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Development of in vivo-like 3D vascularized osteochondral tissue

Research Project

Project/Area Number 20K09504
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56020:Orthopedics-related
Research InstitutionOsaka University

Principal Investigator

Shimomura Kazunori  大阪大学, 大学院医学系研究科, 招へい教員 (40755998)

Co-Investigator(Kenkyū-buntansha) 松崎 典弥  大阪大学, 大学院工学研究科, 教授 (00419467)
中村 憲正  大阪大学, 国際医工情報センター, 招へい教授 (50273719)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords骨軟骨再生 / 三次元組織 / 骨軟骨組織 / 血管構造 / 軟骨再生 / 骨再生 / 変形性関節症 / 生体内類似構造 / 生態内類似構造 / 整形外科 / 血管網 / 軟骨 / 骨 / 関節モデル
Outline of Research at the Start

変形性関節症は患者QOLを著しく損なうが、未だに有効な治療法は無いのが現状である。近年、組織工学的手法の進歩により三次元組織・臓器の再生に注目が集まっており、関節症治療への応用が期待されている。我々はこれまでに、細胞外基質の成分であるフィルロネクチンやゼラチンを細胞表面に形成させ、細胞の種類や配置を三次元的に積層させる技術を開発し、様々な三次元組織の作成に成功している。本研究では、これらの技術の応用により、生体に類似した三次元関節モデルを作成し、本三次元モデルを利用した変形性関節症治療法の開発を目指す。

Outline of Final Research Achievements

In this study, we aimed to create a three-dimensional (3D) osteochondral model with the structures and functions, similar to those in vivo. For the cartilage layer, human chondrocytes were seeded in a newly developed photocrosslinkable hydrogel and type 2 collagen, and a hyaline cartilage-like 3D tissue was successfully created. For the bone layer, human mesenchymal stem cells and human umbilical vein endothelial cells were co-cultured in type 1 collagen, and a bone-like tissue with a 3D vascular network was also successfully created. Although there is some rooms for further improvement of the bone layer, the present results have led to the creation of the desired 3D model.

Academic Significance and Societal Importance of the Research Achievements

in vitroで生体に類似した三次元骨軟骨組織を作成することにより、in vivoでの動物実験を減らすことが可能となり、本三次元モデルを用いた変形性関節症の分子メカニズムの解明や新規変形性関節症治療薬の開発のための薬剤スクリーニングの系の確立、さらには本三次元組織を用いた新たな骨軟骨再生治療の開発へ繋がる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (33 results)

All 2023 2022 2021 2020

All Journal Article (12 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 11 results,  Open Access: 3 results) Presentation (10 results) (of which Int'l Joint Research: 1 results,  Invited: 6 results) Book (11 results)

  • [Journal Article] Utilization of Orthobiologic Augmentation for Meniscal Repairs: Current Concepts and Future Perspectives.2023

    • Author(s)
      Shimomura K, Jacob G, Hanai H, Nakamura. N
    • Journal Title

      Journal of Cartilage & Joint Preservation.

      Volume: - Issue: 2 Pages: 100090-100090

    • DOI

      10.1016/j.jcjp.2022.100090

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Freeze Dried Noncoagulating Platelet-Derived Factor Concentrate is a Safe and Effective Treatment for Early Knee Osteoarthritis.2023

    • Author(s)
      Ohtsuru T, Otsuji M, Nakanishi J, Lyman S, Hanai H, Shimomura K, Ando W, Nakamura N.
    • Journal Title

      Knee Surg Sports Traumatol Arthrosc.

      Volume: -

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Five-year outcomes following implantation of a scaffold-free tissue-engineered construct generated from autologous synovial mesenchymal stromal cells for repair of knee chondral lesions.2023

    • Author(s)
      Shimomura K, Ando W, Hart DA, Yonetani Y, Horibe S, Nakamura N.
    • Journal Title

      Orthop J Sports Med.

      Volume: -

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 解剖学的長方形骨孔前十字靱帯再建術における移植腱の違いによる成績比較 -骨付き膝蓋腱vs骨付き大腿四頭筋腱-2023

    • Author(s)
      下村和範 米谷泰一 田中綾香 辻井聡 濱田雅之
    • Journal Title

      JOSKAS

      Volume: -

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Clinical Safety and Effectiveness of Adipose-Derived Stromal Cell vs Stromal Vascular Fraction Injection for Treatment of Knee Osteoarthritis: 2-Year Results of Parallel Single-Arm Trials2022

    • Author(s)
      Yokota Naomasa、Lyman Stephen、Hanai Hiroto、Shimomura Kazunori、Ando Wataru、Nakamura Norimasa
    • Journal Title

      The American Journal of Sports Medicine

      Volume: 50 Issue: 10 Pages: 2659-2668

    • DOI

      10.1177/03635465221107364

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Two uncommon complications related to suture knots after meniscal all-inside suture repair: A case report.2022

    • Author(s)
      Tanaka A, Tsujii A, Shimomura K, Yonetani Y, Hamada M.
    • Journal Title

      JBJS Case Connect.

      Volume: 12 Issue: 3

    • DOI

      10.2106/jbjs.cc.22.00014

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Editorial: Tissue Engineering and Cell Therapy for Cartilage Restoration.2022

    • Author(s)
      Fernandes TL, Bueno DF, Shimomura K, Shao Z, Gomoll AH.
    • Journal Title

      Front Cell Dev Biol.

      Volume: 10 Pages: 947588-947588

    • DOI

      10.3389/fcell.2022.947588

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Posterior Ankle Impingement Caused by Hyaline-like Cartilage Generation in Ballet Dancers -A Report of 2 Cases.2021

    • Author(s)
      Kinugasa K, Shimomura K, Tachibana Y, Hiramatsu K, Horibe S, Shino K, Tanaka Y
    • Journal Title

      J Foot Ankle Surg

      Volume: in press Issue: 4 Pages: e9-e14

    • DOI

      10.1053/j.jfas.2021.10.015

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Tissue Wrapping Augmentation for Anterior Cruciate Ligament Reconstruction: A Review of Clinical Literature.2021

    • Author(s)
      Jacob G, Shimomura K, Yogesh K, Nakamura N
    • Journal Title

      Biologic Orthopedics Journal.

      Volume: in press Issue: SP2 Pages: e1-e6

    • DOI

      10.22374/boj.v3isp2.31

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Histological Analysis of Cartilage Defects Repaired with an Autologous Human Stem-cell Construct 48 Weeks Post-Implantation Reveals Structural Details not Detected by T2 Mapping MRI.2021

    • Author(s)
      Shimomura K, Hamada H, Hart DA, Ando W, Nishii T, Trattnig S, Nehrer S, Nakamura N.
    • Journal Title

      Cartilage

      Volume: in press Issue: 1_suppl Pages: 694S-706S

    • DOI

      10.1177/1947603521989423

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Osteochondral Injury, Management and Tissue Engineering Approaches.2020

    • Author(s)
      Jacob G, Shimomura K, Nakamura N.
    • Journal Title

      Front Cell Dev Biol.

      Volume: 8 Pages: 580868-580868

    • DOI

      10.3389/fcell.2020.580868

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Potential of soluble decellularized extracellular matrix for musculoskeletal tissue engineering - comparison of various mesenchymal tissues -2020

    • Author(s)
      Hanai H, Jacob G, Nakagawa S, Tuan RS, Nakamura N, Shimomura K
    • Journal Title

      Front Cell Dev Biol.

      Volume: 8 Pages: 581972-581972

    • DOI

      10.3389/fcell.2020.581972

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Five-year Outcome of a Scaffold-free Mesenchymal Stem Cell-based Tissue-engineered Construct for Repair of Knee Chondral Lesion.2022

    • Author(s)
      Shimomura K, Ando W, Hart DA, Yonetani Y, Horibe S, Nakamura N.
    • Organizer
      The 16th World Congress of the International Cartilage Repair and Joint Preservation Society
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Comparison of clinical outcomes after anatomic rectangular tunnel anterior cruciate ligament reconstruction with an autograft between bone-patellar tendon-bone and quadriceps tendon.2022

    • Author(s)
      Shimomura K, Yonetani Y, Tanaka A, Tsujii A, Hamada M.
    • Organizer
      JOSKAS-JOSSM 2022
    • Related Report
      2022 Annual Research Report
  • [Presentation] 軟骨再生の現状と将来展望(シンポジウム:新時代の膝温存治療を考える)2022

    • Author(s)
      下村和範、中村憲正
    • Organizer
      第139回 中部日本整形外科災害外科学会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 滑膜間葉系幹細胞を用いた軟骨再生(シンポジウム:半月板・軟骨再生のバイオメカニクス)2022

    • Author(s)
      下村和範、中村憲正
    • Organizer
      第49回 日本臨床バイオメカニクス学会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] スキャフォールドフリー滑膜間葉系幹細胞由来三次元人工組織を用いた軟骨再生(シンポジウム:スポーツ損傷に対するバイオセラピー・再生医療)2022

    • Author(s)
      下村和範、中村憲正
    • Organizer
      第33回 日本臨床スポーツ医学会学術集会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 解剖学的長方形骨孔前十字靱帯再建術における移植腱の違いによる臨床成績の比較 -骨付き大腿四頭筋腱 vs 骨付き膝蓋腱-2022

    • Author(s)
      下村和範、辻井聡、米谷泰一
    • Organizer
      第33回 日本臨床スポーツ医学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] ナノレベル線維構造を有するスキャフォールドを用いた新たな半月板治療法の確立- 変形性関節症の予防を目指して -2022

    • Author(s)
      下村和範
    • Organizer
      第21回日本再生医療学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] Enhanced Repair of Meniscal Hoop Structure Injuries Using An Aligned Electrospun Nanofibrous Scaffold Combined with a Mesenchymal Stem Cell-derived Tissue Engineered Construct2021

    • Author(s)
      Kazunori Shimomura, Benjamin B. Rothrauff, David A. Hart, Shuichi Hamamoto, Masato Kobayashi, Hideki Yoshikawa, Rocky S. Tuan, Norimasa Nakamura
    • Organizer
      第26回日本軟骨代謝学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Cartilage Regeneration by a Scaffold-Free Tissue-Engineered Construct Generated From Autologous Synovial Mesenchymal Stem Cells(シンポジウム)2021

    • Author(s)
      Kazunori Shimomura, Norimasa Nakamura
    • Organizer
      第36回日本整形外科学会基礎学術集会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Cartilage Regeneration by a Scaffold-Free Tissue-Engineered Construct Generated From Autologous Synovial Mesenchymal Stem Cells.2020

    • Author(s)
      Shimomura K, Ando W, Nakamura N.
    • Organizer
      JOSKAS-JOSSM 2020
    • Related Report
      2020 Research-status Report
    • Invited
  • [Book] 膝関節鏡視下手術 (ビジュアル・サージカルテクニック) Chapter 4 診断:正常膝関節の鏡視所見2021

    • Author(s)
      下村和範、中村憲正
    • Total Pages
      5
    • Publisher
      文光堂
    • Related Report
      2021 Research-status Report
  • [Book] ISAKOS/ICRS Book “Cartilage Injury of the Knee” Chapter 20: Role of MSCs in Symptomatic Cartilage Defects2021

    • Author(s)
      Jacob G, Shimomura K, Nakamura N
    • Total Pages
      9
    • Publisher
      Springer
    • Related Report
      2021 Research-status Report
  • [Book] ISAKOS/ICRS Book “Early Osteoarthritis” Chapter 15: The Current Role of Stem Cell Therapy and iPS Cells.2021

    • Author(s)
      Jacob G, Shimomura K, Hart DA, Nakamura N.
    • Total Pages
      13
    • Publisher
      Springer
    • Related Report
      2021 Research-status Report
  • [Book] ISAKOS/ICRS Book “Early Osteoarthritis” Chapter 19: Meniscus Injury and Early Osteoarthritis.2021

    • Author(s)
      Jacob G, Shimomura K, Hart DA, Nakamura N
    • Total Pages
      11
    • Publisher
      Springer
    • Related Report
      2021 Research-status Report
  • [Book] ISAKOS Book “Orthopaedic Biomechanics in Sports Medicine” Chapter 5:Mechanical and Biologic Properties of Articular Cartilage Repair Biomaterials.2021

    • Author(s)
      Jacob G, Shimomura K, Hart DA, Fujie H, Nakamura N
    • Total Pages
      15
    • Publisher
      Springer
    • Related Report
      2021 Research-status Report
  • [Book] ISAKOS Book “Orthopaedic Biomechanics in Sports Medicine” Chapter 33:Biomechanics of Cartilage Repair.2021

    • Author(s)
      Iseki T, Rothrauff BB, Shimomura K, Nakamura N
    • Total Pages
      8
    • Publisher
      Springer
    • Related Report
      2021 Research-status Report
  • [Book] ISAKOS Book “Joint Function Preservation” Chapter 20: Biphasic Osteochondral Restoration Techniques Using Synovial Stem Cells and Artificial Bone.2021

    • Author(s)
      Jacob G, Shimomura K, Ando W, Hart DA, Nakamura N
    • Total Pages
      7
    • Publisher
      Springer
    • Related Report
      2021 Research-status Report
  • [Book] ISAKOS Book “Advances in Knee Ligament and Knee Preservation Surgery” Chapter 35: Clinical Application of Scaffold-Free Tissue-Engineered Construct Derived from Synovial Stem Cells.2021

    • Author(s)
      Shimomura K, Hart DA, Ando W, Nakamura N
    • Total Pages
      9
    • Publisher
      Springer
    • Related Report
      2021 Research-status Report
  • [Book] ISAKOS Book “Advances in Knee Ligament and Knee Preservation Surgery” Chapter 37: Current Introduction of the Biological Agent Derived from Adipose Tissue to the Treatment of Knee Osteoarthritis.2021

    • Author(s)
      Ando W, Wolfe I, Shimomura K, Lyman S, Yokota N, Nakamura N
    • Total Pages
      14
    • Publisher
      Springer
    • Related Report
      2021 Research-status Report
  • [Book] ISAKOS/ICRS Book “Orthobiologics: Injectable Therapies for the Musculoskeletal System” Chapter 22: Meniscal Lesions: Cell Therapy.2021

    • Author(s)
      Shimomura K, Hart DA, Nakamura N
    • Total Pages
      12
    • Publisher
      Springer
    • Related Report
      2021 Research-status Report
  • [Book] ISAKOS/ICRS Book “Orthobiologics: Injectable Therapies for the Musculoskeletal System” Chapter 25: Cartilage Lesions and Osteoarthritis: Cell Therapy.2021

    • Author(s)
      Fernandes TL, Shimomura K, Hart DA, Boffa A, Nakamura N
    • Total Pages
      14
    • Publisher
      Springer
    • Related Report
      2021 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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