrogel 
    受賞者: nonoyamatakayuki
  • 2014/10 International Union of Materials Research Societies International Union of Materials Research Societies- International Conference in Asia, The Award for Encouragement of Research in IUMRS-ICA2014
     
    受賞者: nonoyamatakayuki
  • 2013/03 Nagoya Institute of Technology President award in Nagoya Institute of Technology
     
    受賞者: nonoyamatakayuki
  • 2012/05 Ceramics Society of Japan The best presentation award
     
    受賞者: nonoyamatakayuki
  • 2012/03 Nagoya Institute of Technology President award in Nagoya Institute of Technology
     
    受賞者: nonoyamatakayuki
  • 2011/12 Tokai BO, Ceramics Society of Japan The best presentation award
     
    受賞者: nonoyamatakayuki
  • 2011/11 Union of Chemistry-Related Societies in Chubu Area Presentation award in Tokai BO of SPSJ
     
    受賞者: nonoyamatakayuki
  • 2011/09 Tokai BO, Society of Polymer Science, Japan Presentation award
     
    受賞者: nonoyamatakayuki
  • 2011/07 Tokai BO, Ceramics Society of Japan The best discussion award
     
    受賞者: nonoyamatakayuki
  • 2011/07 Tokai BO, Ceramics Society of Japan Presentation award
     
    受賞者: nonoyamatakayuki
  • 2011/03 Nagoya Institute of Technology Vice President award in Nagoya Institute of Technology
     
    受賞者: nonoyamatakayuki
  • 2011/01 Ceramics Society of Japan World young fellow meeting 2011 Presentation award
     
    受賞者: nonoyamatakayuki
  • 2010/07 Tokai BO, Ceramics Society of Japan The best presentation award
     
    受賞者: nonoyamatakayuki

Research Grants & Projects

  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Fund for the Promotion of Joint International Research (International Leading Research )
    Date (from‐to) : 2022/12 -2029/03 
    Author : グン 剣萍, Li Xiang, 野々山 貴行, 中島 祐
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (S)
    Date (from‐to) : 2022/04 -2027/03 
    Author : グン 剣萍, 中島 祐, 印出井 努, 野々山 貴行
  • 工業リグニンの構造-物性相関の解明と高機能材料化技術の創出
    国立研究開発法人 科学技術振興機構:ALCA-Next
    Date (from‐to) : 2023/11 -2027/03 
    Author : 鈴木 栞, 野々山 貴行, 徳永 有希
  • 生物に習う高温でガラス化する高分子材料の創製とその学理解明
    Japan Science and Technology Agency:Fusion Oriented REsearch for disruptive Science and Technology (FOREST)
    Date (from‐to) : 2021/04 -2027/03
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research
    Date (from‐to) : 2021/04 -2026/03 
    Author : 野々山 貴行
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
    Date (from‐to) : 2022/04 -2025/03 
    Author : グン 剣萍, 印出井 努, 野々山 貴行, キング ダニエル, 中島 祐
  • 日本学術振興会:科学研究費助成事業 基盤研究(B)
    Date (from‐to) : 2021/04 -2024/03 
    Author : 津田 真寿美, 野々山 貴行, 田中 伸哉
     
    がんの再発は、がん治療に耐性を示すがん幹細胞が生き残ることによって起きる。がんの根絶には、がん組織におけるがん幹細胞の誕生・生存機構の解明が必須であるが、がん幹細胞が微量なことに加えて、従来のポリスチレンdish上でのがん細胞単独培養法は生体内のがん組織環境と大きく乖離しており、真の解明に至っていない。研究代表者らは、近年、高強度ダブルネットワークゲル(DNゲル)上にがん細胞を播種すると、24時間以内に迅速にがん幹細胞が誘導されるリプログラミング(初期化)現象を見出した(Nat. Biomed. Eng., 2021)。当該技術を基盤として、本研究ではがん組織におけるがん幹細胞の誕生・生存機序の解明を目指す。 令和3年度は、高頻度に再発を引き起こす肉腫の生体内環境を模倣するために、高強度DNゲルの作製技術と多孔質ゲルを得る凍結重合法を組み合わせて、高強度多孔質(ポーラス)ゲルを作製した。ポーラスゲルは、1st モノマーにアニオン性高分子NaAMPSを用い、2ndモノマーに中性高分子AAmを用いた。筋組織を模倣するため、細胞外基質としてフィブロネクチンを吸着後、GFPラベル筋芽細胞を播種し、細胞の接着や長期生存を検討した。AAmの濃度を変えることでポーラスサイズを調整し、さらに細胞の播種方法を改善することにより、ポーラスゲルの深部まで細胞が進展するよう3次元組織モデルを最適化した。このポーラスゲルをマウスの筋肉内に埋植すると、1週間以内に宿主細胞がゲル内に侵入して組織を復元した。一方、氷の成長方向を制御するフリーズキャスティング法を用いた凍結重合法により、筋組織を模倣した高度な配向構造を有するポーラスゲルの創製に成功した。
  • Japan Society for the Promotion of Science:Grant-in-Aid for Scientific Research (S)
    Date (from‐to) : 2017/05 -2022/03 
    Author : Jian Ping Gong
     
    ハード相を犠牲結合とする複合材料では、プラスチックの三次元格子によるハード相と水中における膨潤能を有するハイドロゲルによるソフト相を用い、ソフト相とハード相のポアソン比ミスマッチが複合材料の膨潤・力学特性に与える影響を解析した。ハイドロゲルは、溶媒に浸漬させると溶媒を取り込んで膨潤(体積変化)する性質を持つ。ハード相にジャングルジム型構造を採用した複合材料を溶媒に浸漬させた場合、そのジャングルジム型構造がソフト相の膨潤に全く追随出来ないため、ソフト相の膨潤に伴ってハード相の構造が崩壊し、弾性率・強度が大きく損なわれる。一方、ハード相に負のポアソン比を持つオーセチック構造を採用した場合、ソフト相の膨潤収縮にハード相が追随可能であるため、複合材料が膨潤または収縮しても構造崩壊が起こらず、優れた力学特性が保たれることが見いだされた。 続いてソフト相を犠牲結合とする複合材料では、ソフト相の局所的大変形による粘弾性効果が、ソフト複合材料を大きく強靭化していることを見出した。複合材料の幅が狭い場合、その亀裂進行は、ソフト相からハード相(繊維)が引き抜かれることに起因するソフト相の破断により生じることが見いだされた。ここで、繊維引き抜きが起こる部位ではソフト相が局所的に高速で大変形し、粘性的なエネルギー散逸が生じることで、材料の引裂エネルギーが極めて高くなると予想された。我々は、この局所的な粘性散逸の効果を表す半経験的な式を導いた。本式に従い、ソフト相単独の機械的特性とハード相の構造因子を最適化することで、粘性散逸の効果を増大させ、本タイプのソフト複合材料の靭性をさらに高めることに成功した。
  • Fabrication of Soft Photonic Crystals for Novel Functions
    Japan Society for the Promotion of Science:Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
    Date (from‐to) : 2017/06 -2022/02 
    Author : Jian Ping Gong
  • Isochoric Hydrogel Possessing Thermal Toughening
    Japan Society for the Promotion of Science:Grant-in-Aid for Challenging Research (Exploratory)
    Date (from‐to) : 2017/06 -2020/03 
    Author : nonoyamatakayuki
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research
    Date (from‐to) : 2017/04 -2018/03 
    Author : グン 剣萍, 黒川 孝幸, 中島 祐, 野々山 貴行, キング ダニエル
     
    本研究では、高靭性ゲルの力学挙動(引張試験で見られる降伏現象、弾性率の低下を伴うヒステリシス現象、および引裂試験で見られる亀裂周辺の降伏領域(内部破壊領域)の形成)の三つの特徴を評価することによって、ゲルの靭性及びその高靭性化機構を解明することを目的とした。研究機関内には、ポリアンフォライトゲル/グラスファイバー織物の複合体について、様々な幅のサンプルを作製して引裂試験を行い、破壊エネルギーと降伏領域の関係を見積もった。サンプルの幅が降伏領域のサイズ(~cm)より小さい場合、複合体の破壊エネルギーはサンプルの幅と正の相関があった。一方、サンプルの幅が降伏領域より大きい場合、複合体の破壊エネルギーはサンプルの幅に依存しなかった。これは、本複合体の異常に高い破壊エネルギーが、亀裂近傍の降伏領域形成によるエネルギー散逸によることを強く示唆する結果である。また、破壊されたサンプルを走査型電子顕微鏡で観察した結果、繊維近傍におけるゲル層の破壊が確認された。ここから、本複合体の変形時には、ゲル-繊維間の応力伝達により、ゲル層の変形と破壊によるエネルギー散逸が高効率で発生し、それが本複合体を高効率にタフ化していることが示唆された。
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research
    Date (from‐to) : 2012/05 -2017/03 
    Author : Gong Jian Ping, NONOYAMA Takayuki, SUN Taolin
     
    Gels have been anticipated as tissue-like functional materials, but generally they are mechanically too weak to be applied widely. On the other hand, recently our group has proposed "sacrificial bond principle", where toughness of gels can be effectively improved by introducing weak and brittle bonds into soft and stretchable networks. In this project, we have created a series of extremely tough gels using this principle, e.g., variants of double network gels featuring covalent sacrificial bonds, polyampholyte gels containing ionic sacrificial bonds, and phase-separated polyacrylamide gels exhibiting super toughness based on solvophobic sacrificial bonds. We have also succeeded in adding functions corresponding to chemical species of sacrificial bonds to the tough gels, e.g., self-healing properties to polyampholyte gels and bioactivity to double network gels containing biopolymers. Through these studies, we have confirmed generality and diversity of sacrificial bond principle.
  • 高強度ハイドロゲル中でのリン酸カルシウムのバイオミネラリゼーション
    Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research
    Date (from‐to) : 2014/04 -2017/03 
    Author : Takayuki Nonoyama

Educational Activities

Teaching Experience

  • PhysicsPhysics Hokkaido university
  • Physics I
    開講年度 : 2021
    課程区分 : 学士課程
    開講学部 : 全学教育
    キーワード : 運動、力、運動の法則、仕事、エネルギー、運動量、保存則、剛体、流体、単振動


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