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Development of tendon/ligament repair modulater using a chemically modified Tetra-PEG gel with signal transduction capability

Research Project

Project/Area Number 23K18325
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
Research InstitutionThe University of Tokyo

Principal Investigator

Saito Taku  東京大学, 医学部附属病院, 准教授 (30456107)

Co-Investigator(Kenkyū-buntansha) 酒井 崇匡  東京大学, 大学院工学系研究科(工学部), 教授 (70456151)
岩永 康秀  東京大学, 大学院工学系研究科(工学部), 特任助教 (80906610)
Project Period (FY) 2023-06-30 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2024: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2023: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords整形外科学 / 変形性関節症 / 腱 / 靭帯 / 腱靭帯修復
Outline of Research at the Start

申請者らはシングルセル技術を駆使した解析によって、腱靭帯の修復過程を指揮する新規Progenitorを同定し、腱靭帯の恒常性維持や修復の制御機構を理解するに至った。並行して申請者らは、二種類のPEGを混合して均一な網目構造を有するゲルを術野で瞬時に形成する技術、Tetra-PEGゲルを応用し、腱癒着防止技術の開発を進めている。このゲルに化学修飾を施す技術が確立したことから、本研究では、Tetra-PEGゲルに化学修飾を施し、腱靭帯の制御シグナルを適切に操作することによって、腱靭帯の慢性炎症を抑制し、理想的な修復を誘導するInjectable Gel Systemの開発を目指す。

Outline of Final Research Achievements

Tendons and ligaments are crucial supporting tissues that form joints and support movement, but their degeneration is a fundamental cause of various musculoskeletal degenerative diseases such as osteoarthritis and spondylosis. Degeneration of tendons and ligaments can result from overuse, menopause, and aging. In this study, we successfully identified a factor that induces degeneration and ectopic chondrogenesis during the tendon healing process. Furthermore, we succeeded in using a sustained-release formulation involving a Tetra-PEG gel formed instantly at the surgical site by mixing two types of PEG to create a uniform network structure as a delivery system. Using this hydrogel containing neutralizing antibodies targeting the identified factor, we found that tendon healing in rats was significantly improved.

Academic Significance and Societal Importance of the Research Achievements

オーバーユースや加齢、閉経などで腱・靭帯の恒常性が破綻することは、様々な運動器疾患を引き起こす共通の根源となっている可能性が高いが、腱・靭帯の修復を修飾しうる手段はないため、腱・靭帯障害には有効な治療法はなく、変形性関節症などは予防することもできない。本研究の成果は、腱・靭帯障害のみならず、変形性関節症など運動器変性疾患に広く応用できる可能性がある。

Report

(3 results)
  • 2024 Annual Research Report   Final Research Report ( PDF )
  • 2023 Research-status Report
  • Research Products

    (12 results)

All 2025 2024 2023 Other

All Journal Article (11 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 11 results,  Open Access: 10 results) Remarks (1 results)

  • [Journal Article] CD34hi subset of synovial fibroblasts contributes to fibrotic phenotype of human knee osteoarthritis2025

    • Author(s)
      Miyahara J、Omata Y、Chijimatsu R、Okada H、Ishikura H、Higuchi J、Tachibana N、Nagata K、Tani S、Kono K、Kawaguchi K、Yamagami R、Inui H、Taketomi S、Iwanaga Y、Terashima A、Yano F、Seki M、Suzuki Y、Baron R、Tanaka S、Saito T
    • Journal Title

      JCI Insight

      Volume: 10 Issue: 2

    • DOI

      10.1172/jci.insight.183690

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Acquired Osteomalacia Associated with Autoantibodies against PHEX2025

    • Author(s)
      Hoshino Yoshitomo、Okamoto Kazuo、Ogawa Tomohiro、Kato Hajime、Irie Koki、Watanabe So、Kimura Soichiro、Hidaka Naoko、Kinoshita Yuka、Kobayashi Hiroshi、Hagiwara Daisuke、Kogawa Masakazu、Takayanagi Hiroshi、Tanaka Sakae、Nangaku Masaomi、Makita Noriko、Burbelo Peter D.、Saito Taku、Ito Nobuaki
    • Journal Title

      New England Journal of Medicine

      Volume: 392 Issue: 5 Pages: 513-515

    • DOI

      10.1056/nejmc2405746

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Aging and cell expansion enhance microRNA diversity in small extracellular vesicles produced from human adipose-derived stem cells2024

    • Author(s)
      Tsubaki Toshiya、Chijimatsu Ryota、Takeda Taiga、Abe Maki、Ochiya Takahiro、Tsuji Shinsaku、Inoue Keita、Matsuzaki Tokio、Iwanaga Yasuhide、Omata Yasunori、Tanaka Sakae、Saito Taku
    • Journal Title

      Cytotechnology

      Volume: 77 Issue: 1 Pages: 15-15

    • DOI

      10.1007/s10616-024-00675-6

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Disulfiram ameliorates bone loss in ovariectomized mice by suppressing osteoclastogenesis2024

    • Author(s)
      Fukui Tatsuyuki、Terashima Asuka、Omata Yasunori、Chijimatsu Ryota、Okamoto Kazuo、Tsukasaki Masayuki、Fukuda Yukiko、Hayata Tadayoshi、Saitoh Akiyoshi、Toda Etsuko、Takayanagi Hiroshi、Tanaka Sakae、Terashima Yuya、Saito Taku
    • Journal Title

      Journal of Bone and Mineral Metabolism

      Volume: 43 Issue: 2 Pages: 61-73

    • DOI

      10.1007/s00774-024-01555-x

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Latent metabolic bone disease, skeletal dysplasia and other conditions related to low bone formation among 38 patients with subtrochanteric femoral fractures: a retrospective observational study2024

    • Author(s)
      Kimura Soichiro、Sunouchi Takashi、Watanabe So、Hoshino Yoshitomo、Hidaka Naoko、Kato Hajime、Takeda Shu、Nangaku Masaomi、Makita Noriko、Azuma Kotaro、Kojima Taro、Matsubara Takehiro、Saito Taku、Ito Nobuaki
    • Journal Title

      Osteoporosis International

      Volume: 35 Issue: 9 Pages: 1633-1643

    • DOI

      10.1007/s00198-024-07168-4

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Baricitinib ameliorates inflammatory and neuropathic pain in collagen antibody-induced arthritis mice by modulating the IL-6/JAK/STAT3 pathway and CSF-1 expression in dorsal root ganglion neurons2024

    • Author(s)
      Makabe Kenta、Okada Hiroyuki、Tachibana Naohiro、Ishikura Hisatoshi、Ito Norihito、Tanaka Masaru、Chijimatsu Ryota、Terashima Asuka、Yano Fumiko、Asaka Meiko、Yanagihara Dai、Taketomi Shuji、Matsumoto Takumi、Tanaka Sakae、Omata Yasunori、Saito Taku
    • Journal Title

      Arthritis Research & Therapy

      Volume: 26 Issue: 1 Pages: 121-121

    • DOI

      10.1186/s13075-024-03354-1

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Percolation-induced gel-gel phase separation in a dilute polymer network2023

    • Author(s)
      Ishikawa Shohei、Iwanaga Yasuhide、Uneyama Takashi、Li Xiang、Hojo Hironori、Fujinaga Ikuo、Katashima Takuya、Saito Taku、Okada Yasushi、Chung Ung-il、Sakumichi Naoyuki、Sakai Takamasa
    • Journal Title

      Nature Materials

      Volume: 22 Issue: 12 Pages: 1564-1570

    • DOI

      10.1038/s41563-023-01712-z

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Subcutaneously Transplanted Fresh Cartilage in Allogeneic and Xenogeneic Immunocompetent Mouse2023

    • Author(s)
      Uto Sakura、Hikita Atsuhiko、Mori Daisuke、Sakamoto Tomoaki、Yano Fumiko、Ohba Shinsuke、Saito Taku、Takato Tsuyoshi、Hoshi Kazuto
    • Journal Title

      Tissue Engineering Part A

      Volume: 29 Issue: 19-20 Pages: 541-556

    • DOI

      10.1089/ten.tea.2023.0052

    • Related Report
      2023 Research-status Report
    • Peer Reviewed
  • [Journal Article] Interstitial-fluid shear stresses induced by vertically oscillating head motion lower blood pressure in hypertensive rats and humans2023

    • Author(s)
      Murase Shuhei、Sakitani Naoyoshi、Maekawa Takahiro、Yoshino Daisuke、Takano Kouji、Konno Ayumu、Hirai Hirokazu、Saito Taku、et al
    • Journal Title

      Nature Biomedical Engineering

      Volume: 7 Issue: 11 Pages: 1350-1373

    • DOI

      10.1038/s41551-023-01061-x

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A common variant rs2054564 in ADAMST17 is associated with susceptibility to lumbar spondylosis2023

    • Author(s)
      Taniguchi Yuki、Akune Toru、Nishida Nao、Omori Go、HA Kim、Ueno Kazuko、Saito Taku、Oichi Takeshi、Koike Asako、Mabuchi Akihiko、Oka Hiroyuki、Muraki Shigeyuki、Oshima Yasushi、Kawaguchi Hiroshi、Nakamura Kozo、Tokunaga Katsushi、Tanaka Sakae、Yoshimura Noriko
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 4900-4900

    • DOI

      10.1038/s41598-023-32155-w

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Nutrient-regulated dynamics of chondroprogenitors in the postnatal murine growth plate.2023

    • Author(s)
      Oichi T, Kodama J, Wilson K, Tian H, Imamura Kawasawa Y, Usami Y, Oshima Y, Saito T, Tanaka S, Iwamoto M, Otsuru S, Enomoto-Iwamoto M.
    • Journal Title

      Bone Research

      Volume: 11 Issue: 1 Pages: 20-20

    • DOI

      10.1038/s41413-023-00258-9

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Remarks] 東京大学医学部附属病院 整形外科・脊椎外科

    • URL

      http://www.u-tokyo-ortho.jp/

    • Related Report
      2024 Annual Research Report 2023 Research-status Report

URL: 

Published: 2023-07-04   Modified: 2026-01-16  

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