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Scaffold-Free Endogenous Healing of the Articular Cartilage Lesion

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Sports Injuries

Abstract

The regeneration of the joint cartilage remains a major challenge in medicine, because the factors initiating cartilage formation, maturation, and healing are poorly understood. The ideal outcome of the joint cartilage repair is a restoration of columnar architecture and composition of articular joint hyaline cartilage. The field of tissue engineering (TE) has emerged over the past decades to improve the treatments for tissue and organ failure. TE can be broadly defined as a structural and functional reconstitution of mammalian tissues where the cells, biomaterials, and biological cues are combined. The development of a construct without an artificial scaffold is one of the main concepts of TE technology. A novel tissue-engineering technique has been recently developed for cartilage repair using a scaffold-free tissue-engineered construct (TEC) biosynthesized from allogeneic synovial MSCs.

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References

  • Ando W, Tateishi K, Hart DA, Katakai D, Tanaka Y, Nakata K, Hashimoto J, Fujie H, Shino K, Yoshikawa H, Nakamura N (2007) Cartilage repair using an in vitro generated scaffold-free tissue-engineered construct derived from porcine synovial mesenchymal stem cells. Biomaterials 28:5462–5470

    Article  PubMed  CAS  Google Scholar 

  • Ando W, Tateishi K, Katakai D, Hart DA, Higuchi C, Nakata K, Hashimoto J, Fujie H, Shino K, Yoshikawa H, Nakamura N (2008) 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 Part A 14:2041–2049

    Article  PubMed  CAS  Google Scholar 

  • Archer CW, Dowthwaite GP, Francis-West P (2003) Development of synovial joints. Birth Defects Res C Embryo Today 69:144–155

    Article  PubMed  CAS  Google Scholar 

  • Benthien JP, Behrens P (2011) The treatment of chondral and osteochondral defects of the knee with autologous matri-induced chondrogenesis (AMIC): method description and recent developments. Knee Surg Sports Traumatol Arthrosc 19:1316–1319

    Article  PubMed  Google Scholar 

  • Benya PD, Schaffer JD (1982) Dedifferentiated chondrocytes reexpress the differentiated collagen phenotype when cultured in agarose gel. Cell 30:215–224

    Article  PubMed  CAS  Google Scholar 

  • Brehm W, Aklin B, Yamashita T, Reiser F, Trub T, Jakob RP, Mainil-Varlet P (2006) Repair of superficial osteochondral defects with an autologous scaffold-free cartilage construct in a caprine model: implantation method and short-term results. Osteochondr Cart 14:1214–1226

    Article  CAS  Google Scholar 

  • Brucker PU, Braun S, Imhoff AB (2008) Mega-OATS technique-autologous osteochondral transplantation as a salvage procedure for large osteochondral defects of the femoral condyle. Oper Orthop Traumatol 20:188–198

    Article  PubMed  Google Scholar 

  • Carney EF (2012) Regenerative medicine: adipose stem cells fail to boost cartilage repair in rats. Nat Rev Rheumatol 8:563

    Article  PubMed  Google Scholar 

  • Chen WC, Yao CL, Wei YH, Chu IM (2011) Evaluating osteochondral defect repair potential of autologous rabbit bone marrow cells on type II collagen scaffold. Cytotechnology 63:13–23

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cucchiarini M, Madry H (2010) Genetic modification of mesenchymal stem cells for cartilage repair. Biomed Mater Eng 20:135–143

    PubMed  Google Scholar 

  • De Bari C, DellAccio F, Tylzanowski P, Luyten FP (2001) Multipotent mesenchymal stem cells from adult human synovial membrane. Arthritis Rheum 44:1928–1942

    Article  PubMed  Google Scholar 

  • Dominici H, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop DJ, Horwitz E (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315–317

    Article  PubMed  CAS  Google Scholar 

  • Domm C, Schunke M, Christensen K, Kurz B (2002) Redifferentiation of dedifferentiated bovine articular chondrocytes in alginate culture under low oxygen tension. Osteoarthr Cart 10:13–22

    Article  CAS  Google Scholar 

  • Elloumi-Hannacchi I, Yamato M, Okano T (2010) Cell sheet engineering: a unique nanotechnology for scaffold-free tissue reconstruction with clinical applications in regenerative medicine. J Intern Med 267:54–70

    Article  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Filardo G, Madry H, Jelic M, Roffi A, Cucchiarini M, Kon E (2013) Mesenchymal stem cells for the treatment of cartilage lesions: from preclinical findings to clinical application in orthopaedics. Knee Surg Sports Traumatol Arthrosc 21:1717–1729

    Article  PubMed  Google Scholar 

  • Firestein GS (1996) Invasive fibroblast-like synoviocytes in rheumatoid arthritis. Passive responders of transformed aggressors? Arthritis Rheum 39:1781–1790

    Article  PubMed  CAS  Google Scholar 

  • Flannery CR, Hughes CE, Schumacher BL, Tudor D, Aydelotte MB, Kuettner KE, Caterson B (1999) Biochem Biophys Res Commun 254:535–541

    Article  PubMed  CAS  Google Scholar 

  • Furukawa S, Suenaga H, Toita K, Numata A, Tanaka J, Ushida T, Sakai Y, Tateishi T (2003) Rapid and large scale formation of chondrocyte aggregates by rotational culture. Cell Transplant 12:475–479

    Article  PubMed  Google Scholar 

  • Furukawa KS, Imura K, Tateishi T, Ushida T (2008) Scaffold-free cartilage by rotational culture for tissue engineering. J Biotechnol 133:134–145

    Article  PubMed  CAS  Google Scholar 

  • Gobbi A, Karnatzikos G, Kumar A (2013) Long-term results after microfracture treatment for full-thickness knee chondral lesions in athletes. Knee Surg Sports Traumatol Arthrosc Epub ahead of print

    Google Scholar 

  • Gobbi A, Karnatzikos G, Sankineani SR (2014) One-step surgery with multipotent stem cells for the treatment of large full-thickness chondral defects of the nnee. Am J Sports Med 42:648–57

    Google Scholar 

  • Grogan SP, Rieser F, Winkelmann V, Berardi S, Mainil-Varlet P (2003) A static, closed and scaffold-free bioreactor system that permits chondrogenesis in vitro. Osteoarthr Cart 11:403–411

    Article  CAS  Google Scholar 

  • Hunziker EB, Rosenberg LC (1996) Repair of partial-thickness defects in articular cartilage: cell recruitment from the synovial membrane. J Bone Joint Surg Am 78:721–733

    PubMed  CAS  Google Scholar 

  • Jakob M, Demartean O, Schafer D, Hintermann B, Dick W, Heberer M, Martin I (2001) Specific growth factors during the expansion and redifferentiation of adult human articular chondrocytes enhance chondrogenesis and cartilaginous tissue formation in vitro. J Cell Biochem 81:368–377

    Article  PubMed  CAS  Google Scholar 

  • Jelic M, Pecina M, Haspl M, Kos J, Taylor K, Maticic D, McCartney J, Yis S, Rueger D, Vukicevic S (2001) Regeneration of articular cartilage chondral defects by osteogenic protein-1 (bone morphogenetic protein-7) in sheep. Growth Factors 19:101–113

    Article  PubMed  CAS  Google Scholar 

  • Jiabing F, Varshney RR, Daozhang C, Dong-An W (2009) Synovium-derived mesenchymal stem cells: a new cell source for musculoskeletal regeneration. Tissue Eng Part B Rev 15:75–86

    Google Scholar 

  • Jones E, McGonagle D (2011) Synovial mesenchymal stem cells in vivo. Potential key players for joint regeneration. World J Rheumatol 1:4–11

    Article  Google Scholar 

  • Jones BA, Pei M (2012) Synovium-derived stem cells: a tissue-specific stem cell for cartilage engineering and regeneration. Tissue Eng Part B Rev 18:301–311

    Article  PubMed  CAS  Google Scholar 

  • Katakai D, Imura M, Ando W, Tateishi K, Yoshikawa H, Nakamura N, Fujie H (2009) Compressive properties of cartilage-like tissues repaired in vivo with scaffold-free, tissue engineered constructs. Clin Biomech (Bristol, Avon) 24:110–116

    Article  CAS  Google Scholar 

  • Kelm JM, Fussenegger M (2004) Microscale tissue engineering using gravity-enforced cell assembly. Trends Biotechnol 22:195–202

    Article  PubMed  CAS  Google Scholar 

  • Kelm JM, Djonov V, Ittner LM, Fluri D, Born W, Hoerstrup SP, Fussenegger M (2006) Design of custom-shaped vascularized tissues using microtissue spheroids as minimal building units. Tissue Eng 12:2151–2160

    Article  PubMed  Google Scholar 

  • Kim HJ, Im GI (2009) Chondrogenic differentiation of adipose tissue-derived mesenchymal stem cells: greater doses of growth factor are necessary. J Orthop Res 27:612–619

    Article  PubMed  CAS  Google Scholar 

  • Kim HJ, Lee JH, Im G (2010) Chondrogenesis using mesenchymal stem cells and PCL scaffolds. J Biomed Mater Res A 92:659–666

    PubMed  Google Scholar 

  • Klein TJ, Sali RL (2007) Modulation of depth-dependent properties in tissue-engineered cartilage with a semi-permeable membrane and perfusion: a continuum model of matrix metabolism and transport. Biomech Model Mechanobiol 6:21–32

    Article  PubMed  CAS  Google Scholar 

  • Kreuz PC, Muller S, Ossendorf C, Kaps C, Erggelet C (2009) Treatment of focal degenerative cartilage defects with polymer-based autologous chondrocyte grafts: four-year clinical results. Arthritis Res Ther 11:R33

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kwon OH, Nho YC, Lee YM (2000) Radiation-induced grafting of methylmetacrylate onto ultrahigh molecular weight polyethylene and its adhesive characteristics. J Mater Sci Mater Med 11:593–600

    Article  PubMed  CAS  Google Scholar 

  • Lee CR, Grodzinsky AJ, Spector M (2003) Biosynthetic response of passaged chondrocytes in a type II collagen scaffold to mechanical compression. J Biomed Mater Res A 64:560–569

    Article  PubMed  CAS  Google Scholar 

  • Lee JI, Sato M, Kim HW, Mochida J (2011) Transplantation of scaffold-free spheroids composed of synovium-derived cells and chondrocytes for the treatment of cartilage defects of the knee. Eur Cell Mater 22:275–290

    PubMed  CAS  Google Scholar 

  • Lodi D, Iannitti T, Palmieri B (2011) Stem cells in clinical practice: applications and warnings. J Exp Clin Cancer Res 30:9

    Article  PubMed  PubMed Central  Google Scholar 

  • Mainil-Varlet P, Rieser F, Grogan S, Muller W, Saager C, Jakob RP (2001) Articular cartilage repair using a tissue-engineered cartilage-like implants an animal study. Osteoarthr Cart 9(Suppl A):S6–S15

    Article  Google Scholar 

  • Marlovits S, Tichy B, Truppe M, Gruber D, Vecsei V (2003) Chondrogenesis of aged human articular cartilage in a scaffold-free bioreactor. Tissue Eng 9:1215–1226

    Article  PubMed  CAS  Google Scholar 

  • Matsuda T, Magoshi T (2002) Preparation of vinylated polysaccharides and photo fabrication of tubular scaffolds as potential use in tissue engineering. Biomacromolecules 3:942–950

    Article  PubMed  CAS  Google Scholar 

  • Mironov V, Visconti RP, Kasyanov V, Forgacs G, Drake CJ, Markwald RR (2009) Organ printing: tissue spheroids as building blocks. Biomaterials 30:2164–2174

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mochizuki T, Muneta T, Sakaguchi Y, Nimura A, Yokoyama A, Koga H, Sekiya I (2006) Higher chondrogenic potential of fibrous synovium and adipose synovium-derived cells compared with subcutaneous fat-derived cells: distinguishing properties of mesenchymal stem cells in human. Arthritis Rheum 54:843–853

    Article  PubMed  CAS  Google Scholar 

  • Munirah S, Samsudin OC, Chen HC, Salmah SH, Aminuddin BS, Ruszymah BH (2007) Articular cartilage restoration in load-bearing osteochondral defects by implantation of autologous chondrocyte-fibrin constructs: an experimental study in sheep. J Bone Joint Surg (Br) 89:1099–1109

    Article  CAS  Google Scholar 

  • Nagase T, Muneta T, Ju YJ, Hara K, Morito T, Koge H, Nimura A, Mochizuki T, Sekiya I (2008) Analysis of the chondrogenic potential of human synovial stem cells according to harvest site and culture parameters in knees with medial compartment osteoarthritis. Arthritis Rheum 58:1389–1398

    Article  PubMed  Google Scholar 

  • Nansai R, Suzuki T, Shimomura K, Ando W, Nakamura N, Fujie H (2011) Surface morphology and stiffness of cartilage-like tissue repaired with a scaffold-free tissue engineered construct. J Biom Sc Eng 6:40–48

    Article  Google Scholar 

  • Nesic D, Whiteside R, Brittberg M, Wendt D, Martin I, Mainil-Varlet P (2006) Cartilage tissue engineering for degenerative joint disease. Adv Drug Deliv Rev 58:300–322

    Article  PubMed  CAS  Google Scholar 

  • Newman AP (1998) Articular cartilage repair. Am J Sports Med 26:309–324

    PubMed  CAS  Google Scholar 

  • Nishimura K, Solchaga LA, Caplan AI, Yoo JU, Goldberg VM, Johnstone B (1999) Chondroprogenitor cells of synovial tissue. Artrhitis Rheum 42:2631–2637

    Article  CAS  Google Scholar 

  • Park K, Huang J, Azar F, Jin RL, Min BH, Han DK, Hasty K (2006) Scaffold-free, engineered porcine cartilage construct for cartilage defect repair – in vitro and in vivo study. Artif Organs 30:586–596

    Article  PubMed  CAS  Google Scholar 

  • Pujol JP, Chadjichristos C, Legendre F, Bauge C, Beauchef G, Andriamanalijaona R, Galera P, Boumediene K (2008) Interleukin-1 and transforming growth factor-beta 1 as crucial factors in osteoarthritic cartilage metabolism. Connect Tissue Res 49:293–297

    Article  PubMed  CAS  Google Scholar 

  • Rhee DK, Marcelino J, Baker M, Gong Y, Smits P, Lefebvre V, Jay GD, Stewart M, Wang H, Warman ML, Carpten JD (2005) The secreted glycoprotein lubricin protects cartilage surfaces and inhibits synovial cell overgrowth. J Clin Invest 115:622–631

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Rueger DC, Chubinskaya S (2004) Bone morphogenetic proteins in articular cartilage repair. In: Vukicevic S, Sampath TK (eds) Bone morphogenetic proteins: regeneration of bone and beyond, PIR series. Birkauser Verlag AG, Basel, pp 213–244

    Google Scholar 

  • Sakaguchi Y, Sekiya I, Yagishita K, Muneta T (2005) Comparison of human stem cells derived from various mesenchymal tissues: superiority of synovium as a cell source. Arthritis Rheum 52:2521–2529

    Article  PubMed  Google Scholar 

  • Saris DB, Vanlauwe J, Victor J, Haspl M, Bohnsack M, Fortems Y, Vandekerckhove B, Almqvist KF, Claes T, Handelberg F, Lagae K, von der Bauwhede J, Vandenneucher H, Yang KG, Jelic M, Verdonk K, Veulemans N, Bellemans J, Luyten FP (2008) Characterized chondrocyte implantation results in better structural repair when treating symptomatic cartilage defects of the knee in a randomized controlled trial versus microfracture. Am J Sports Med 36:235–246

    Article  PubMed  Google Scholar 

  • Schmidt MB, Chen EH, Lynch SE (2006) A review of the effects of insulin-like growth factor and platelet derived growth factor on in vivo cartilage healing and repair. Osteoarthr Cart 14:403–412

    Article  CAS  Google Scholar 

  • Stoddart MJ, Ettinger L, Hauselmann HJ (2006) Generation of a scaffold free cartilage-like implant from a small amount of starting material. J Cell Mol Med 10:480–492

    Article  PubMed  CAS  Google Scholar 

  • Theoret CL, Berber SM, Moyana T, Townsend HG, Archer JF (1996) Repair and function of the equine antebrachiocarpal joint. Vet Surg 25:142–153

    Article  PubMed  CAS  Google Scholar 

  • Tsuchiya K, Furukawa S, Ushida T (2006) Microelements for cartilage tissue engineering. Biomech Micro Nanoscale Levels 2:87–95

    Article  Google Scholar 

  • Tsuda Y, Shimizu T, Yamato M, Kikuchi A, Sasagawa T, Sekiya S, Kobayashi J, Chen G, Okano T (2007) Cellular control of tissue architectures using a three-dimensional tissue fabrication technique. Biomechanicals 28:4939–4946

    CAS  Google Scholar 

  • Ushida T, Furukawa K, Toita K, Tateishi T (2002) Three-dimensional seeding of chondrocytes encapsulated in collagen gel into PLLA scaffolds. Cell Transplant 11:489–494

    PubMed  Google Scholar 

  • Vanlauwe J, Saris DB, Victor J, Almqvist KF, Bellemans J, Luyten FP (2011) Five-year outcome of characterized chondrocyte implantation versus microfracture for symptomatic cartilage defects of the knee: early treatment matters. Am J Sports Med 39:2566–2574

    Article  PubMed  Google Scholar 

  • Venkatesan JK, Ekici M, Madry H, Schmitt G, Kohn D, Cucchiarini M (2012) SOX9 gene transfer via safe, stable, replication-defective recombinant adeno-associated virus vectors as a novel, powerful tool to enhance the chondrogenic potential of human mesenchymal stem cells. Stem Cell Res Ther 3:22

    Article  PubMed  PubMed Central  Google Scholar 

  • von der Mark K, Gauss V, von der Mark H, Muller P (1977) Relationship between cell shape and type of collagen synthesised as chondrocytes lose their cartilage phenotype in culture. Nature 267:531–532

    Article  PubMed  Google Scholar 

  • Waldman SD, Grynpas MD, Pilliar RM, Kandel RA (2002) Characterization of cartilaginous tissue formed on calcium phosphate substrates in vitro. J Biomed Mater Res 62:323–330

    Article  PubMed  CAS  Google Scholar 

  • Wang X, Grogan SP, Rieser F, Winkelmann V, Maquet V, Berge ML, Mainil-Varlet P (2004) Tissue engineering of biphasic cartilage constructs using various biodegradable scaffolds: an in vitro study. Biomaterials 25:3681–3688

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Clinical Hospital Center, School of Medicine, University of Zagreb, Salata 11, Zagreb, Croatia

    Mislav Jelic

  2. Laboratory for Mineralized Tissues, Center for Translational and Clinical Research, School of Medicine, University of Zagreb, Zagreb, Croatia

    Lovorka Grgurevic & Slobodan Vukicevic

  3. Department of Anatomy, School of Medicine, University of Zagreb, Å alata, Zagreb, Croatia

    Slobodan Vukicevic

Authors
  1. Mislav Jelic
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  2. Lovorka Grgurevic
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  3. Slobodan Vukicevic
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Correspondence to Mislav Jelic .

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Editors and Affiliations

  1. Dept. Orthopedics & Traumatology, Hacettepe University Fac. Medicine, Ankara, Turkey

    Mahmut Nedim Doral

  2. Gothenburg, Sweden

    Jon Karlsson

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Jelic, M., Grgurevic, L., Vukicevic, S. (2014). Scaffold-Free Endogenous Healing of the Articular Cartilage Lesion. In: Doral, M., Karlsson, J. (eds) Sports Injuries. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-36801-1_158-1

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  • DOI: https://doi.org/10.1007/978-3-642-36801-1_158-1

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