Skip to main content
SpringerLink
Log in

Biphasic Osteochondral Restoration Techniques Using Synovial Stem Cells and Artificial Bone

  • Chapter
  • First Online:
Joint Function Preservation

  • 1067 Accesses

Abstract

Synovial-derived mesenchymal stem cells (SDMSCs) have been shown to have superior proliferative and differentiation capacity when compared to other cell sources. A new tissue-engineered construct (TEC) has been developed using SDMSCs which is natural and scaffold-free. Early results of TEC in chondral repair strategies have been encouraging; demonstrating superior chondral repair in both preclinical and clinical trials. Beyond chondral repair, the next major clinical challenge is osteochondral lesions. Artificial bone implants such as hydroxyapatite and beta-tricalcium phosphate have been utilized in clinical settings for a significant amount of time and show good bone integrative properties. For this reason, TEC has been attached to artificial bone substitutes to create a biphasic implant that can address both the chondral and subchondral components of an osteochondral lesion. In this chapter, we describe the preclinical results employing TEC with artificial bone as a biphasic implant to address osteochondral lesions.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Gomoll AH, Madry H, Knutsen G, van Dijk N, Seil R, Brittberg M, et al. The subchondral bone in articular cartilage repair: current problems in the surgical management. Knee Surg Sport Traumatol Arthrosc. 2010;18(4):434–47.

    Article  Google Scholar 

  2. Gorbachova T, Melenevsky Y, Cohen M, Cerniglia BW. Osteochondral lesions of the knee: differentiating the most common entities at MRI. Radiographics. 2018;38(5):1478–95.

    Article  PubMed  Google Scholar 

  3. Willers C, Wood DJ, Zheng MH. A current review on the biology and treatment of articular cartilage defects (Part I & Part II). J Musculoskelet Res. 2003;7:157–81.

    Article  Google Scholar 

  4. Sakaguchi Y, Sekiya I, Yagishita K, Muneta T. Comparison of human stem cells derived from various mesenchymal tissues: superiority of synovium as a cell source. Arthritis Rheum. 2005;52:2521–9.

    Article  PubMed  Google Scholar 

  5. Mochizuki T, Muneta T, Sakaguchi Y, Nimura A, Yokoyama A, Koga H, et al. Higher chondrogenic potential of fibrous synovium- and adipose synovium-derived cells compared with subcutaneous fat-derived cells: distinguishing properties of mesenchymal stem cells in humans. Arthritis Rheum. 2006;54(3):843–53.

    Article  PubMed  CAS  Google Scholar 

  6. Fan J, Varshney RR, Ren L, Cai D, Wang DA. Synovium-derived mesenchymal stem cells: a new cell source for musculoskeletal regeneration. Tissue Eng B Rev. 2009;15:75–86.

    Article  CAS  Google Scholar 

  7. Shirasawa S, Sekiya I, Sakaguchi Y, Yagishita K, Ichinose S, Muneta T. In vitro chondrogenesis of human synovium-derived mesenchymal stem cells: optimal condition and comparison with bone marrow-derived cells. J Cell Biochem. 2006;97(1):84–97.

    Article  PubMed  CAS  Google Scholar 

  8. Fernandes TL, Kimura HA, Pinheiro CCG, Shimomura K, Nakamura N, Ferreira JR, et al. Human synovial mesenchymal stem cells good manufacturing practices for articular cartilage regeneration. Tissue Eng C Methods. 2018;24(12):709–16.

    Article  Google Scholar 

  9. De Bari C, Dell’Accio F, Tylzanowski P, Luyten FP. Multipotent mesenchymal stem cells from adult human synovial membrane. Arthritis Rheum. 2001;44:1928–42.

    Article  PubMed  Google Scholar 

  10. Koizumi K, Ebina K, Hart DA, Hirao M, Noguchi T, Sugita N, et al. Synovial mesenchymal stem cells from osteo- or rheumatoid arthritis joints exhibit good potential for cartilage repair using a scaffold-free tissue engineering approach. Osteoarthr Cartil. 2016;24(8):1413–22.

    Article  CAS  Google Scholar 

  11. Ando W, Tateishi K, Katakai D, Hart DA, Higuchi C, Nakata K, et al. In vitro generation of a scaffold-free tissue-engineered construct (TEC) derived from human synovial mesenchymal stem cells: biological and mechanical properties and further chondrogenic potential. Tissue Eng A. 2008;14(12):2041–9.

    Article  CAS  Google Scholar 

  12. Ando W, Tateishi K, Hart DA, Katakai D, Tanaka Y, Nakata K, et al. Cartilage repair using an in vitro generated scaffold-free tissue-engineered construct derived from porcine synovial mesenchymal stem cells. Biomaterials. 2007;28(36):5462–70.

    Article  PubMed  CAS  Google Scholar 

  13. Yasui Y, Ando W, Shimomura K, Koizumi K, Ryota C, Hamamoto S, et al. Scaffold-free, stem cell-based cartilage repair. J Clin Orthop Trauma. 2016;7:157–63.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Schnabel M, Marlovits S, Eckhoff G, Fichtel I, Gotzen L, Vécsei V, et al. Dedifferentiation-associated changes in morphology and gene expression in primary human articular chondrocytes in cell culture. Osteoarthr Cartil. 2002;10(1):62–70.

    Article  CAS  Google Scholar 

  15. Darling EM, Athanasiou KA. Rapid phenotypic changes in passaged articular chondrocyte subpopulations. J Orthop Res. 2005;23(2):425–32.

    Article  PubMed  CAS  Google Scholar 

  16. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4):663–76.

    Article  CAS  Google Scholar 

  17. Duan L, Ma B, Liang Y, Chen J, Zhu W, Li M, et al. Cytokine networking of chondrocyte dedifferentiation in vitro and its implications for cell-based cartilage therapy. Am J Transl Res. 2015;7:194–208.

    PubMed  PubMed Central  Google Scholar 

  18. Takahashi T, Ogasawara T, Asawa Y, Mori Y, Uchinuma E, Takato T, et al. Three-dimensional microenvironments retain chondrocyte phenotypes during proliferation culture. Tissue Eng. 2007;13(7):1583–92.

    Article  PubMed  CAS  Google Scholar 

  19. Shimomura K, Yasui Y, Koizumi K, Chijimatsu R, Hart DA, Yonetani Y, et al. First-in-human pilot study of implantation of a scaffold-free tissue-engineered construct generated from autologous synovial mesenchymal stem cells for repair of knee chondral lesions. Am J Sports Med. 2018;46(10):2384–93.

    Article  PubMed  Google Scholar 

  20. Shimomura K, Ando W, Moriguchi Y, Sugita N, Yasui Y, Koizumi K, et al. Next generation mesenchymal stem cell (MSC)–based cartilage repair using scaffold-free tissue engineered constructs generated with synovial mesenchymal stem cells. Cartilage. 2015;6:13–29.

    Article  Google Scholar 

  21. Kon E, Delcogliano M, Filardo G, Busacca M, Di Martino A, Marcacci M. Novel nano-composite multilayered biomaterial for osteochondral regeneration: a pilot clinical trial. Am J Sports Med. 2011;39(6):1180–90.

    Article  PubMed  Google Scholar 

  22. Shimomura K, Moriguchi Y, Murawski CD, Yoshikawa H, Nakamura N. Osteochondral tissue engineering with biphasic scaffold: current strategies and techniques. Tissue Eng B Rev. 2014;20:468–76.

    Article  CAS  Google Scholar 

  23. Ahn JH, Lee TH, Oh JS, Kim SY, Kim HJ, Park IK, et al. Novel hyaluronate-atelocollagen/beta-TCP-hydroxyapatite biphasic scaffold for the repair of osteochondral defects in rabbits. Tissue Eng Part A. 2009;15(9):2595–604.

    Article  PubMed  CAS  Google Scholar 

  24. Hung CT, Lima EG, Mauck RL, Taki E, LeRoux MA, Lu HH, et al. Anatomically shaped osteochondral constructs for articular cartilage repair. J Biomech. 2003;36(12):1853–64.

    Article  PubMed  Google Scholar 

  25. Alhadlaq A, Mao JJ. Tissue-engineered osteochondral constructs in the shape of an articular condyle. J Bone Joint Surg Am. 2005;87(5):936–44.

    Article  PubMed  Google Scholar 

  26. Kon E, Filardo G, Perdisa F, Venieri G, Marcacci M. Clinical results of multilayered biomaterials for osteochondral regeneration. J Exp Orthop. 2014;1(1):10.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Filardo G, Kon E, Di Martino A, Busacca M, Altadonna G, Marcacci M. Treatment of knee osteochondritis dissecans with a cell-free biomimetic osteochondral scaffold: clinical and imaging evaluation at 2-year follow-up. Am J Sports Med. 2013;41(8):1786–93.

    Article  PubMed  Google Scholar 

  28. Kon E, Filardo G, Di Martino A, Busacca M, Moio A, Perdisa F, et al. Clinical results and MRI evolution of a nano-composite multilayered biomaterial for osteochondral regeneration at 5 years. Am J Sports Med. 2014;42(1):158–65.

    Article  PubMed  Google Scholar 

  29. Delcogliano M, de Caro F, Scaravella E, Ziveri G, De Biase CF, Marotta D, et al. Use of innovative biomimetic scaffold in the treatment for large osteochondral lesions of the knee. Knee Surg Sport Traumatol Arthrosc. 2014;22(6):1260–9.

    Google Scholar 

  30. Brix M, Kaipel M, Kellner R, Schreiner M, Apprich S, Boszotta H, et al. Successful osteoconduction but limited cartilage tissue quality following osteochondral repair by a cell-free multilayered nano-composite scaffold at the knee. Int Orthop. 2016;40:625–32.

    Article  PubMed  Google Scholar 

  31. Di Martino A, Kon E, Perdisa F, Sessa A, Filardo G, Neri MP, et al. Surgical treatment of early knee osteoarthritis with a cell-free osteochondral scaffold: results at 24 months of follow-up. Injury. 2015;46 Suppl 8:S33–8.

    Article  PubMed  Google Scholar 

  32. Carmont MR, Carey-Smith R, Saithna A, Dhillon M, Thompson P, Spalding T. Delayed incorporation of a TruFit plug: perseverance is recommended. Arthroscopy. 2009;25:810–4.

    Article  PubMed  Google Scholar 

  33. Bedi A, Foo LF, Williams RJ, Potter HG. The maturation of synthetic scaffolds for osteochondral donor sites of the knee: an MRI and T2-mapping analysis. Cartilage. 2010;1:20–8.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Bugelli G, Ascione F, Dell’Osso G, Zampa V, Giannotti S. Biphasic bioresorbable scaffold (TruFit®) in knee osteochondral defects: 3-T MRI evaluation of osteointegration in patients with a 5-year minimum follow-up. Musculoskelet Surg. 2018;102:191–9.

    Article  PubMed  CAS  Google Scholar 

  35. Joshi N, Reverte-Vinaixa M, Díaz-Ferreiro EW, Domínguez-Oronoz R. Synthetic resorbable scaffolds for the treatment of isolated patellofemoral cartilage defects in young patients: magnetic resonance imaging and clinical evaluation. Am J Sports Med. 2012;40(6):1289–95.

    Article  PubMed  Google Scholar 

  36. Dhollander AAM, Liekens K, Almqvist KF, Verdonk R, Lambrecht S, Elewaut D, et al. A pilot study of the use of an osteochondral scaffold plug for cartilage repair in the knee and how to deal with early clinical failures. Arthroscopy. 2012;28(2):225–33.

    Article  PubMed  Google Scholar 

  37. Barber FA, Dockery WD. A computed tomography scan assessment of synthetic multiphase polymer scaffolds used for osteochondral defect repair. Arthroscopy. 2011;27(1):60–4.

    Article  PubMed  Google Scholar 

  38. Verhaegen J, Clockaerts S, Van Osch GJVM, Somville J, Verdonk P, Mertens P. TruFit plug for repair of osteochondral defects—where is the evidence? Systematic review of literature. Cartilage. 2015;6:12–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Kon E, Robinson D, Verdonk P, Drobnic M, Patrascu JM, Dulic O, et al. A novel aragonite-based scaffold for osteochondral regeneration: early experience on human implants and technical developments. Injury. 2016;47 Suppl 6:S27–32.

    Article  PubMed  Google Scholar 

  40. A DMB. Aragonite-based scaffold for the treatment of knee osteochondral defects: results of a prospective multi-center trial at 2 years’ follow-up. Bologna University; 2019.

    Google Scholar 

  41. Shimomura K, Moriguchi Y, Ando W, Nansai R, Fujie H, Hart DA, et al. Osteochondral repair using a scaffold-free tissue-engineered construct derived from synovial mesenchymal stem cells and a hydroxyapatite-based artificial bone. Tissue Eng A. 2014;20(17–18):2291–304.

    Article  CAS  Google Scholar 

  42. Gleeson JP, Plunkett NA, O’Brien FJ. Addition of hydroxyapatite improves stiffness, interconnectivity and osteogenic potential of a highly porous collagen-based scaffold for bone tissue regeneration. Eur Cells Mater. 2010;20:218–30.

    Article  CAS  Google Scholar 

  43. Shen C, Ma J, Chen XD, Dai LY. The use of β-TCP in the surgical treatment of tibial plateau fractures. Knee Surg Sport Traumatol Arthrosc. 2009;17(12):1406–11.

    Article  Google Scholar 

  44. Tamai N, Myoui A, Tomita T, Nakase T, Tanaka J, Ochi T, et al. Novel hydroxyapatite ceramics with an interconnective porous structure exhibit superior osteoconduction in vivo. J Biomed Mater Res. 2002;59(1):110–7.

    Article  PubMed  CAS  Google Scholar 

  45. Yamasaki N, Hirao M, Nanno K, Sugiyasu K, Tamai N, Hashimoto N, et al. A comparative assessment of synthetic ceramic bone substitutes with different composition and microstructure in rabbit femoral condyle model. J Biomed Mater Res B Appl Biomater. 2009;91(2):788–98.

    Article  PubMed  Google Scholar 

  46. Shimomura K, Moriguchi Y, Nansai R, Fujie H, Ando W, Horibe S, et al. Comparison of 2 different formulations of artificial bone for a hybrid implant with a tissue-engineered construct derived from synovial mesenchymal stem cells. Am J Sports Med. 2017;45(3):666–75.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan

    George Jacob, Kazunori Shimomura & Wataru Ando

  2. McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, AB, Canada

    David A. Hart

  3. Institute for Medical Science in Sports, Osaka Health Science University, Osaka, Japan

    Norimasa Nakamura

  4. Global Centre for Medical Engineering and Informatics, Osaka University, Osaka, Japan

    Norimasa Nakamura

Authors
  1. George Jacob
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kazunori Shimomura
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wataru Ando
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. David A. Hart
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Norimasa Nakamura
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Norimasa Nakamura .

Editor information

Editors and Affiliations

  1. O.A.S.I. Bioresearch Foundation Gobbi NPO, Milan, Italy

    Alberto Gobbi

  2. Musculoskeletal and Joint Research Foundation, San Diego, CA, USA

    John G. Lane

  3. Orthopaedics and Traumatology Unit, University Campus Biomedico, Roma, Italy

    Umile Giuseppe Longo

  4. OASI Bioresearch Foundation Gobbi NPO, Milan, Italy

    Ignacio Dallo

Rights and permissions

Reprints and permissions

Copyright information

© 2022 ISAKOS

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Jacob, G., Shimomura, K., Ando, W., Hart, D.A., Nakamura, N. (2022). Biphasic Osteochondral Restoration Techniques Using Synovial Stem Cells and Artificial Bone. In: Gobbi, A., Lane, J.G., Longo, U.G., Dallo, I. (eds) Joint Function Preservation. Springer, Cham. https://doi.org/10.1007/978-3-030-82958-2_20

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-82958-2_20

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-82957-5

  • Online ISBN: 978-3-030-82958-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation