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Cartilage Tissue Engineering and Regenerative Strategies

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Regenerative Strategies for the Treatment of Knee Joint Disabilities

Part of the book series: Studies in Mechanobiology, Tissue Engineering and Biomaterials ((SMTEB,volume 21))

Abstract

Human adult articular cartilage is a unique avascular tissue which displays the ability to resist to repetitive compressive stress. However, this connective tissue exhibits slight capacity for intrinsic restoration and, then even injuries or lesions can lead to progressive damage and osteoarthritic joint deterioration. Therefore, the field of cartilage repair continues to expand, bridging the gap between palliative care and chondral defects reconstruction. Tissue engineering strategy, centered on three actors: cells, proteins and scaffolds, received a lot of attention in the aim to develop an articular cartilage regeneration process that will be efficient, simple, and based on global market, cost-effective. The current state of cartilage tissue engineering with respect to different cell-sources, growth factors and biomaterial scaffolds, as well as the strategies employed in the restoration and repair of damaged articular cartilage will be the focus of this book chapter.

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References

  1. Huey DJ, Hu JC, Athanasiou KA (2012) Unlike bone, cartilage regeneration remains elusive. Science 338:917–921. doi:10.1126/science.1222454

    Article  Google Scholar 

  2. Matsiko A, Levingstone T, O’Brien F (2013) Advanced strategies for articular cartilage defect repair. Materials (Basel) 6:637–668. doi:10.3390/ma6020637

    Article  Google Scholar 

  3. Moran CJ, Pascual-Garrido C, Chubinskaya S et al (2014) Restoration of articular cartilage. J Bone Joint Surg Am 96:336–344. doi:10.2106/JBJS.L.01329

    Article  Google Scholar 

  4. Johnstone B, Alini M, Cucchiarini M (2013) Tissue engineering for articular cartilage repair—the state of the art. Eur Cell Mater 25:248–267

    Google Scholar 

  5. Makris EA, Gomoll AH, Malizos KN et al (2014) Repair and tissue engineering techniques for articular cartilage. Nat Rev Rheumatol. doi:10.1038/nrrheum.2014.157

    Google Scholar 

  6. Wilusz RE, Sanchez-adams J, Guilak F (2014) The structure and function of the pericellular matrix of articular cartilage. Matrix Biol 39:25–32. doi:10.1016/j.matbio.2014.08.009

    Article  Google Scholar 

  7. Nukavarapu SP, Dorcemus DL (2013) Osteochondral tissue engineering: current strategies and challenges. Biotechnol Adv 31:706–721. doi:10.1016/j.biotechadv.2012.11.004

    Article  Google Scholar 

  8. Hsueh M, Önnerfjord P, Byers V (2014) Biomarkers and proteomic analysis of osteoarthritis. Matrix Biol 39:56–66. doi:10.1016/j.matbio.2014.08.012

    Article  Google Scholar 

  9. Dewan AK, Gibson MA, Elisseeff JH, Trice ME (2014) Evolution of autologous chondrocyte repair and comparison to other cartilage repair techniques. Biomed Res Int 2014:11. doi:10.1155/2014/272481

    Article  Google Scholar 

  10. Leyh M, Seitz A, Dürselen L et al (2014) Subchondral bone influences chondrogenic differentiation and collagen production of human bone marrow-derived mesenchymal stem cells and articular chondrocytes. Arthritis Res Ther 16:1–18. doi:10.1186/s13075-014-0453-9

    Article  Google Scholar 

  11. Hong E, Reddi AH (2013) Dedifferentiation and redifferentiation of articular chondrocytes from surface and middle zones: changes in microRNAs-221/-222, -140, and -143/145 expression. Tissue Eng Part A 19:1015–1022. doi:10.1089/ten.TEA.2012.0055

    Article  Google Scholar 

  12. Hubka KM, Dahlin RL, Meretoja VV et al (2014) Enhancing chondrogenic phenotype for cartilage tissue engineering: monoculture and coculture of articular chondrocytes and mesenchymal stem cells. Tissue Eng Part B Rev 20:641–654. doi:10.1089/ten.TEB.2014.0034

    Article  Google Scholar 

  13. Li S, Sengers BG, Oreffo RO, Tare RS (2015) Chondrogenic potential of human articular chondrocytes and skeletal stem cells: a comparative study. J Biomater Appl 29:824–836. doi:10.1177/0885328214548604

    Article  Google Scholar 

  14. Rosenzweig DH, Matmati M, Khayat G et al (2012) Culture of primary bovine chondrocytes on a continuously expanding surface inhibits dedifferentiation. Tissue Eng Part A 18:120803081750003. doi:10.1089/ten.tea.2012.0215

    Article  Google Scholar 

  15. Rosenzweig DH, Ou SJ, Quinn TM (2013) P38 mitogen-activated protein kinase promotes dedifferentiation of primary articular chondrocytes in monolayer culture. J Cell Mol Med 17:508–517. doi:10.1111/jcmm.12034

    Article  Google Scholar 

  16. Ma B, Leijten JCH, Wu L et al (2013) Gene expression profiling of dedifferentiated human articular chondrocytes in monolayer culture. Osteoarthr Cartil 21:599–603. doi:10.1016/j.joca.2013.01.014

    Article  Google Scholar 

  17. DuRaine GD, Brown WE, Hu JC, Athanasiou KA (2014) Emergence of scaffold-free approaches for tissue engineering musculoskeletal cartilages. Ann Biomed Eng. doi:10.1007/s10439-014-1161-y

    Google Scholar 

  18. Cucchiarini M, Venkatesan JK, Ekici M et al (2012) Human mesenchymal stem cells overexpressing therapeutic genes: from basic science to clinical applications for articular cartilage repair. Biomed Mater Eng 22:197–208. doi:10.3233/BME-2012-0709

    Google Scholar 

  19. Trappmann B, Gautrot JE, Connelly JT et al (2012) Extracellular-matrix tethering regulates stem-cell fate. Nat Mater 11:642–649. doi:10.1038/nmat3339

    Article  Google Scholar 

  20. Paschos NK, Brown WE, Eswaramoorthy R et al (2014) Advances in tissue engineering through stem cell-based co-culture. J Tissue Eng Regen Med 4:524–531. doi:10.1002/term.1870

    Google Scholar 

  21. Park H, Jung S, Yang K et al (2014) Biomaterials paper-based bioactive scaffolds for stem cell-mediated bone tissue engineering. Biomaterials 35:9811–9823. doi:10.1016/j.biomaterials.2014.09.002

    Article  Google Scholar 

  22. Chen W, Villa-Diaz LG, Sun Y et al (2012) Nanotopography influences adhesion, spreading, and self-renewal of human embryonic stem cells. ACS Nano 6:4094–4103. doi:10.1021/nn3004923

    Article  Google Scholar 

  23. Kamei K-I, Hirai Y, Yoshioka M et al (2013) Phenotypic and transcriptional modulation of human pluripotent stem cells induced by nano/microfabrication materials. Adv Healthc Mater 2:287–291. doi:10.1002/adhm.201200283

    Article  Google Scholar 

  24. Baghaban Eslaminejad M, Malakooty Poor E (2014) Mesenchymal stem cells as a potent cell source for articular cartilage regeneration. World J Stem Cells 6:344–354. doi:10.4252/wjsc.v6.i3.344

    Article  Google Scholar 

  25. Toh WS, Foldager CB, Pei M, Hui JHP (2014) Advances in mesenchymal stem cell-based strategies for cartilage repair and regeneration. Stem Cell Rev 10:686–696. doi:10.1007/s12015-014-9526-z

    Article  Google Scholar 

  26. Brown PT, Handorf AM, Jeon WB, Li W-J (2013) Stem cell-based tissue engineering approaches for musculoskeletal regeneration. Curr Pharm Des 19:3429–3445. doi:10.1016/j.biotechadv.2011.08.021.Secreted

    Article  Google Scholar 

  27. Fernández Vallone VB, Romaniuk MA, Choi H et al (2013) Mesenchymal stem cells and their use in therapy: what has been achieved? Differentiation 85:1–10. doi:10.1016/j.diff.2012.08.004

    Article  Google Scholar 

  28. Lee T, Jang J, Kang S et al (2014) Mesenchymal stem cell-conditioned medium enhances embryonic stem cells and human induced pluripotent stem cells by mesodermal lineage induction. Tissue Eng Part A 20:1306–1313. doi:10.1089/ten.tea.2013.0265

    Article  Google Scholar 

  29. Orth P, Rey-Rico A (2014) Current perspectives in stem cell research for knee cartilage repair. Stem Cells 7:1–17

    Google Scholar 

  30. Patel DM, Shah J, Srivastava AS (2013) Therapeutic potential of mesenchymal stem cells in regenerative medicine. Stem Cells Int. doi:10.1155/2013/496218

    Google Scholar 

  31. Ma S, Xie N, Li W et al (2014) Immunobiology of mesenchymal stem cells. Cell Death Differ 21:216–225. doi:10.1038/cdd.2013.158

    Article  Google Scholar 

  32. Wei X, Yang X, Han Z et al (2013) Mesenchymal stem cells: a new trend for cell therapy. Acta Pharmacol Sin 34:747–754. doi:10.1038/aps.2013.50

    Article  Google Scholar 

  33. Figueroa FE, Carrión F, Villanueva S, Khoury M (2012) Mesenchymal stem cell treatment for autoimmune diseases: a critical review. Biol Res 45:269–277. doi:10.4067/S0716-97602012000300008

    Article  Google Scholar 

  34. Kean TJ, Lin P, Caplan AI, Dennis JE (2013) MSCs: delivery routes and engraftment, cell-targeting strategies, and immune modulation. Stem Cells Int. doi:10.1155/2013/732742

    Google Scholar 

  35. Mabuchi Y, Houlihan DD, Akazawa C et al (2013) Prospective isolation of murine and human bone marrow mesenchymal stem cells based on surface markers. Stem Cells Int 2013:507301. doi:10.1155/2013/507301

    Article  Google Scholar 

  36. Wang S, Chang Q, Kong X, Wang C (2015) The chondrogenic induction potential for bone marrow-derived stem cells between autologous platelet-rich plasma and common chondrogenic induction agents: a preliminary comparative study. Stem Cells Int 2015:1–7, Article ID 589124. doi: 10.1155/2015/589124

  37. Torreggiani E, Lisignoli G, Manferdini C et al (2012) Role of slug transcription factor in human mesenchymal stem cells. J Cell Mol Med 16:740–751. doi:10.1111/j.1582-4934.2011.01352.x

    Article  Google Scholar 

  38. Bosetti M, Boccafoschi F, Leigheb M et al (2012) Chondrogenic induction of human mesenchymal stem cells using combined growth factors for cartilage tissue engineering. J Tissue Eng Regen Med 6:205–213. doi:10.1002/term.416

    Article  Google Scholar 

  39. Lynch K, Pei M (2014) Age associated communication between cells and matrix: a potential impact on stem cell-based tissue regeneration strategies. Organogenesis. doi:10.4161/15476278.2014.970089

    Google Scholar 

  40. Orbay H, Tobita M, Mizuno H (2012) Mesenchymal stem cells isolated from adipose and other tissues: basic biological properties and clinical applications. Stem Cells Int. doi:10.1155/2012/461718

    Google Scholar 

  41. Zuk P (2013) Adipose-derived stem cells in tissue regeneration: a review. ISRN Stem Cells 2013:1–35. doi:10.1155/2013/713959

    Article  Google Scholar 

  42. Li X, Yuan J, Li W et al (2014) Direct differentiation of homogeneous human adipose stem cells into functional hepatocytes by mimicking liver embryogenesis. J Cell Physiol 229:801–812. doi:10.1002/jcp.24501

    Article  Google Scholar 

  43. Sun H, Liu Y, Jiang T et al (2014) Chondrogenic differentiation and three dimensional chondrogenesis of human adipose-derived stem cells induced by engineered cartilage-derived conditional media. Tissue Eng Regen Med 11:59–66. doi:10.1007/s13770-013-1120-y

    Article  Google Scholar 

  44. De Sousa E, Casado PL, Neto VM et al (2014) Synovial fluid and synovial membrane mesenchymal stem cells: latest discoveries and therapeutic perspectives. Stem Cell Res Ther 5:1–6

    Article  Google Scholar 

  45. Gupta PK, Das AK, Chullikana A, Majumdar AS (2012) Mesenchymal stem cells for cartilage repair in osteoarthritis. Stem Cell Res Ther 3:25. doi:10.1186/scrt116

    Article  Google Scholar 

  46. Campbell D, Pei M (2012) Surface markers for chondrogenic determination: a highlight of synovium-derived stem cells. Cells 1:1107–1120. doi:10.3390/cells1041107

    Article  Google Scholar 

  47. Nakamura T, Sekiya I, Muneta T et al (2012) Arthroscopic, histological and MRI analyses of cartilage repair after a minimally invasive method of transplantation of allogeneic synovial mesenchymal stromal cells into cartilage defects in pigs. Cytotherapy 14:327–338. doi:10.3109/14653249.2011.638912

    Article  Google Scholar 

  48. Lee JC, Min HJ, Park HJ et al (2013) Synovial membrane-derived mesenchymal stem cells supported by platelet-rich plasma can repair osteochondral defects in a rabbit model. Arthrosc J Arthrosc Relat Surg 29:1034–1046. doi:10.1016/j.arthro.2013.02.026

    Article  Google Scholar 

  49. Lee J-C, Lee SY, Min HJ et al (2012) Synovium-derived mesenchymal stem cells encapsulated in a novel injectable gel can repair osteochondral defects in a rabbit model. Tissue Eng Part A 18:2173–2186. doi:10.1089/ten.tea.2011.0643

    Article  Google Scholar 

  50. Gong SP, Kim B, Kwon HS et al (2014) The co-injection of somatic cells with embryonic stem cells affects teratoma formation and the properties of teratoma-derived stem cell-like cells. PLoS ONE 9:1–9. doi:10.1371/journal.pone.0105975

    Google Scholar 

  51. Lee M-O, Moon SH, Jeong H-C et al (2013) Inhibition of pluripotent stem cell-derived teratoma formation by small molecules. Proc Natl Acad Sci USA 110:E3281–E3290. doi:10.1073/pnas.1303669110

    Article  Google Scholar 

  52. Cheng A, Kapacee Z, Peng J et al (2014) Cartilage repair using human embryonic stem cell-derived chondroprogenitors. Stem Cells Trans Med Publ 3:1–8. doi:10.5966/sctm.2014-0101

    Article  Google Scholar 

  53. Craft AM, Ahmed N, Rockel JS et al (2013) Specification of chondrocytes and cartilage tissues from embryonic stem cells. Development 140:2597–2610. doi:10.1242/dev.087890

    Article  Google Scholar 

  54. Tsumaki N, Okada M, Yamashita A (2014) IPS cell technologies and cartilage regeneration. Bone. doi:10.1016/j.bone.2014.07.011

    Google Scholar 

  55. Stromps J-P, Paul NE, Rath B et al (2014) Chondrogenic differentiation of human adipose-derived stem cells: a new path in articular cartilage defect management? Biomed Res Int 2014:740926. doi:10.1155/2014/740926

    Article  Google Scholar 

  56. Fisher MC (2012) The potential of human embryonic stem cells for articular cartilage repair and osteoarthritis treatment. Rheumatol Curr Res. doi:10.4172/2161-1149.S3-004

    Google Scholar 

  57. Diekman BO, Christoforou N, Willard VP et al (2012) Cartilage tissue engineering using differentiated and purified induced pluripotent stem cells. Proc Natl Acad Sci. doi:10.1073/pnas.1210422109

    Google Scholar 

  58. Irion VH, Flanigan DC (2013) New and emerging techniques in cartilage repair: other scaffold-based cartilage treatment options. Oper Tech Sports Med 21:125–137. doi:10.1053/j.otsm.2013.03.001

    Article  Google Scholar 

  59. Liu M, Yu X, Huang F et al (2013) Tissue engineering stratified scaffolds for articular cartilage and subchondral bone defects repair. Orthopedics 36:868–873. doi:10.3928/01477447-20131021-10

    Article  Google Scholar 

  60. Salgado AJ, Oliveira JM, Martins A et al (2013) Tissue engineering and regenerative medicine: past, present, and future. Int Rev Neurobiol. doi:10.1016/B978-0-12-410499-0.00001-0

    Google Scholar 

  61. Cao Z, Dou C, Dong S (2014) Scaffolding biomaterials for cartilage regeneration. J Nanomater 2014:1–8. doi:10.1155/2014/489128

    Article  Google Scholar 

  62. Rodrigues MT, Lee SJ, Gomes ME et al (2012) Bilayered constructs aimed at osteochondral strategies: the influence of medium supplements in the osteogenic and chondrogenic differentiation of amniotic fluid-derived stem cells. Acta Biomater 8:2795–2806. doi:10.1016/j.actbio.2012.04.013

    Article  Google Scholar 

  63. Izadifar Z, Chen X, Kulyk W (2012) Strategic design and fabrication of engineered scaffolds for articular cartilage repair. J Funct Biomater 3:799–838. doi:10.3390/jfb3040799

    Article  Google Scholar 

  64. Demoor M, Ollitrault D, Gomez-Leduc T et al (2014) Cartilage tissue engineering: molecular control of chondrocyte differentiation for proper cartilage matrix reconstruction. Biochim Biophys Acta 1840:2414–2440. doi:10.1016/j.bbagen.2014.02.030

    Article  Google Scholar 

  65. Zhang Z, Gupte M, Ma P (2013) Biomaterials and stem cells for tissue engineering. Expert Opin Biol 13:527–540. doi:10.1517/14712598.2013.756468.Biomaterials

    Article  Google Scholar 

  66. Griffin M, Butler P, Seifalian A, Szarko M (2013) Update into articular cartilage tissue engineering. OapublishinglondonCom 1:1–6

    Google Scholar 

  67. Musumeci G, Castrogiovanni P, Leonardi R et al (2014) New perspectives for articular cartilage repair treatment through tissue engineering: a contemporary review. World J Orthop 5:80–88. doi:10.5312/wjo.v5.i2.80

    Article  Google Scholar 

  68. Sun J, Tan H (2013) Alginate-based biomaterials for regenerative medicine applications. Materials (Basel) 6:1285–1309. doi:10.3390/ma6041285

    Article  Google Scholar 

  69. Goldman SM, Barabino GA (2014) Cultivation of agarose-based microfluidic hydrogel promotes the development of large, full-thickness, tissue-engineered articular cartilage constructs. J Tissue Eng Regen Med. doi:10.1002/term.1954

    Google Scholar 

  70. Martins EAN, Michelacci YM, Baccarin RYA et al (2014) Evaluation of chitosan-GP hydrogel biocompatibility in osteochondral defects: an experimental approach. BMC Vet Res 10:1

    Article  Google Scholar 

  71. Whu SW, Hung K-C, Hsieh K-H et al (2013) In vitro and in vivo evaluation of chitosan–gelatin scaffolds for cartilage tissue engineering. Mater Sci Eng C Mater Biol Appl 33:2855–2863. doi:10.1016/j.msec.2013.03.003

    Article  Google Scholar 

  72. Unterman SA, Gibson M, Lee JH et al (2012) Hyaluronic acid-binding scaffold for articular cartilage repair. Tissue Eng Part A 18:120814114305007. doi:10.1089/ten.tea.2011.0711

    Article  Google Scholar 

  73. Levett PA, Hutmacher DW, Malda J, Klein TJ (2014) Hyaluronic acid enhances the mechanical properties of tissue-engineered cartilage constructs. PLoS ONE 9:e113216. doi:10.1371/journal.pone.0113216

    Article  Google Scholar 

  74. Ahearne M, Kelly DJ (2013) A comparison of fibrin, agarose and gellan gum hydrogels as carriers of stem cells and growth factor delivery microspheres for cartilage regeneration. Biomed Mater 8:035004. doi:10.1088/1748-6041/8/3/035004

    Article  Google Scholar 

  75. Chung JY, Song M, Ha C-W et al (2014) Comparison of articular cartilage repair with different hydrogel-human umbilical cord blood-derived mesenchymal stem cell composites in a rat model. Stem Cell Res Ther 5:39. doi:10.1186/scrt427

    Article  Google Scholar 

  76. Mastbergen SC, Saris DB, Lafeber FP (2013) Functional articular cartilage repair: here, near, or is the best approach not yet clear? Nat Rev Rheumatol 9:277–290. doi:10.1038/nrrheum.2013.29

    Article  Google Scholar 

  77. Freymann U, Petersen W, Kaps C (2013) Cartilage regeneration revisited: entering of new one-step procedures for chondral cartilage repair. OapublishinglondonCom 1:1–6

    Google Scholar 

  78. Yodmuang S, Mcnamara SL, Nover AB et al (2014) Silk microfiber-reinforced silk hydrogel composites for functional cartilage tissue repair. Acta Biomater. doi:10.1016/j.actbio.2014.09.032

    Google Scholar 

  79. Snyder TN, Madhavan K, Intrator M et al (2014) A fibrin/hyaluronic acid hydrogel for the delivery of mesenchymal stem cells and potential for articular cartilage repair. J Biol Eng 8:10. doi:10.1186/1754-1611-8-10

    Article  Google Scholar 

  80. Pereira DR, Canadas RF, Silva-Correia J et al (2013) Gellan gum-based hydrogel bilayered scaffolds for osteochondral tissue engineering. Key Eng Mater 587:255–260. doi:10.4028/www.scientific.net/KEM.587.255

    Article  Google Scholar 

  81. Popa EG, Reis RL, Gomes ME (2014) Seaweed polysaccharide-based hydrogels used for the regeneration of articular cartilage. Crit Rev Biotechnol 8551:1–14. doi:10.3109/07388551.2014.889079

    Google Scholar 

  82. Sharma B, Fermanian S, Gibson M et al (2013) Human cartilage repair with a photoreactive adhesive-hydrogel composite. Sci Transl Med 5:167ra6. doi:10.1126/scitranslmed.3004838

    Article  Google Scholar 

  83. Norton AB, Hancocks RD, Grover LM (2014) Poly (vinyl alcohol) modification of low acyl gellan hydrogels for applications in tissue regeneration. Food Hydrocoll 42:373–377. doi:10.1016/j.foodhyd.2014.05.001

    Article  Google Scholar 

  84. Balakrishnan B, Joshi N, Banerjee R (2013) Borate aided Schiff’s base formation yields in situ gelling hydrogels for cartilage regeneration. J Mater Chem B 1:5564. doi:10.1039/c3tb21056a

    Article  Google Scholar 

  85. Chen J-L, Duan L, Zhu W et al (2014) Extracellular matrix production in vitro in cartilage tissue engineering. J Transl Med 12:88. doi:10.1186/1479-5876-12-88

    Article  Google Scholar 

  86. Nooeaid P, Salih V, Beier JP, Boccaccini AR (2012) Osteochondral tissue engineering: scaffolds, stem cells and applications. J Cell Mol Med 16:2247–2270. doi:10.1111/j.1582-4934.2012.01571.x

    Article  Google Scholar 

  87. Alves da Silva ML, Costa-Pinto AR, Martins A et al (2013) Conditioned medium as a strategy for human stem cells chondrogenic differentiation. J Tissue Eng Regen Med 4:524–531. doi:10.1002/term.1812

    Google Scholar 

  88. Fernandes-Silva S, Moreira-Silva J, Silva TH et al (2013) Porous hydrogels from shark skin collagen crosslinked under dense carbon dioxide atmosphere. Macromol Biosci 13:1621–1631. doi:10.1002/mabi.201300228

    Article  Google Scholar 

  89. Chen C-H, Shyu VB-H, Chen J-P, Lee M-Y (2014) Selective laser sintered poly-ε-caprolactone scaffold hybridized with collagen hydrogel for cartilage tissue engineering. Biofabrication 6:015004. doi:10.1088/1758-5082/6/1/015004

    Article  Google Scholar 

  90. Yan LP, Oliveira JM, Oliveira AL et al (2012) Macro/microporous silk fibroin scaffolds with potential for articular cartilage and meniscus tissue engineering applications. Acta Biomater 8:289–301. doi:10.1016/j.actbio.2011.09.037

    Article  Google Scholar 

  91. Yan L-P, Silva-Correia J, Oliveira MB et al (2015) Bilayered silk/silk-nanoCaP scaffolds for osteochondral tissue engineering: in vitro and in vivo assessment of biological performance. Acta Biomater. doi:10.1016/j.actbio.2014.10.021

    Google Scholar 

  92. Yan L, Oliveira JM, Oliveira AL, Reis RL (2014) In vitro evaluation of the biological performance of macro/micro-porous silk fibroin and silk-nano calcium phosphate scaffolds. J Biomed Mater Res Part B. doi:10.1002/jbm.b.33267

    Google Scholar 

  93. Ferris CJ, Stevens LR, Gilmore KJ et al (2014) Peptide modification of purified gellan gum. J Mater Chem B. doi:10.1039/c4tb01727g

    Google Scholar 

  94. Ferris CJ, Gilmore KJ, Wallace GG, Panhuis M et al (2013) Modified gellan gum hydrogels for tissue engineering applications. Soft Matter 9:3705. doi:10.1039/c3sm27389j

    Article  Google Scholar 

  95. Beachley V, Hepfer RG, Katsanevakis E et al (2014) Precisely assembled nanofiber arrays as a platform to engineer aligned cell sheets for biofabrication. Bioengineering 1:114–133. doi:10.3390/bioengineering1030114

    Article  Google Scholar 

  96. Bourget J, Guillemette M, Veres T et al (2013) Alignment of cells and extracellular matrix within tissue-engineered substitutes. Adv Biomater Sci Biomed Appl Ref. doi:10.5772/54142

    Google Scholar 

  97. Mashhadikhan M, Soleimani M, Parivar K, Yaghmaei P (2015) ADSCs on PLLA/PCL hybrid nanoscaffold and gelatin modification: cytocompatibility and mechanical properties. Avicenna J Med Biotechnol 7:32–38

    Google Scholar 

  98. Venugopal JR, Prabhakaran MP, Mukherjee S et al (2012) Biomaterial strategies for alleviation of myocardial infarction. J R Soc Interface 9:1–19. doi:10.1098/rsif.2011.0301

    Article  Google Scholar 

  99. Markeson D, Pleat JM, Sharpe JR et al (2013) Scarring, stem cells, scaffolds and skin repair. J Tissue Eng Regen Med 4:524–531. doi:10.1002/term.1841

    Google Scholar 

  100. Zeng W, Rong M, Hu X et al (2014) Incorporation of chitosan microspheres into collagen–chitosan scaffolds for the controlled release of nerve growth factor. PLoS ONE. doi:10.1371/journal.pone.0101300

    Google Scholar 

  101. Thomopoulos S, Sakiyama-Elbert S, Silva M et al (2014) Polymer nanofiber scaffold for a heparin/fibrin based growth factor delivery system

    Google Scholar 

  102. Blackwood KA, Bock N, Dargaville TR, Ann Woodruff M (2012) Scaffolds for growth factor delivery as applied to bone tissue engineering. Int J Polym Sci. doi:10.1155/2012/174942

    Google Scholar 

  103. García Cruz DM, Sardinha V, Escobar Ivirico JL et al (2013) Gelatin microparticles aggregates as three-dimensional scaffolding system in cartilage engineering. J Mater Sci Mater Med 24:503–513. doi:10.1007/s10856-012-4818-9

    Article  Google Scholar 

  104. Zhang W, Zhu C, Ye D et al (2014) Porous silk scaffolds for delivery of growth factors and stem cells to enhance bone regeneration. PLoS ONE 9:1–9. doi:10.1371/journal.pone.0102371

    Google Scholar 

  105. Almeida HV, Liu Y, Cunniffe GM et al (2014) Controlled release of transforming growth factor-β3 from cartilage-extra-cellular-matrix-derived scaffolds to promote chondrogenesis of human-joint-tissue-derived stem cells. Acta Biomater. doi:10.1016/j.actbio.2014.05.030

    Google Scholar 

  106. Santo VE, Gomes M, Mano J, Reis RL (2012) Controlled release strategies for bone, cartilage and osteochondral engineering—part II: challenges on the evolution from single to multiple bioactive factor delivery. Tissue Eng Part B Rev 19:327–352. doi:10.1089/ten.TEB.2012.0727

    Article  Google Scholar 

  107. Jonitz A, Lochner K, Tischer T et al (2012) TGF-b1 and IGF-1 influence the re-differentiation capacity of human chondrocytes in 3D pellet cultures in relation to different oxygen concentrations. Int J Mol Med 30:666–672. doi:10.3892/ijmm.2012.1042

    Google Scholar 

  108. Loffredo FS, Pancoast JR, Cai L et al (2014) Targeted delivery to cartilage is critical for in vivo efficacy of insulin-like growth factor 1 in a rat model of osteoarthritis. Arthritis Rheumatol (Hoboken, NJ) 66:1247–1255. doi:10.1002/art.38357

    Article  Google Scholar 

  109. Reyes R, Delgado A, Solis R et al (2013) Cartilage repair by local delivery of transforming growth factor-β1 or bone morphogenetic protein-2 from a novel, segmented polyurethane/polylactic-co-glycolic bilayered scaffold. J Biomed Mater Res A. 102:1–11. doi:10.1002/jbma.34769

    Google Scholar 

  110. Lu C-H, Yeh T-S, Fang Y-HD et al (2014) Regenerating cartilages by engineered ASCs: Prolonged TGF-(beta)3/BMP-6 expression improved articular cartilage formation and restored zonal structure. Mol Ther 22:186–195. doi:10.1038/mt.2013.165

    Article  Google Scholar 

  111. Li X, Su G, Wang J et al (2013) Exogenous bFGF promotes articular cartilage repair via up-regulation of multiple growth factors. Osteoarthr Cartil 21:1567–1575. doi:10.1016/j.joca.2013.06.006

    Article  Google Scholar 

  112. Liao J, Hu N, Zhou N et al (2014) Sox9 potentiates BMP2-induced chondrogenic differentiation and inhibits BMP2-induced osteogenic differentiation. PLoS ONE 9:e89025. doi:10.1371/journal.pone.0089025

    Article  Google Scholar 

  113. Zhang Y, Kumagai K, Saito T (2014) Effect of parathyroid hormone on early chondrogenic differentiation from mesenchymal stem cells. J Orthop Surg Res 9:1–7. doi:10.1186/s13018-014-0068-5

    Article  Google Scholar 

  114. Zhang W, Chen J, Zhang S, Ouyang HW (2012) Inhibitory function of parathyroid hormone-related protein on chondrocyte hypertrophy: the implication for articular cartilage repair. Arthritis Res Ther 14:221. doi:10.1186/ar4025

    Article  Google Scholar 

  115. Wu XC, Huang B, Wang J et al (2013) Collagen-targeting parathyroid hormone-related peptide promotes collagen binding and in vitro chondrogenesis in bone marrow-derived MSCs. Int J Mol Med 31:430–436. doi:10.3892/ijmm.2012.1219

    Google Scholar 

  116. Murphy MK, Huey DJ, Hu JC, Athanasiou KA (2014) TGF-β1, GDF-5, and BMP-2 stimulation induces chondrogenesis in expanded human articular chondrocytes and marrow-derived stromal cells. Stem Cells 00:00. doi:10.1002/stem.1890

    Google Scholar 

  117. Mariani E, Pulsatelli L, Facchini A (2014) Signaling pathways in cartilage repair. Int J Mol Sci 15:8667–8698. doi:10.3390/ijms15058667

    Article  Google Scholar 

  118. Gurusinghe S, Strappe P (2014) Gene modification of mesenchymal stem cells and articular chondrocytes to enhance chondrogenesis. Biomed Res Int. doi:10.1155/2014/369528

    Google Scholar 

  119. Croutze R, Jomha N, Uludag H, Adesida A (2013) Matrix forming characteristics of inner and outer human meniscus cells on 3D collagen scaffolds under normal and low oxygen tensions. BMC Musculoskelet Disord 14:353. doi:10.1186/1471-2474-14-353

    Article  Google Scholar 

  120. McNary S, Athanasiou K, Reddi AH (2013) Transforming growth factor beta-induced superficial zone protein accumulation in the surface zone of articular cartilage is dependent on the cytoskeleton. Tissue Eng Part A. doi:10.1089/ten.TEA.2013.0043

    Google Scholar 

  121. Montaseri A, Busch F, Mobasheri A et al (2011) IGF-1 and PDGF-bb suppress IL-1β-induced cartilage degradation through down-regulation of NF-κB signaling: Involvement of Src/PI-3k/AKT pathway. PLoS ONE. doi:10.1371/journal.pone.0028663

    Google Scholar 

  122. Lee JM, Kim B-S, Lee H, Im G-I (2012) In vivo tracking of mesechymal stem cells using fluorescent nanoparticles in an osteochondral repair model. Mol Ther 20:1434–1442. doi:10.1038/mt.2012.60

    Article  Google Scholar 

  123. Montoya F, Martínez F, García-Robles M et al (2013) Clinical and experimental approaches to knee cartilage lesion repair and mesenchymal stem cell chondrocyte differentiation. Biol Res 46:441–451. doi:10.4067/S0716-97602013000400015

    Article  Google Scholar 

  124. Salzmann GM, Sah B, Südkamp NP, Niemeyer P (2013) Clinical outcome following the first-line, single lesion microfracture at the knee joint. Arch Orthop Trauma Surg 133:303–310. doi:10.1007/s00402-012-1660-y

    Article  Google Scholar 

  125. Xu X, Shi D, Shen Y et al (2015) Full-thickness cartilage defects are repaired via a microfracture technique and intra-articular injection of the small molecule compound kartogenin. Arthritis Res Ther. doi:10.1186/s13075-015-0537-1

    Google Scholar 

  126. Goyal D, Keyhani S, Lee EH, Hui JHP (2013) Evidence-based status of microfracture technique: a systematic review of Level I and II studies. Arthrosc J Arthrosc Relat Surg 29:1579–1588. doi:10.1016/j.arthro.2013.05.027

    Article  Google Scholar 

  127. Mobasheri A, Kalamegam G, Musumeci G, Batt ME (2014) Chondrocyte and mesenchymal stem cell-based therapies for cartilage repair in osteoarthritis and related orthopaedic conditions. Maturitas 78:188–198. doi:10.1016/j.maturitas.2014.04.017

    Article  Google Scholar 

  128. Pestka JM, Bode G, Salzmann G et al (2013) Clinical outcomes after cell-seeded autologous chondrocyte implantation of the knee: when can success or failure be predicted? Am J Sports Med 42:208–215. doi:10.1177/0363546513507768

    Article  Google Scholar 

  129. Niemeyer P, Porichis S, Steinwachs M et al (2013) Long-term outcomes after first-generation autologous chondrocyte implantation for cartilage defects of the knee. Am J Sports Med. doi:10.1177/0363546513506593

    Google Scholar 

  130. Minas T, Von Keudell A, Bryant T, Gomoll AH (2014) The John Insall Award: a minimum 10-year outcome study of autologous chondrocyte implantation knee. Clin Orthop Relat Res 472:41–51. doi:10.1007/s11999-013-3146-9

    Article  Google Scholar 

  131. Trinh TQ, Harris JD, Siston RA, Flanigan DC (2013) Improved outcomes with combined autologous chondrocyte implantation and patellofemoral osteotomy versus isolated autologous chondrocyte implantation. Arthrosc J Arthrosc Relat Surg 29:566–574. doi:10.1016/j.arthro.2012.10.008

    Article  Google Scholar 

  132. Filardo G, Kon E, Di MA et al (2012) Second-generation arthroscopic autologous chondrocyte implantation for the treatment of degenerative cartilage lesions. Knee Surg Sport Traumatol Arthrosc 20:1704–1713. doi:10.1007/s00167-011-1732-5

    Article  Google Scholar 

  133. Kreuz PC, Müller S, von Keudell A et al (2013) Influence of sex on the outcome of autologous chondrocyte implantation in chondral defects of the knee. Am J Sports Med 41:1541–1548. doi:10.1177/0363546513489262

    Article  Google Scholar 

  134. Caron MMJ, Emans PJ, Coolsen MME et al (2012) Redifferentiation of dedifferentiated human articular chondrocytes: comparison of 2D and 3D cultures. Osteoarthr Cartil 20:1170–1178. doi:10.1016/j.joca.2012.06.016

    Article  Google Scholar 

  135. Ebert JR, Smith A, Edwards PK et al (2013) Factors predictive of outcome 5 years after matrix-induced autologous chondrocyte implantation in the tibiofemoral joint. Am J Sports Med 41:1245–1254. doi:10.1177/0363546513484696

    Article  Google Scholar 

  136. Ebert JR, Fallon M, Zheng MH et al (2012) A randomized trial comparing accelerated and traditional approaches to postoperative weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation: findings at 5 years. Am J Sports Med 40:1527–1537. doi:10.1177/0363546512445167

    Article  Google Scholar 

  137. Ebert JR, Smith A, Fallon M et al (2014) Correlation between clinical and radiological outcomes after matrix-induced autologous chondrocyte implantation in the femoral condyles. Am J Sports Med 42:1857–1864. doi:10.1177/0363546514534942

    Article  Google Scholar 

  138. Marlovits S, Aldrian S, Wondrasch B et al (2012) Clinical and radiological outcomes 5 years after matrix-induced autologous chondrocyte implantation in patients with symptomatic, traumatic chondral defects. Am J Sports Med 40:2273–2280. doi:10.1177/0363546512457008

    Article  Google Scholar 

  139. Edwards PK, Ackland TR, Ebert JR (2013) Accelerated weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation in the tibiofemoral joint: early clinical and radiological outcomes. Am J Sports Med 41:2314–2324. doi:10.1177/0363546513495637

    Article  Google Scholar 

  140. Saris D, Price A, Widuchowski W et al (2014) Matrix-applied characterized autologous cultured chondrocytes versus microfracture: two-year follow-up of a prospective randomized trial. Am J Sports Med 42:1384–1394. doi:10.1177/0363546514528093

    Article  Google Scholar 

  141. Boeriu CG, Springer J, Kooy FK et al (2013) Production methods for hyaluronan. Int J Carbohydr Chem 2013:1–14. doi:10.1155/2013/624967

    Article  Google Scholar 

  142. Saw K-Y, Anz A, Siew-Yoke Jee C et al (2013) Articular cartilage regeneration with autologous peripheral blood stem cells versus hyaluronic acid: a randomized controlled trial. Arthroscopy 29:684–694. doi:10.1016/j.arthro.2012.12.008

    Article  Google Scholar 

  143. Jang JD, Moon YS, Kim YS et al (2013) Novel repair technique for articular cartilage defect using a fibrin and hyaluronic acid mixture. Tissue Eng Regen Med 10:1–9. doi:10.1007/s13770-013-0361-0

    Article  Google Scholar 

  144. Frith JE, Menzies DJ, Cameron AR et al (2014) Effects of bound versus soluble pentosan polysulphate in PEG/HA-based hydrogels tailored for intervertebral disc regeneration. Biomaterials 35:1150–1162. doi:10.1016/j.biomaterials.2013.10.056

    Article  Google Scholar 

  145. Meng F, He A, Zhang Z et al (2014) Chondrogenic differentiation of ATDC5 and hMSCs could be induced by a novel scaffold-tricalcium phosphate–collagen–hyaluronan without any exogenous growth factors in vitro. J Biomed Mater Res Part A 102:2725–2735. doi:10.1002/jbm.a.34948

    Article  Google Scholar 

  146. Silva-Correia J, Correia SI, Oliveira JM, Reis RL (2013) Tissue engineering strategies applied in the regeneration of the human intervertebral disk. Biotechnol Adv 31:1514–1531. doi:10.1016/j.biotechadv.2013.07.010

    Article  Google Scholar 

  147. Tsaryk R, Silva-Correia J, Oliveira JM et al (2014) Biological performance of cell-encapsulated methacrylated gellan gum-based hydrogels for nucleus pulposus regeneration. J Tissue Eng Regen Med. doi:10.1002/term.1959

    Google Scholar 

  148. Emans PJ, Peterson L (2014) Developing insights in cartilage repair. © Springer, London. doi:10.1007/978-1-4471-5385-6

  149. Jeon JE, Schrobback K, Hutmacher DW, Klein TJ (2012) Dynamic compression improves biosynthesis of human zonal chondrocytes from osteoarthritis patients. Osteoarthr Cartil 20:906–915. doi:10.1016/j.joca.2012.04.019

    Article  Google Scholar 

  150. Tatsumura M, Sakane M, Ochiai N, Mizuno S (2014) Off-loading of cyclic hydrostatic pressure promotes production of extracellular matrix by chondrocytes. Cells Tissues Organs. doi:10.1159/000360156

    Google Scholar 

  151. Sadlik B, Wiewiorski M (2014) Implantation of a collagen matrix for an AMIC repair during dry arthroscopy. Knee Surg Sport Traumatol Arthrosc. doi:10.1007/s00167-014-3062-x

    Google Scholar 

  152. Dhollander A, Moens K, van der Mass J et al (2014) Treatment of patellofemoral cartilage defects in the knee by autologous matrix-induced chondrogenesis (AMIC). Acta Orthop Belg 80:251–259

    Google Scholar 

  153. Piontek T, Ciemniewska-Gorzela K, Szulc A et al (2012) All-arthroscopic AMIC procedure for repair of cartilage defects of the knee. Knee Surg Sport Traumatol Arthrosc 20:922–925. doi:10.1007/s00167-011-1657-z

    Article  Google Scholar 

  154. Athanasiou KA, Eswaramoorthy R, Hadidi P, Hu JC (2013) Self-organization and the self-assembling process in tissue engineering. Annu Rev Biomed Eng 15:115–136. doi:10.1146/annurev-bioeng-071812-152423

    Article  Google Scholar 

  155. Huey DJ, Hu JC, Athanasiou KA (2012) Unlike bone, cartilage regeneration remains elusive. Science (80-) 338:917–921. doi:10.1126/science.1222454

    Article  Google Scholar 

  156. Athanasiou KA, Responte DJ, Brown WE, Hu JC (2015) Harnessing biomechanics to develop cartilage regeneration strategies. J Biomech Eng 137:020901. doi:10.1115/1.4028825

    Article  Google Scholar 

  157. Makris EA, MacBarb RF, Paschos NK et al (2014) Combined use of chondroitinase-ABC, TGF-β1, and collagen crosslinking agent lysyl oxidase to engineer functional neotissues for fibrocartilage repair. Biomaterials 35:6787–6796. doi:10.1016/j.biomaterials.2014.04.083

    Article  Google Scholar 

  158. Makris EA, Hu JC, Athanasiou KA (2013) Hypoxia-induced collagen crosslinking as a mechanism for enhancing mechanical properties of engineered articular cartilage. Osteoarthr Cartil 21:634–641. doi:10.1016/j.joca.2013.01.007

    Article  Google Scholar 

  159. Makris EA, MacBarb RF, Responte DJ et al (2013) A copper sulfate and hydroxylysine treatment regimen for enhancing collagen cross-linking and biomechanical properties in engineered neocartilage. FASEB J 27:2421–2430. doi:10.1096/fj.12-224030

    Article  Google Scholar 

  160. Murphy S, Atala A (2014) 3D bioprinting of tissues and organs. Nat Biotechnol 32(8):494–539

    Article  Google Scholar 

  161. Ozbolat IT, Yu Y (2013) Bioprinting toward organ fabrication: challenges and future trends. IEEE Trans Biomed Eng 60:691–699. doi:10.1109/TBME.2013.2243912

    Article  Google Scholar 

  162. Conese M (2014) Bioprinting: a further step to effective regenerative medicine and tissue engineering. Adv Genet Eng 2:2–5. doi:10.4172/2169-0111.1000e112

    Google Scholar 

  163. Gao G, Yonezawa T, Hubbell K, Dai GCX (2015) Inkjet-bioprinted acrylated peptides and PEG hydrogel with human mesenchymal stem cells promote robust bone and cartilage formation with minimal printhead clogging. Biotechnol J. doi:10.1002/biot.201400635.Submitted

    Google Scholar 

  164. Xu T, Binder KW, Albanna MZ et al (2013) Hybrid printing of mechanically and biologically improved constructs for cartilage tissue engineering applications. Biofabrication 5:015001. doi:10.1088/1758-5082/5/1/015001

    Article  Google Scholar 

  165. Cui X, Boland T, D’Lima D, Lotz M (2012) Thermal inkjet printing in tissue engineering and regenerative medicine. Recent Patents Drug 6:149–155

    Google Scholar 

  166. Cui X, Gao G, Yonezawa T, Dai G (2014) Human cartilage tissue fabrication using three-dimensional inkjet printing technology. J Vis Exp. doi:10.3791/51294

    Google Scholar 

  167. Santhagunam A, Madeira C, Cabral JMS (2012) Genetically engineered stem cell-based strategies for articular cartilage regeneration. Biotechnol Appl Biochem 59:121–131. doi:10.1002/bab.1016

    Article  Google Scholar 

  168. Lorda-Diez CI, Montero JA, Garcia-Porrero JA, Hurle JM (2014) Divergent differentiation of skeletal progenitors into cartilage and tendon: lessons from the embryonic limb. ACS Chem Biol 9:72–79. doi:10.1021/cb400713

    Article  Google Scholar 

  169. Lu C-H, Lin K-J, Chiu H-Y et al (2012) Improved chondrogenesis and engineered cartilage formation from TGF-β3-expressing adipose-derived stem cells cultured in the rotating-shaft bioreactor. Tissue Eng Part A 18:2114–2124. doi:10.1089/ten.tea.2012.0010

    Article  Google Scholar 

  170. Madry H, Kaul G, Zurakowski D et al (2013) Cartilage constructs engineered from chondrocytes overexpressing IGF-I improve the repair of osteochondral defects in a rabbit model. Eur Cells Mater 25:229–247

    Google Scholar 

  171. Hu Y-C (2014) Gene Therapy for Cartilage and Bone Tissue Engineering. Gene Ther Cartil Bone Tissue Eng 2:1–15. doi:10.1007/978-3-642-53923-7

    Article  Google Scholar 

  172. Madeira C, Santhagunam A, Salgueiro JB, Cabral JMS (2015) Advanced cell therapies for articular cartilage regeneration. Trends Biotechnol 33:35–42. doi:10.1016/j.tibtech.2014.11.003

    Article  Google Scholar 

  173. Brunger JM, Huynh NPT, Guenther CM et al (2014) Scaffold-mediated lentiviral transduction for functional tissue engineering of cartilage. Proc Natl Acad Sci USA 111:E798–E806. doi:10.1073/pnas.1321744111

    Article  Google Scholar 

  174. Cucchiarini M, Madry H (2014) Overexpression of human IGF-I via direct rAAV-mediated gene transfer improves the early repair of articular cartilage defects in vivo. Gene Ther 21:1–9. doi:10.1038/gt.2014.58

    Article  Google Scholar 

  175. Cucchiarini M, Orth P, Madry H (2013) Direct rAAV SOX9 administration for durable articular cartilage repair with delayed terminal differentiation and hypertrophy in vivo. J Mol Med 91:625–636. doi:10.1007/s00109-012-0978-9

    Article  Google Scholar 

  176. Goodrich LR, Phillips JN, McIlwraith CW et al (2013) Optimization of scAAVIL-1ra in vitro and in vivo to deliver high levels of therapeutic protein for treatment of osteoarthritis. Mol Ther Nucleic Acids 2:e70. doi:10.1038/mtna.2012.61

    Article  Google Scholar 

  177. Ha C-W, Noh MJ, Choi KB, Lee KH (2012) Initial phase I safety of retrovirally transduced human chondrocytes expressing transforming growth factor-beta-1 in degenerative arthritis patients. Cytotherapy 14:247–256. doi:10.3109/14653249.2011.629645

    Article  Google Scholar 

  178. Li X, Ellman MB, Kroin JS et al (2012) Species-specific biological effects of FGF-2 in articular cartilage: implication for distinct roles within the FGF receptor family. J Cell Biochem 113:2532–2542. doi:10.1002/jcb.24129

    Article  Google Scholar 

  179. Watson R, Broome T, Levings P et al (2013) scAAV-mediated gene transfer of Interleukin 1-receptor antagonist to synovium and articular cartilage in large mammalian joints. Gene Ther 20:670–677. doi:10.1038/gt.2012.81.scAAV-Mediated

    Article  Google Scholar 

  180. Gascón AR, del Pozo-Rodríguez A, Solinís MÁ (2014) Non-viral delivery systems in gene therapy. Gene Ther Tools Potential Appl. doi:10.5772/52704

    Google Scholar 

  181. He CX, Zhang TY, Miao PH et al (2012) TGF-β1 gene-engineered mesenchymal stem cells induce rat cartilage regeneration using nonviral gene vector. Biotechnol Appl Biochem 59:163–169. doi:10.1002/bab.1001

    Article  Google Scholar 

  182. Oliveira PH, Mairhofer J (2013) Marker-free plasmids for biotechnological applications—implications and perspectives. Trends Biotechnol 31:539–547. doi:10.1016/j.tibtech.2013.06.001

    Article  Google Scholar 

  183. Li P, Wei X, Guan Y et al (2014) MicroRNA-1 regulates chondrocyte phenotype by repressing histone deacetylase 4 during growth plate development. FASEB J 28:3930–3941. doi:10.1096/fj.13-249318

    Article  Google Scholar 

  184. Qi B, Yu A, Zhu S et al (2013) Chitosan/poly(vinyl alcohol) hydrogel combined with Ad-hTGF-β1 transfected mesenchymal stem cells to repair rabbit articular cartilage defects. Exp Biol Med (Maywood) 238:23–30. doi:10.1258/ebm.2012.012223

    Article  Google Scholar 

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  1. 3B’s Research Group—Biomaterials, Biodegradables and Biomimetics, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of Minho, AvePark, S. Claudio de Barco, Guimarães, Portugal

    Alain da Silva Morais, Joaquim Miguel Oliveira & Rui Luís Reis

  2. ICVS/3B’s—PT Government Associate Laboratory, Braga, Guimarães, Portugal

    Alain da Silva Morais, Joaquim Miguel Oliveira & Rui Luís Reis

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da Silva Morais, A., Oliveira, J.M., Reis, R.L. (2017). Cartilage Tissue Engineering and Regenerative Strategies. In: Oliveira, J., Reis, R. (eds) Regenerative Strategies for the Treatment of Knee Joint Disabilities. Studies in Mechanobiology, Tissue Engineering and Biomaterials, vol 21. Springer, Cham. https://doi.org/10.1007/978-3-319-44785-8_5

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