Skip to main content
SpringerLink
Log in

Challenges for Cartilage Regeneration

  • Chapter
  • First Online:
Book cover Biomaterials for Implants and Scaffolds

Part of the book series: Springer Series in Biomaterials Science and Engineering ((SSBSE,volume 8))

Abstract

Articular cartilage is a resilient connective tissue, which covers the surface of bones to facilitate their movements against each other. Due to unique mechanical properties, cartilage has a prominent role in locomotion and mobility of the human body. This tissue however has limited capability of regeneration and repair due to its low metabolism and avascular structure. Trauma, degenerative conditions and inflammatory arthritis lead to lifetime disability states and pain. The scope of this chapter is to first provide an overview of mechanical, biological and micro-architectural properties of articular cartilage and the effect of aging on these characteristics. Then the cartilage treatment techniques that have been proposed for different types of cartilage defects are discussed. Cell-based therapies, such as autologous chondrocyte implantation (ACI) technique, have been developed to achieve reproducible results regardless of patients’ age, gender and physical conditions. The second generation of ACI is a tissue engineering-based technique, which includes the use of appropriate cell type, bioactive molecules such as growth factors and proper scaffold to regenerate cartilage. The favourable types of cells, biological compounds and properties of biomaterials for cartilage regeneration have also been discussed in this chapter. Finally, the biomaterial products that have been examined in clinical trial for cartilage repair are outlined, and their properties and clinical results are discussed.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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

Notes

  1. 1.

    Human (and other) somatic cells without telomerase gradually lose telomeric sequences as a result of incomplete replication.

  2. 2.

    Hydrogel is formed through condensation process upon decrease of solubility of polymer in aqueous solution.

  3. 3.

    HEPES is a buffer solution, widely used in vitro cell culturing to maintain neutral pH in media.

  4. 4.

    Pluronic® is triblock copolymer of PEO–PPO–PEO.

References

  1. Simon TM, Jackson DW (2006) Articular cartilage: injury pathways and treatment options. Sports Med Arthrosc 14:146–154

    Article  Google Scholar 

  2. Mankin HJ (1982) The response of articular cartilage to mechanical injury. J Bone Joint Surg Am 64:460–466

    Article  Google Scholar 

  3. LaPorta TF, Richter A, Sgaglione NA, Grande DA (2012) Clinical relevance of scaffolds for cartilage engineering. Orthop Clin N Am 43:245–254

    Article  Google Scholar 

  4. Brittberg M (2010) Cell carriers as the next generation of cell therapy for cartilage repair: a review of the matrix-induced autologous chondrocyte implantation procedure. Am J Sports Med 38:1259–1271

    Article  Google Scholar 

  5. Poole CA (1993) The structure and function of articular cartilage matrixes. Inflamm Dis Ther 12:1–35

    Google Scholar 

  6. Wu W, Billinghurst RC, Pidoux I, Antoniou J, Zukor D, Tanzer M et al (2002) Sites of collagenase cleavage and denaturation of type II collagen in aging and osteoarthritic articular cartilage and their relationship to the distribution of matrix metalloproteinase 1 and matrix metalloproteinase 13. Arthritis Rheum 46:2087–2094

    Article  Google Scholar 

  7. McCarty WJ, Nguyen QT, Hui AY, Chen AC, Sah RL (2011) Comprehensive biomaterials. Elsevier, London

    Google Scholar 

  8. Deshmukh K, Nimni ME (1973) Isolation and characterization of cyanogen bromide peptides from the collagen of bovine articular cartilage. Biochem J 133:615–622

    Article  Google Scholar 

  9. Eyre DR, Wu J-J (1995) Collagen structure and cartilage matrix integrity. J Rheumatol Suppl 43:82–85

    Google Scholar 

  10. Roughley PJ, Lee ER (1994) Cartilage proteoglycans: structure and potential functions. Microsc Res Tech 28:385–397

    Article  Google Scholar 

  11. Watanabe H, Yamada Y, Kimata K (1998) Roles of aggrecan, a large chondroitin sulfate proteoglycan, in cartilage structure and function. J Biochem 124:687–693

    Article  Google Scholar 

  12. Maroudas A, Muir H, Wingham J (1969) Correlation of fixed negative charge with glycosaminoglycan content of human articular cartilage. Biochim Biophys Acta Gen Subj 177:492–500

    Article  Google Scholar 

  13. Ateshian GA, Lai WM, Zhu WB, Mow VC (1994) An asymptotic solution for the contact of two biphasic cartilage layers. J Biomech 27:1347–1360

    Article  Google Scholar 

  14. Broom ND (1984) Further insights into the structural principles governing the function of articular cartilage. J Anat 139(Pt 2):275–294

    Google Scholar 

  15. Boskey AL (1981) Current concepts of the physiology and biochemistry of calcification. Clin Orthop Relat Res 157:225–257

    Google Scholar 

  16. Poole AR, Matsui Y, Hinek A, Lee ER (1989) Cartilage macromolecules and the calcification of cartilage matrix. Anat Rec 224:167–179

    Article  Google Scholar 

  17. Hall FM, Wyshak G (1980) Thickness of articular cartilage in the normal knee. J Bone Joint Surg Am 62:408–413

    Article  Google Scholar 

  18. MacConaill MA (1951) The movements of bones and joints; the mechanical structure of articulating cartilage. J Bone Joint Surg (Br) 33B:251–257

    Google Scholar 

  19. Stockwell RA (1971) The interrelationship of cell density and cartilage thickness in mammalian articular cartilage. J Anat 109:411–421

    Google Scholar 

  20. Radin EL, Rose RM (1986) Role of subchondral bone in the initiation and progression of cartilage damage. Clin Orthop Relat Res 213:34–40

    Google Scholar 

  21. Hunziker EB, Herrmann W, Schenk RK (1983) Ruthenium hexammine trichloride (RHT)-mediated interaction between plasmalemmal components and pericellular matrix proteoglycans is responsible for the preservation of chondrocytic plasma membranes in situ during cartilage fixation. J Histochem Cytochem 31:717–727

    Article  Google Scholar 

  22. Kumar P, Oka M, Toguchida J, Kobayashi M, Uchida E, Nakamura T et al (2001) Role of uppermost superficial surface layer of articular cartilage in the lubrication mechanism of joints. J Anat 199:241–250

    Article  Google Scholar 

  23. Wu JP, Kirk TB, Zheng MH (2008) Study of the collagen structure in the superficial zone and physiological state of articular cartilage using a 3D confocal imaging technique. J Orthop Surg Res 3:29

    Article  Google Scholar 

  24. Mathew G, Hanson BP (2009) Global burden of trauma: need for effective fracture therapies. Indian J Orthop 43:111–116

    Article  Google Scholar 

  25. Temple MM, Bae WC, Chen MQ, Lotz M, Amiel D, Coutts RD et al (2007) Age- and site-associated biomechanical weakening of human articular cartilage of the femoral condyle. Osteoarthr Cartil 15:1042–1052

    Article  Google Scholar 

  26. Mansour JM, Mow VC (1976) The permeability of articular cartilage under compressive strain and at high pressures. J Bone Joint Surg Am 58:509–516

    Article  Google Scholar 

  27. Freeman MAR (1979) Adult articular cartilage. Pitman Medical, Tunbridge Wells

    Google Scholar 

  28. Chen AC, Bae WC, Schinagl RM, Sah RL (2001) Depth- and strain-dependent mechanical and electromechanical properties of full-thickness bovine articular cartilage in confined compression. J Biomech 34:1–12

    Article  Google Scholar 

  29. Williamson AK, Chen AC, Masuda K, Thonar EJMA, Sah RL (2003) Tensile mechanical properties of bovine articular cartilage: variations with growth and relationships to collagen network components. J Orthop Res 21:872–880

    Article  Google Scholar 

  30. Johannessen W, Elliott DM (2005) Effects of degeneration on the biphasic material properties of human nucleus pulposus in confined compression. Spine (Phila Pa 1976) 30:E724–E729

    Article  Google Scholar 

  31. Schinagl RM, Gurskis D, Chen AC, Sah RL (1997) Depth-dependent confined compression modulus of full-thickness bovine articular cartilage. J Orthop Res 15:499–506

    Article  Google Scholar 

  32. Athanasiou KA, Agarwal A, Dzida FJ (1994) Comparative study of the intrinsic mechanical properties of the human acetabular and femoral head cartilage. J Orthop Res 12:340–349

    Article  Google Scholar 

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

    Article  Google Scholar 

  34. Changoor A, Fereydoonzad L, Yaroshinsky A, Buschmann MD (2010) Effects of refrigeration and freezing on the electromechanical and biomechanical properties of articular cartilage. J Biomech Eng 132:064502

    Article  Google Scholar 

  35. Bray JC, Merrill EW (1973) Poly(vinyl alcohol) hydrogels for synthetic articular cartilage material. J Biomed Mater Res 7:431–443

    Article  Google Scholar 

  36. Buckley MR, Gleghorn JP, Bonassar LJ, Cohen I (2008) Mapping the depth dependence of shear properties in articular cartilage. J Biomech 41:2430–2437

    Article  Google Scholar 

  37. Setton LA, Mow VC, Howell DS (1995) Mechanical behavior of articular cartilage in shear is altered by transection of the anterior cruciate ligament. J Orthop Res 13:473–482

    Article  Google Scholar 

  38. Linn FC (1967) Lubrication of animal joints. I. The arthrotripsometer. J Bone Joint Surg Am 49:1079–1098

    Article  Google Scholar 

  39. Athanasiou KA, Rosenwasser MP, Buckwalter JA, Malinin TI, Mow VC (1991) Interspecies comparisons of in situ intrinsic mechanical properties of distal femoral cartilage. J Orthop Res 9:330–340

    Article  Google Scholar 

  40. Maroudas A, Bullough P (1968) Permeability of articular cartilage. Nature 219:1260–1261

    Article  Google Scholar 

  41. Basalo IM, Mauck RL, Kelly T-AN, Nicoll SB, Chen FH, Hung CT et al (2004) Cartilage interstitial fluid load support in unconfined compression following enzymatic digestion. J Biomech Eng 126:779–786

    Article  Google Scholar 

  42. Armstrong CG, Bahrani AS, Gardner DL (1979) In vitro measurement of articular cartilage deformations in the intact human hip joint under load. J Bone Joint Surg Am 61:744–755

    Article  Google Scholar 

  43. Akizuki S, Mow VC, Muller F, Pita JC, Howell DS, Manicourt DH (1986) Tensile properties of human knee joint cartilage: I. Influence of ionic conditions, weight bearing, and fibrillation on the tensile modulus. J Orthop Res 4:379–392

    Article  Google Scholar 

  44. Freeman MA (1969) Tensile properties of articular cartilage. Nature 220:1127–1128

    Google Scholar 

  45. Roth V, Mow VC (1980) The intrinsic tensile behavior of the matrix of bovine articular cartilage and its variation with age. J Bone Joint Surg Am 62:1102–1117

    Article  Google Scholar 

  46. Kempson GE, Muir H, Pollard C, Tuke M (1973) Tensile properties of the cartilage of human femoral condyles related to the content of collagen and glycosaminoglycans. Biochim Biophys Acta Gen Subj 297:456–472

    Article  Google Scholar 

  47. Schmidt MB, Mow VC, Chun LE, Eyre DR (1990) Effects of proteoglycan extraction on the tensile behavior of articular cartilage. J Orthop Res 8:353–363

    Article  Google Scholar 

  48. Williamson AK, Chen AC, Sah RL (2001) Compressive properties and function—composition relationships of developing bovine articular cartilage. J Orthop Res 19:1113–1121

    Article  Google Scholar 

  49. Hayes WC, Mockros LF (1971) Viscoelastic properties of human articular cartilage. J Appl Physiol 31:562–568

    Google Scholar 

  50. Belyi VA, Kupchinov BI, Ermakov SF, Rodnenkov VG, Bobrysheva SN (1988) Lubricants to recover tribological properties of human joints. Int SAMPE Symp Exhib 33:645–651

    Google Scholar 

  51. Dowson D, Jin ZM (1986) Micro-elastohydrodynamic lubrication of synovial joints. Eng Med 15:63–65

    Article  Google Scholar 

  52. Krishnan R, Kopacz M, Ateshian GA (2004) Experimental verification of the role of interstitial fluid pressurization in cartilage lubrication. J Orthop Res 22:565–570

    Article  Google Scholar 

  53. Kupchinov BI (1989) Tribological aspects of the functioning of joints. Trenie Iznos 10:1013–1018

    Google Scholar 

  54. Armstrong CG, Gardner DL (1977) Thickness and distribution of human femoral head articular cartilage. Changes with age. Ann Rheum Dis 36:407–412

    Article  Google Scholar 

  55. Meachim G (1971) Effect of age on the thickness of adult articular cartilage at the shoulder joint. Ann Rheum Dis 30:43–46

    Article  Google Scholar 

  56. Vignon E, Arlot M, Vignon G (1977) The cellularity of fibrillated articular cartilage. A comparative study of age-related and osteoarthrotic cartilage lesions from the human femoral head. Pathol Biol 25:29–32

    Google Scholar 

  57. Adams CS, Horton WE Jr (1998) Chondrocyte apoptosis increases with age in the articular cartilage of adult animals. Anat Rec 250:418–425

    Article  Google Scholar 

  58. Barbero A, Grogan S, Schafer D, Heberer M, Mainil-Varlet P, Martin I (2004) Age related changes in human articular chondrocyte yield, proliferation and post-expansion chondrogenic capacity. Osteoarthr Cartil 12:476–484

    Article  Google Scholar 

  59. Eyre DR, Dickson IR, Van NK (1988) Collagen cross-linking in human bone and articular cartilage. Age-related changes in the content of mature hydroxypyridinium residues. Biochem J 252:495–500

    Article  Google Scholar 

  60. Axelsson I, Bjelle A (1979) Proteoglycan structure of bovine articular cartilage. Variation with age and in osteoarthrosis. Scand J Rheumatol 8:217–221

    Article  Google Scholar 

  61. Bank RA, Bayliss MT, Lafeber FPJG, Maroudas A, Tekoppele JM (1998) Osteochondral resurfacing of the knee joint with allograft. Clinical analysis of 33 cases. Biochem J 330:345–351

    Article  Google Scholar 

  62. Ding M (2000) Age variations in the properties of human tibial trabecular bone and cartilage. Acta Orthop Scand Suppl 292:1–45

    Article  Google Scholar 

  63. Hyttinen MM, Arokoski JP, Parkkinen JJ, Lammi MJ, Lapvetelainen T, Mauranen K et al (2001) Age matters: collagen birefringence of superficial articular cartilage is increased in young guinea-pigs but decreased in older animals after identical physiological type of joint loading. Osteoarthr Cartil 9:694–701

    Article  Google Scholar 

  64. Turner AS, Athanasiou KA, Zhu CF, Alvis MR, Bryant HU (1997) Biochemical effects of estrogen on articular cartilage in ovariectomized sheep. Osteoarthr Cartil 5:63–69

    Article  Google Scholar 

  65. Murray RC, DeBowes RM, Gaughan EM, Zhu CF, Athanasiou KA (1998) The effects of intra-articular methylprednisolone and exercise on the mechanical properties of articular cartilage in the horse. Osteoarthr Cartil 6:106–114

    Article  Google Scholar 

  66. Athanasiou KA, Fleischli JG, Bosma J, Laughlin TJ, Zhu CF, Agrawal CM et al (1999) Effects of diabetes mellitus on the biomechanical properties of human ankle cartilage. Clin Orthop Relat Res 182–9

    Google Scholar 

  67. Wluka AE, Wang Y, Davis SR, Cicuttini FM (2005) Tibial plateau size is related to grade of joint space narrowing and osteophytes in healthy women and in women with osteoarthritis. Ann Rheum Dis 64:1033–1037

    Article  Google Scholar 

  68. Aspden RM, Jeffrey JE, Burgin LV (2002) Impact loading of articular cartilage. Osteoarthr Cartil 10:588–589; author reply 90.

    Google Scholar 

  69. Lohmander LS, Ostenberg A, Englund M, Roos H (2004) High prevalence of knee osteoarthritis, pain, and functional limitations in female soccer players twelve years after anterior cruciate ligament injury. Arthritis Rheum 50:3145–3152

    Article  Google Scholar 

  70. Roos H, Adalberth T, Dahlberg L, Lohmander LS (1995) Osteoarthritis of the knee after injury to the anterior cruciate ligament or meniscus: the influence of time and age. Osteoarthr Cartil 3:261–267

    Article  Google Scholar 

  71. A picture of osteoarthritis in Australia. Australian Institute of Health and Welfare; 2007 series no. 5, Cat. no. PHE 93, Canberra: AIHW

    Google Scholar 

  72. Painful realities: The economic impact of arthritis in Australia. Canberra: Arthritis Australia 2012

    Google Scholar 

  73. Ahmed TAE, Hincke MT (2010) Strategies for articular cartilage lesion repair and functional restoration. Tissue Eng Part B 16:305–329

    Article  Google Scholar 

  74. Goldberg VM, Caplan AI, Barry FP, Fink DJ, Marshak DR, Burns JS (2002) Osteoarthritis cartilage regeneration. Osiris Therapeutics, Inc., Columbia

    Google Scholar 

  75. McCormick F, Yanke A, Provencher MT, Cole BJ (2008) Minced articular cartilage – basic science, surgical technique, and clinical application. Sports Med Arthrosc 16:217–220

    Article  Google Scholar 

  76. Furukawa T, Eyre DR, Koide S, Glimcher MJ (1980) Biochemical studies on repair cartilage resurfacing experimental defects in the rabbit knee. J Bone Joint Surg Am 62(A):79–89

    Article  Google Scholar 

  77. Shapiro F, Koide S, Glimcher MJ (1993) Cell origin and differentiation in the repair of full-thickness defects of articular cartilage. J Bone Joint Surg Am 75:532–553

    Article  Google Scholar 

  78. Hjertquist SO, Lemperg R (1971) Histological, autoradiographic, and microchemical studies of spontaneously healing osteochondral articular defects in adult rabbits. Calcif Tissue Res 8:54–72

    Article  Google Scholar 

  79. Temenoff JS, Mikos AG (2000) Review: tissue engineering for regeneration of articular cartilage. Biomaterials 21:431–440

    Article  Google Scholar 

  80. Adachi N, Ishikawa M, Sera S, Ochi M (2007) Articular cartilage regeneration (Knee joint). Bone 21:473–476

    Google Scholar 

  81. Ghadially JA, Ghadially R, Ghadially FN (1977) Long-term results of deep defects in articular cartilage. A scanning electron microscope study. Virchows Arch B Cell Pathol 25:125–136

    Google Scholar 

  82. Squires GR, Okouneff S, Ionescu M, Poole AR (2003) The pathobiology of focal lesion development in aging human articular cartilage and molecular matrix changes characteristic of osteoarthritis. Arthritis Rheum 48:1261–1270

    Article  Google Scholar 

  83. Chang RW, Falconer J, Stulberg SD, Arnold WJ, Manheim LM, Dyer AR (1993) A randomized, controlled trial of arthroscopic surgery versus closed- needle joint lavage for patients with osteoarthritis of the knee. Arthritis Rheum 36:289–296

    Article  Google Scholar 

  84. Ike RW, Arnold WJ (1992) Arthroscopic lavage of osteoarthritic knees. J Bone Joint Surg – B 74:788–789

    Google Scholar 

  85. Hunziker EB, Kapfinger E (1998) Removal of proteoglycans from the surface of defects in articular cartilage transiently enhances coverage by repair cells. J Bone Joint Surg – B 80:144–150

    Article  Google Scholar 

  86. Felson DT (2010) Arthroscopy as a treatment for knee osteoarthritis. Best Pract Res Clin Rheumatol 24:47–50

    Article  Google Scholar 

  87. Anderson MA, Payne JT, Kreeger JM, Wagner-Mann CC, Schmidt DA, Mann FA (1993) Effects of intra-articular chlorhexidine diacetate lavage on the stifle in healthy dogs. Am J Vet Res 54:1784–1789

    Google Scholar 

  88. Hunziker EB (2002) Articular cartilage repair: Basic science and clinical progress. A review of the current status and prospects. Osteoarthr Cartil 10:432–463

    Article  Google Scholar 

  89. Tew SR, Kwan APL, Hann A, Thomson BM, Archer CW (2000) The reactions of articular cartilage to experimental wounding: Role of apoptosis. Arthritis Rheum 43:215–225

    Article  Google Scholar 

  90. Mitchell N, Shepard N (1987) Effect of Patellar Shaving in the Rabbit. J Orthop Res 5:388–392

    Article  Google Scholar 

  91. Hunziker EB, Quinn TM (2003) Surgical removal of articular cartilage leads to loss of chondrocytes from cartilage bordering the wound edge. J Bone Joint Surg – A 85:85–92

    Article  Google Scholar 

  92. McLaren AC, Blokker CP, Fowler PJ, Roth JN, Rock MG (1991) Arthroscopic debridement of the knee for osteoarthrosis. Can J Surg 34:595–598

    Google Scholar 

  93. Messner K, Fahlgren A, Ross I, Andersson B (2000) Simultaneous changes in bone mineral density and articular cartilage in a rabbit meniscectomy model of knee osteoarthrosis. Osteoarthr Cartil 8:197–206

    Article  Google Scholar 

  94. Messner K, Fahlgren A, Persliden J, Andersson BM (2001) Radiographic joint space narrowing and histologic changes in a rabbit meniscectomy model of early knee osteoarthrosis. Am J Sports Med 29:151–160

    Google Scholar 

  95. Müller B, Kohn D (1999) Indication for and performance of articular cartilage drilling using the Pridie method. Orthopade 28:4–10

    Google Scholar 

  96. Insall JN (1967) Intra-articular surgery for degenerative arthritis of the knee. A report of the work of the late K. H. Pridie. J Bone Joint Surg (Br) 49:211–228

    Google Scholar 

  97. Insall J (1974) The Pridie debridement operation for osteoarthritis of the knee. Clin Orthop Relat Res 101:61–67

    Google Scholar 

  98. Goldman RT, Scuderi GR, Kelly MA (1997) Arthroscopic treatment of the degenerative knee in older athletes. Clin Sports Med 16:51–68

    Article  Google Scholar 

  99. Beiser IH, Kanat IO (1990) Subchondral bone drilling: a treatment for cartilage defect. J Foot Surg 29:595–601

    Google Scholar 

  100. Hice G, Freedman D, Lemont H, Khoury S (1990) Scanning and light microscopic study of irrigated and nonirrigated joints following burr surgery performed through a small incision. J Foot Surg 29:337–344

    Google Scholar 

  101. Schmidt H, Schulze KJ, Cyffka R (1988) Results of treatment of cartilage damage by Pridie drilling of the knee joint. Ergebnisse der Behandlung von Knorpelschäden durch PRIDIE-Bohrung am Kniegelen 35:117–122

    Google Scholar 

  102. Breinan HA, Martin SD, Hsu HP, Spector M (2000) Healing of canine articular cartilage defects treated with microfracture, a type-II collagen matrix, or cultured autologous chondrocytes. J Orthop Res 18:781–789

    Article  Google Scholar 

  103. Sledge SL (2001) Microfracture techniques in the treatment of osteochondral injuries. Clin Sports Med 20:365–378

    Article  Google Scholar 

  104. Pittenger MF, Mosca JD, McIntosh KR (2000) Human mesenchymal stem cells: progenitor cells for cartilage, bone, fat and stroma. 3–11.

    Google Scholar 

  105. Paccola CAJ, Xavier CAM, Goncalves RP (1979) Fresh immature articular cartilage allografts. A study on the integration of chondral and osteochondral grafts both in normal and in papain-treated knee joints of rabbits. Arch Orthop Trauma Surg 93:253–259

    Article  Google Scholar 

  106. Lee TQ, Shrader TA, Wang YP, Glaser FE, Kim WC, McMahon PJ (1999) The use of entire fresh patellar allograft for articular cartilage replacement in rabbits: a long-term interdisciplinary study. J Musculoskelet Res 3:305–316

    Article  Google Scholar 

  107. Stevenson S (1987) The immune response to osteochondral allografts in dogs. J Bone Joint Surg Am 69:573–582

    Article  Google Scholar 

  108. Hickey MJ, Ohta I, Shigetomi M, Hurley JV, Kuwata N, O’Brien BM (1994) Vascularized heterotopic osteochondral allografts in a rat model following long-term immunosuppression. J Reconstr Microsurg 10:255–260

    Article  Google Scholar 

  109. Bakay A, Csonge L, Papp G, Fekete L (1998) Osteochondral resurfacing of the knee joint with allograft. Clinical analysis of 33 cases. Int Orthop 22:277–281

    Article  Google Scholar 

  110. Bell RS, Davis A, Allan DG, Langer F, Czitrom AA, Gross AE (1994) Fresh osteochondral allografts for advanced giant cell tumors at the knee. J Arthroplasty 9:603–609

    Article  Google Scholar 

  111. Marco F, Lopez-Oliva F, Fernandez F-AJM, de Pedro JA, Perez AJ, Leon C et al (1993) Osteochondral allografts for osteochondritis dissecans and osteonecrosis of the femoral condyles. Int Orthop 17:104–108

    Article  Google Scholar 

  112. McDermott AG, Langer F, Pritzker KP, Gross AE (1985) Fresh small-fragment osteochondral allografts. Long-term follow-up study on first 100 cases. Clin Orthop Relat Res 197:96–102

    Google Scholar 

  113. Mahomed MN, Beaver RJ, Gross AE (1992) The long-term success of fresh, small fragment osteochondral allografts used for intraarticular post-traumatic defects in the knee joint. Orthopedics 15:1191–1199

    Google Scholar 

  114. Kreuz PC, Steinwachs MR, Erggelet C, Krause SJ, Konrad G, Uhl M et al (2006) Results after microfracture of full-thickness chondral defects in different compartments in the knee. Osteoarthr Cartil 14:1119–1125

    Article  Google Scholar 

  115. Jamali AA, Emmerson BC, Chung C, Convery FR, Bugbee WD (2005) Fresh osteochondral allografts: results in the patellofemoral joint. Clin Orthop Relat Res 437:176–185

    Article  Google Scholar 

  116. Torga SR, Teitge RA (2006) Fresh osteochondral allografts for patellofemoral arthritis: long-term follow up. Clin Orthop Relat Res 444:193–200

    Google Scholar 

  117. Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L (1994) Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med 331:889–895

    Article  Google Scholar 

  118. Trattnig S, Millington SA, Marlovits S (2007) MR imaging of osteochondral grafts and autologous chondrocyte implantation. Eur Radiol 17:103–118

    Article  Google Scholar 

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

    Article  Google Scholar 

  120. Kuroda T, Matsumoto T, Mifune Y, Fukui T, Kubo S, Matsushita T et al (2011) Therapeutic strategy of third-generation autologous chondrocyte implantation for osteoarthritis. Ups J Med Sci 116:107–114

    Article  Google Scholar 

  121. Tandogan NR, Karaeminogullari O, Ozyurek A, Ersozlu S (2004) Periarticular fractures of the knee in child and adolescent athletes. Acta Orthop Traumatol Turc 38(Suppl 1):93–100

    Google Scholar 

  122. Parkkari J, Pasanen K, Mattila VM, Kannus P, Rimpela A (2008) The risk for a cruciate ligament injury of the knee in adolescents and young adults: a population-based cohort study of 46 500 people with a 9 year follow-up. Br J Sports Med 42:422–426

    Article  Google Scholar 

  123. Hickey GJ, Fricker PA, McDonald WA (1997) Injuries of young elite female basketball players over a six-year period. Clin J Sport Med 7:252–256

    Article  Google Scholar 

  124. Adirim TA, Cheng TL (2003) Overview of injuries in the young athlete. Sports Med 33:75–81

    Article  Google Scholar 

  125. Tuli R, Li W-J, Tuan RS (2003) Current state of cartilage tissue engineering. Arthritis Res Ther 5:235–238

    Article  Google Scholar 

  126. Iwasa J, Engebretsen L, Shima Y, Ochi M (2009) Clinical application of scaffolds for cartilage tissue engineering. Knee Surg Sports Traumatol Arthrosc 17:561–577

    Article  Google Scholar 

  127. Le DC, Guery J, Laulan J (2004) Results of a five-year series of 44 trapeziectomies associated with ligamentoplasty and interposition arthroplasty. Chir Main 23:149–152

    Article  Google Scholar 

  128. Bruns J, Kersten P, Lierse W, Silbermann M (1993) Autologous transplantation of rib perichondrium in treatment of deep cartilage defects of the knee joint of sheep. Morphologic comparison of two resorbable fixation methods. Unfallchirurg 96:462–467

    Google Scholar 

  129. Getgood A, Brooks R, Fortier L, Rushton N (2009) Articular cartilage tissue engineering: today’s research, tomorrow’s practice? J Bone Joint Surg (Br) 91:565–576

    Article  Google Scholar 

  130. Langer RS, Vacanti JP (1993) Tissue engineering. Science 260:920–926

    Article  Google Scholar 

  131. Park I-K, Cho C-S (2010) Stem cell-assisted approaches for cartilage tissue engineering. Int J Stem Cells 3:96–102

    Article  Google Scholar 

  132. Kim IL, Mauck RL, Burdick JA (2011) Hydrogel design for cartilage tissue engineering: a case study with hyaluronic acid. Biomaterials 32:8771–8782

    Article  Google Scholar 

  133. Hwang NS, Elisseeff J (2009) Application of stem cells for articular cartilage regeneration. J Knee Surg 22:60–71

    Article  Google Scholar 

  134. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147

    Article  Google Scholar 

  135. Noël D, Djouad FCJ (2002) Regenerative medicine through mesenchymal stem cells for bone and cartilage repair. Curr Opin Investig Drugs 3:1000–1004

    Google Scholar 

  136. Barry FPMJ (2004) Mesenchymal stem cells: clinical applications and biological characterization. Int J Biochem Cell Biol 36:568–584

    Article  Google Scholar 

  137. Trubiani ODPR, Traini T, Pizzicannella J, Scarano A, Piattelli A, Caputi S (2005) Morphological and cytofluorimetric analysis of adult mesenchymal stem cells expanded ex vivo from periodontal ligament. Int J Immunopathol Pharmacol 18:213–221

    Google Scholar 

  138. Trubiani OOG, Caputi S, Piatelli A (2006) Adult mesenchymal stem cells in dental research: a new approach for tissue engineering. Int J Immunopathol Pharmacol 19:451–460

    Google Scholar 

  139. Caplan AI (2007) Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J Cell Physiol 213:341–347

    Article  Google Scholar 

  140. Nejadnik H, Hui JH, Feng Choong EP, Tai BC, Lee EH (2010) Autologous bone marrow-derived mesenchymal stem cells versus autologous chondrocyte implantation: an observational cohort study. Am J Sports Med 6:1110–1116

    Article  Google Scholar 

  141. Fan HHY, Zhang C, Li X, Lv R, Qin L, Zhu R (2006) Cartilage regeneration using mesenchymal stem cells and a PLGA-gelatin/chondroitin/hyaluronate hybrid scaffold. Biomaterials 27:4573–4580

    Article  Google Scholar 

  142. Uematsu K, Hattori K, Ishimoto Y, Yamauchi J, Habata T, Takakura Y et al (2005) Cartilage regeneration using mesenchymal stem cells and a three-dimensional poly-lactic-glycolic acid (PLGA) scaffold. Biomaterials 26:4273–4279

    Article  Google Scholar 

  143. Banfi A, Bianchi G, Notaro R, Luzzatto L, Cancedda R, Quarto R (2002) Replicative aging and gene expression in long-term cultures of human bone marrow stromal cells. Tissue Eng 8:901–910

    Article  Google Scholar 

  144. Parsch D, Fellenberg J, Bruemmendorf TH, Eschlbeck A-M, Richter W (2004) Telomere length and telomerase activity during expansion and differentiation of human mesenchymal stem cells and chondrocytes. J Mol Med 82:49–55

    Article  Google Scholar 

  145. Vacanti V, Kong E, Suzuki G, Sato K, Canty JM, Lee T (2005) Phenotypic changes of adult porcine mesenchymal stem cells induced by prolonged passaging in culture. J Cell Physiol 205:194–201

    Article  Google Scholar 

  146. Zhu S, Wurdak H, Wang J, Lyssiotis CA, Peters EC, Cho CY et al (2009) A small molecule primes embryonic stem cells for differentiation. Cell Stem Cell 4:416–426

    Article  Google Scholar 

  147. Wurdaka H, Zhua S, Mina KH, Aimoneb L, Lairsona LL, Watsonb J et al (2010) A small molecule accelerates neuronal differentiation in the adult rat. PNAS 107:16542–16547

    Article  Google Scholar 

  148. Richardson SM, Hoyland JA, Mobasheri R, Csaki C, Shakibaei MAM (2010) Mesenchymal stem cells in regenerative medicine: opportunities and challenges for articular cartilage and intervertebral disc tissue engineering. J Cell Physiol 222:23–32

    Article  Google Scholar 

  149. Johnstone B, Hering TM, Caplan AI, Goldberg VM, Yoo JU (1998) In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. Exp Cell Res 238:265–272

    Article  Google Scholar 

  150. Chiou MXY, Longaker MT (2006) Mitogenic and chondrogenic effects of fibroblast growth factor-2 in adipose-derived mesenchymal cells. Biochem Biophys Res Commun 343:644–652

    Article  Google Scholar 

  151. Longobardi LORL, Aakula S, Johnstone B, Shimer K, Chytil A, Horton WA, Moses HL, Spagnoli A (2006) Effect of IGF-I in the chondrogenesis of bone marrow mesenchymal stem cells in the presence or absence of TGF-beta signaling. J Bone Miner Res 21:626–636

    Article  Google Scholar 

  152. LA Solchaga PK, Porter JD, Goldberg VM, Caplan AI, Welter JF (2005) FGF-2 enhances the mitotic and chondrogenic potentials of human adult bone marrow-derived mesenchymal stem cells. J Cell Physiol 203:398–409

    Article  Google Scholar 

  153. Frenkel SR, Saadeh PB, Mehrara BJ, Steinbrech DS, Cocker RS, McCormick SA et al (1998) Transforming growth factor beta superfamily members: role in cartilage modeling. Surg Forum 49:516–518

    Google Scholar 

  154. Frenkel SR, Saadeh PB, Mehrara BJ, Chin GS, Steinbrech DS, Brent B et al (2000) Transforming growth factor beta superfamily members: role in cartilage modeling. Plast Reconstr Surg 105:980–990

    Article  Google Scholar 

  155. Van der Kan P, Vitters E, van der Berg W (1992) Differential effect of transforming growth factor beta on freshly isolated and cultured articular chondrocytes. J Rheumatol 19:140–145

    Google Scholar 

  156. Verschure PJ, Joosten LAB, Van der Kraan PM, Van der Berg WB (1994) Responsiveness of articular cartilage from normal and inflamed mouse knee joints to various growth factors. Ann Rheum Dis 53:455–460

    Article  Google Scholar 

  157. Blunk T, Sieminski AL, Gooch KJ, Courter DL, Hollander AP, Nahir M et al (2002) Differential effects of growth factors on tissue-engineered cartilage. Tissue Eng 8:73–84

    Article  Google Scholar 

  158. Sporn MB, Roberts AB, Wakefield LM, Assoian RK (1986) Transforming growth factor-β: biological function and chemical structure. Science (Washington, D C, 1883-) 233:532–534

    Google Scholar 

  159. Valcourt U, Gouttenoire J, Moustakas A, Herbage D, Mallein-Gerin F (2002) Functions of transforming growth factor-β family type I receptors and smad proteins in the hypertrophic maturation and osteoblastic differentiation of chondrocytes. J Biol Chem 277:33545–33558

    Article  Google Scholar 

  160. Pecina M, Jelic M, Martinovic S, Haspl M, Vukicevic S (2002) Articular cartilage repair: the role of bone morphogenetic proteins. Int Orthop 26:131–136

    Article  Google Scholar 

  161. Luyten FP, Yu YM, Yanagishita M, Vukicevic S, Hammonds RG, Reddi AH (1992) Natural bovine osteogenin and recombinant human bone morphogenetic protein-2B are equipotent in the maintenance of proteoglycans in bovine articular cartilage explant cultures. J Biol Chem 267:3691–3695

    Google Scholar 

  162. Mattioli-Belmonte M, Gigante A, Muzzarelli RA, Politano R, De BA, Specchia N et al (1999) N, N-dicarboxymethyl chitosan as delivery agent for bone morphogenetic protein in the repair of articular cartilage. Med Biol Eng Comput 37:130–134

    Article  Google Scholar 

  163. Kaps C, Bramlage C, Smolian H, Haisch A, Ungethum U, Burmester G-R et al (2002) Bone morphogenetic proteins promote cartilage differentiation and protect engineered artificial cartilage from fibroblast invasion and destruction. Arthritis Rheum 46:149–162

    Article  Google Scholar 

  164. Gooch KJ, Blunk T, Courter DL, Sieminski AL, Vunjak-Novakovic G, Freed LE (2002) Bone morphogenetic proteins-2, −12, and −13 modulate in vitro development of engineered cartilage. Tissue Eng 8:591–601

    Article  Google Scholar 

  165. O’Connor WJ, Botti T, Khan SN, Lane JM (2000) The use of growth factors in cartilage repair. Orthop Clin North Am 31:399–410

    Article  Google Scholar 

  166. Hunziker EB (1999) Biologic repair of articular cartilage. Defect models in experimental animals and matrix requirements. Clin Orthop Relat Res 367:S135–S146

    Article  Google Scholar 

  167. Risbud M, Endres M, Ringe J, Bhonde R, Sittinger M (2001) Biocompatible hydrogel supports the growth of respiratory epithelial cells: possibilities in tracheal tissue engineering. J Biomed Mater Res 56:120–127

    Article  Google Scholar 

  168. Boyan BD, Hummert TW, Dean DD, Schwartz Z (1996) Role of material surfaces in regulating bone and cartilage cell response. Biomaterials 17:137–146

    Article  Google Scholar 

  169. McClary KB, Ugarova T, Grainger DW (2000) Modulating fibroblast adhesion, spreading, and proliferation using self-assembled monolayer films of alkylthiolates on gold. J Biomed Mater Res 50:428–439

    Article  Google Scholar 

  170. Quirk RA, Chan WC, Davies MC, Tendler SJB, Shakesheff KM (2001) Poly(L-lysine)-GRGDS as a biomimetic surface modifier for poly(lactic acid). Biomaterials 22:865–872

    Article  Google Scholar 

  171. Chu PK, Chen JY, Wang LP, Huang N (2002) Plasma-surface modification of biomaterials. Mater Sci Eng R R36:143–206

    Article  Google Scholar 

  172. Humphries MJ, Akiyama SK, Komoriya A, Olden K, Yamada KM (1986) Identification of an alternatively spliced site in human plasma fibronectin that mediates cell type-specific adhesion. J Cell Biol 103:2637–2647

    Article  Google Scholar 

  173. Shin H, Jo S, Mikos AG (2003) Biomimetic materials for tissue engineering. Biomaterials 24:4353–4364

    Article  Google Scholar 

  174. Peppas NA, Hilt JZ, Khademhosseini A, Langer R (2006) Hydrogels in biology and medicine: from molecular principles to bionanotechnology. Adv Mater 18:1345–1360

    Article  Google Scholar 

  175. Khademhosseini A, Langer R (2007) Microengineered hydrogels for tissue engineering. Biomaterials 28:5087

    Article  Google Scholar 

  176. Nichol JW, Khademhosseini A (2009) Modular tissue engineering: engineering biological tissue from the bottom up. Soft Matter 5:1312–1319

    Article  Google Scholar 

  177. Vacanti JP, Morse MA, Saltzman WM, Domb AJ, Perez-Atayde A, Langer R (1988) Selective cell transplantation using bioabsorbable artificial polymers as matrices. J Pediatr Surg 23:3–9

    Article  Google Scholar 

  178. Mikos AG, Sarakinos G, Lyman MD, Ingber DE, Vacanti JP, Langer R (1993) Prevascularization of porous biodegradable polymers. Biotechnol Bioeng 42:716–723

    Article  Google Scholar 

  179. Annabi N, Nichol JW, Zhong X, Ji C, Koshy S, Khademhosseini A et al (2010) Controlling the porosity and microarchitecture of hydrogels for tissue engineering. Tissue Eng Part B 16:371–380

    Article  Google Scholar 

  180. Di Maio E, Mensitieri G, Iannace S, Nicolais L, Li W, Flumerfelt RW (2005) Structure optimization of polycaprolactone foams by using mixtures of CO2 and N2 as blowing agents. Polym Eng Sci 45:432–441

    Article  Google Scholar 

  181. Zhang Y, Fan W, Ma Z, Wu C, Fang W, Liu G et al (2010) The effects of pore architecture in silk fibroin scaffolds on the growth and differentiation of mesenchymal stem cells expressing BMP7. Acta Biomater 6:3021–3028

    Article  Google Scholar 

  182. Karageorgiou V, Kaplan D (2005) Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials 26:5474–5491

    Article  Google Scholar 

  183. Ngoenkam J, Faikrua A, Yasothornsrikul S, Viyoch J (2010) Potential of an injectable chitosan/starch/β-glycerol phosphate hydrogel for sustaining normal chondrocyte function. Int J Pharm 391:115–124

    Article  Google Scholar 

  184. Duncan RL, Turner CH (1995) Mechanotransduction and the functional response of bone to mechanical strain. Calcif Tissue Int 57:344–358

    Article  Google Scholar 

  185. Carter DR, Blenman PR, Beaupre GS (1988) Correlations between mechanical stress history and tissue differentiation in initial fracture healing. J Orthop Res 6:736–748

    Article  Google Scholar 

  186. Jin M, Emkey GR, Siparsky P, Trippel SB, Grodzinsky AJ (2003) Combined effects of dynamic tissue shear deformation and insulin-like growth factor I on chondrocyte biosynthesis in cartilage explants. Arch Biochem Biophys 414:223–231

    Article  Google Scholar 

  187. Hutmacher DW (2000) Scaffolds in tissue engineering bone and cartilage. Biomaterials 21:2529–2543

    Article  Google Scholar 

  188. Gerard C, Catuogno C, Amargier-Huin C, Grossin L, Hubert P, Gillet P et al (2005) The effect of alginate, hyaluronate and hyaluronate derivatives biomaterials on synthesis of non-articular chondrocyte extracellular matrix. J Mater Sci Mater Med 16:541–551

    Article  Google Scholar 

  189. Lee KY, Mooney DJ (2001) Hydrogels for tissue engineering. Chem Rev 101:1869–1879

    Article  Google Scholar 

  190. Slaughter BV, Khurshid SS, Fisher OZ, Khademhosseini A, Peppas NA (2009) Hydrogels in regenerative medicine. Adv Mater 21:3307–3329

    Article  Google Scholar 

  191. Peppas NA (1987) Hydrogels in medicine and pharmacy. CRC Press, Florida

    Google Scholar 

  192. Jabbari E (2006) Biomimetic hydrogel/apatite nanocomposite scaffolds for bone regeneration. Mater Res Soc Symp Proc 897E

    Google Scholar 

  193. Jabbari E, Nozari S (2000) Swelling behavior of acrylic acid hydrogels prepared by g-radiation crosslinking of polyacrylic acid in aqueous solution. Eur Polym J 36:2685–2692

    Article  Google Scholar 

  194. Freed LE, Marquis JC, Nohria A, Emmanual J, Mikos AG, Langer R (1993) Neocartilage formation in vitro and in vivo using cells cultured on synthetic biodegradable polymers. J Biomed Mater Res 27:11–23

    Article  Google Scholar 

  195. Liu Y, Chen F, Liu W, Cui L, Shang Q, Xia W et al (2002) Repairing large porcine full-thickness defects of articular cartilage using autologous chondrocyte-engineered cartilage. Tissue Eng 8:709–721

    Article  Google Scholar 

  196. Chu CR, Coutts RD, Yoshioka M, Harwood FL, Monosov AZ, Amiel D (1995) Articular cartilage repair using allogeneic perichondrocyte-seeded biodegradable porous polylactic acid (PLA): a tissue-engineering study. J Biomed Mater Res 29:1147–1154

    Article  Google Scholar 

  197. Vacanti CA, Langer R, Schloo B, Vacanti JP (1991) Synthetic polymers seeded with chondrocytes provide a template for new cartilage formation. Plast Reconstr Surg 88:753–759

    Article  Google Scholar 

  198. Dounchis JS, Bae WC, Chen AC, Sah RL, Coutts RD, Amiel D (2000) Cartilage repair with autogenic perichondrium cell and polylactic acid grafts. Clin Orthop Relat Res 377:248–264

    Article  Google Scholar 

  199. W-j L, Danielson KG, Alexander PG, Tuan RS (2003) Biological response of chondrocytes cultured in three-dimensional nanofibrous poly(e-caprolactone) scaffolds. J Biomed Mater Res A 67A:1105–1114

    Article  Google Scholar 

  200. Annabi N, Fathi A, Mithieux SM, Weiss AS, Dehghani F (2011) Fabrication of porous PCL/elastin composite scaffolds for tissue engineering applications. J Supercrit Fluids 59:157–167

    Article  Google Scholar 

  201. Annabi N, Fathi A, Mithieux SM, Martens P, Weiss AS, Dehghani F (2011) The effect of elastin on chondrocyte adhesion and proliferation on poly ([var epsilon]-caprolactone)/elastin composites. Biomaterials 32:1517–1525

    Article  Google Scholar 

  202. W-j L, Danielson KG, Alexander PG, Tuan RS (2003) Biological response of chondrocytes cultured in three-dimensional nanofibrous poly(ε-caprolactone) scaffolds. J Biomed Mater Res Part A 67A:1105–1114

    Article  Google Scholar 

  203. Ushio K, Oka M, Hyon S-H, Hayami T, Yura S, Matsumura K et al (2003) Attachment of artificial cartilage to underlying bone. J Biomed Mater Res Part B 68B:59–68

    Article  Google Scholar 

  204. Gu Z, Xiao J, Zhang X (1999) Development of artificial articular cartilage-PVA-hydrogel. Beijing Keji Daxue Xuebao 21:40–43

    Google Scholar 

  205. Oka M (2001) Biomechanics and repair of articular cartilage. J Orthop Sci 6:448–456

    Article  Google Scholar 

  206. Guo T, Yang T, Xiao J, Long H, Chen Y, Pei F et al (2009) Repair of articular cartilage defect in rabbits by novel biomimetic composite material of polyvinyl alcohol hydrogel/nano-hydroxyapatite + polyamide 66. Zhonghua Chuangshang Zazhi 25:748–750

    Google Scholar 

  207. Spiller KL, Liu Y, Holloway JL, Maher SA, Cao Y, Liu W et al (2012) A novel method for the direct fabrication of growth factor-loaded microspheres within porous nondegradable hydrogels: Controlled release for cartilage tissue engineering. J Control Release 157:39–45

    Article  Google Scholar 

  208. Elisseeff J, Anseth K, Sims D, McIntosh W, Randolph M, Yaremchuk M et al (1999) Transdermal photopolymerization of poly(ethylene oxide)-based injectable hydrogels for tissue-engineered cartilage. Plast Reconstr Surg 104:1014–1022

    Article  Google Scholar 

  209. Sharma B, Williams CG, Khan M, Manson P, Elisseeff JH (2006) In vivo chondrogenesis of mesenchymal stem cells in a photopolymerized hydrogel. Plast Reconstr Surg 119:112–120

    Article  Google Scholar 

  210. Hwang NS, Varghese S, Theprungsirikul P, Canver A, Elisseeff J (2006) Enhanced chondrogenic differentiation of murine embryonic stem cells in hydrogels with glucosamine. Biomaterials 27:6015–6023

    Article  Google Scholar 

  211. Nguyen QT, Hwang Y, Chen AC, Varghese S, Sah RL (2012) Cartilage-like mechanical properties of poly(ethylene glycol)-diacrylate hydrogels. Biomaterials 33:6682–6690

    Article  Google Scholar 

  212. Shung AK, Behravesh E, Jo S, Mikos AG (2003) Crosslinking characteristics of and cell adhesion to an injectable poly(propylene fumarate-co-ethylene glycol) hydrogel using a water-soluble crosslinking system. Tissue Eng 9:243–254

    Article  Google Scholar 

  213. Park H, Temenoff JS, Holland TA, Tabata Y, Mikos AG (2005) Delivery of TGF-β1 and chondrocytes via injectable, biodegradable hydrogels for cartilage tissue engineering applications. Biomaterials 26:7095–7103

    Article  Google Scholar 

  214. Sokmen N, Ayhan F, Ayhan H (2008) Gelatine containing photopolymerized poly(ethylene glycol) diacrylate hydrogels for drug delivery. Polym Prepr (Am Chem Soc, Div Polym Chem) 49:1054–1055

    Google Scholar 

  215. Drapala PW, Brey EM, Mieler WF, Venerus DC, Kang DJJ, Perez-Luna VH (2011) Role of thermo-responsiveness and poly(ethylene glycol) diacrylate cross-link density on protein release from poly(N-isopropylacrylamide) hydrogels. J Biomater Sci Polym Ed 22:59–75

    Article  Google Scholar 

  216. Holland TA, Bodde EWH, Cuijpers VMJI, Baggett LS, Tabata Y, Mikos AG et al (2007) Degradable hydrogel scaffolds for in vivo delivery of single and dual growth factors in cartilage repair. Osteoarthr Cartil 15:187–197

    Article  Google Scholar 

  217. Guo X, Park H, Liu G, Liu W, Cao Y, Tabata Y et al (2009) In vitro generation of an osteochondral construct using injectable hydrogel composites encapsulating rabbit marrow mesenchymal stem cells. Biomaterials 30:2741–2752

    Article  Google Scholar 

  218. Guo X, Park H, Young S, Kretlow JD, Van den Beucken JJ, Baggett LS et al (2010) Repair of osteochondral defects with biodegradable hydrogel composites encapsulating marrow mesenchymal stem cells in a rabbit model. Acta Biomater 6:39–47

    Article  Google Scholar 

  219. Stoltz JF, Magdalou J, Netter P, Pinzano A, Zille H, Paquet J et al (2010) Evaluation of intra-articular delivery of hyaluronic acid functionalized biopolymeric nanoparticles in healthy rat knees. Biomed Mater Eng 20:235–242

    Google Scholar 

  220. Bergsma EJ, Rozema FR, Bos RR, de Bruijn WC (1993) Foreign body reactions to resorbable poly(L-lactide) bone plates and screws used for the fixation of unstable zygomatic fractures. J Oral Maxillofac Surg 51:666–670

    Article  Google Scholar 

  221. Martin C, Winet H, Bao JY (1996) Acidity near eroding polylactide-polyglycolide in vitro and in vivo in rabbit tibial bone chambers. Biomaterials 17:2373–2380

    Article  Google Scholar 

  222. An YH, Woolf SK, Friedman RJ (2000) Pre-clinical in vivo evaluation of orthopaedic bioabsorbable devices. Biomaterials 21:2635–2652

    Article  Google Scholar 

  223. Dunn AS, Campbell PG, Marra KG (2001) The influence of polymer blend composition on the degradation of polymer/hydroxyapatite biomaterials. J Mater Sci Mater Med 12:673–677

    Article  Google Scholar 

  224. Heidemann W, Jeschkeit S, Ruffieux K, Fischer JH, Wagner M, Kruger G et al (2001) Degradation of poly(D, L)lactide implants with or without addition of calciumphosphates in vivo. Biomaterials 22:2371–2381

    Article  Google Scholar 

  225. Rezwan K, Chen QZ, Blaker JJ, Boccaccini AR (2006) Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering. Biomaterials 27:3413–3431

    Article  Google Scholar 

  226. Bazile DV, Ropert C, Huve P, Verrecchia T, Marland M, Frydman A et al (1992) Body distribution of fully biodegradable [14C]-poly(lactic acid) nanoparticles coated with albumin after parenteral administration to rats. Biomaterials 13:1093–1102

    Article  Google Scholar 

  227. Chu CR, Dounchis JS, Yoshioka M, Sah RL, Coutts RD, Amiel D (1997) Osteochondral repair using perichondrial cells. A 1-year study in rabbits. Clin Orthop Relat Res 340:220–229

    Article  Google Scholar 

  228. Xiong L, He Z (2011) Synthesis and application for porous scaffold materials of mono-methoxy polyethylene glycol/polylactide diblock copolymer. J Macromol Sci Part B Phys 50:1226–1233

    Article  Google Scholar 

  229. Pitt CG, Jeffcoat AR, Zweidinger RA, Schindler A (1979) Sustained drug delivery systems. I. The permeability of poly(ε-caprolactone), poly(DL-lactic acid), and their copolymers. J Biomed Mater Res 13:497–507

    Article  Google Scholar 

  230. Ye WP, Du FS, Jin WH, Yang JY, Xu Y (1997) In vitro degradation of poly(caprolactone), poly(lactide) and their block copolymers: influence of composition, temperature and morphology. React Funct Polym 32:161–168

    Article  Google Scholar 

  231. Coombes AGA, Verderio E, Shaw B, Li X, Griffin M, Downes S (2002) Biocomposites of non-crosslinked natural and synthetic polymers. Biomaterials 23:2113–2118

    Article  Google Scholar 

  232. Schagemann JC, Kurz H, Casper ME, Stone JS, Dadsetan M, Sun Y-L et al (2010) The effect of scaffold composition on the early structural characteristics of chondrocytes and expression of adhesion molecules. Biomaterials 31:2798–2805

    Article  Google Scholar 

  233. Park GE, Webster TJ (2005) Mechanisms of increased chondrocyte adhesion on nanometer surface featured NaOH-treated PLGA. J Biomed Nanotechnol 1:306–312

    Article  Google Scholar 

  234. Thissen H, Chang KY, Tebb TA, Tsai WB, Glattauer V, Ramshaw JAM et al (2006) Synthetic biodegradable microparticles for articular cartilage tissue engineering. J Biomed Mater Res Part A 77A:590–598

    Article  Google Scholar 

  235. Peppas NA, Merrill EW (1977) Crosslinked poly(vinyl alcohol) hydrogels as swollen elastic networks. J Appl Polym Sci Symp 21:1763–1770

    Article  Google Scholar 

  236. Amini AA, Nair LS (2012) Injectable hydrogels for bone and cartilage. Biomed Mater 7:(13pp)

    Google Scholar 

  237. Nguyen MK, Lee DS (2010) Injectable biodegradable hydrogels. Macromol Biosci 10:563–579

    Article  Google Scholar 

  238. Liu SQ, Tian Q, Hedrick JL, Hui JHP, Ee PLR, Yang YY (2010) Biomimetic hydrogels for chondrogenic differentiation of human mesenchymal stem cells to neocartilage. Biomaterials 31:7298–7307

    Article  Google Scholar 

  239. Bryant SJ, Arthur JA, Anseth KS (2005) Incorporation of tissue-specific molecules alters chondrocyte metabolism and gene expression in photocrosslinked hydrogels. Acta Biomater 1:243–252

    Article  Google Scholar 

  240. Malmonge SM, Zavaglia CA, Belangero WD (2000) Biomechanical and histological evaluation of hydrogel implants in articular cartilage. Braz J Med Biol Res 33:307–312

    Article  Google Scholar 

  241. Sawtell RM, Downes S, Kayser MV (1995) An in vitro investigation of the PEMA/THFMA system using chondrocyte culture. J Mater Sci Mater Med 6:676–679

    Article  Google Scholar 

  242. Reissis N, Kayser M, Bentley G, Downes S (1995) A hydrophylic polymer system enhanced articular cartilage regeneration in vivo. J Mater Sci Mater Med 6:768–772

    Article  Google Scholar 

  243. Bosnakovski D, Mizuno M, Kim G, Takagi S, Okumura M, Fujinaga T (2006) Chondrogenic differentiation of bovine bone marrow mesenchymal stem cells (MSCs) in different hydrogels: influence of collagen type II extracellular matrix on MSC chondrogenesis. Biotechnol Bioeng 93:1152–1163

    Article  Google Scholar 

  244. Wakitani S, Goto T, Pineda SJ, Young RG, Mansour JM, Caplan AI et al (1994) Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage. J Bone Joint Surg Am 76:579–592

    Article  Google Scholar 

  245. Harriger MD, Supp AP, Warden GD, Boyce ST (1997) Glutaraldehyde crosslinking of collagen substrates inhibits degradation in skin substitutes grafted to athymic mice. J Biomed Mater Res 35:137–145

    Article  Google Scholar 

  246. Wissink MJB, Beernink R, Poot AA, Engbers GHM, Beugeling T, Van Aken WG et al (2001) Relation between cell density and the secretion of von Willebrand factor and prostacyclin by human umbilical vein endothelial cells. Biomaterials 22:2283–2290

    Article  Google Scholar 

  247. Van LMJA, Van WPB, Olde DLHH, Dijkstra PJ, Feijen J, Nieuwenhuis P (1992) Secondary cytotoxicity of crosslinked dermal sheep collagens during repeated exposure to human fibroblasts. Biomaterials 13:1017–1024

    Article  Google Scholar 

  248. Nehrer S, Breinan HA, Ramappa A, Hsu HP, Minas T, Shortkroff S et al (1998) Chondrocyte-seeded collagen matrices implanted in a chondral defect in a canine model. Biomaterials 19:2313–2328

    Article  Google Scholar 

  249. Kon E, Delcogliano M, Filardo G, Altadonna G, Marcacci M (2009) Novel nano-composite multi-layered biomaterial for the treatment of multifocal degenerative cartilage lesions. Knee Surg Sports Traumatol Arthrosc 17:1312–1315

    Article  Google Scholar 

  250. Haisch A, Loch A, David J, Pruss A, Hansen R, Sittinger M (2000) Preparation of a pure autologous biodegradable fibrin matrix for tissue engineering. Med Biol Eng Comput 38:686–689

    Article  Google Scholar 

  251. Fortier LA, Nixon AJ, Mohammed HO, Lust G (1997) Altered biological activity of equine chondrocytes cultured in a three-dimensional fibrin matrix and supplemented with transforming growth factor β-1. Am J Vet Res 58:66–70

    Google Scholar 

  252. Li W-J, Tuan RS (2005) Polymeric scaffolds for cartilage tissue engineering. Macromol Symp 227:65–75

    Article  Google Scholar 

  253. Horan RL, Antle K, Collette AL, Wang Y, Huang J, Moreau JE et al (2005) In vitro degradation of silk fibroin. Biomaterials 26:3385–3393

    Article  Google Scholar 

  254. Qin G, Kaplan DL (2012) Silk-based biomaterials: biology, properties, and clinical applications. CRC Press, Boca Raton, pp 421–31.

    Google Scholar 

  255. Dal Pra I, Freddi G, Minic J, Chiarini A, Armato U (2005) De novo engineering of reticular connective tissue in vivo by silk fibroin nonwoven materials. Biomaterials 26:1987–1999

    Article  Google Scholar 

  256. Altman GH, Diaz F, Jakuba C, Calabro T, Horan RL, Chen J et al (2002) Silk-based biomaterials. Biomaterials 26:401–416

    Google Scholar 

  257. Mehlhorn AT, Schmal H, Kaiser S, Lepski G, Finkenzeller G, Stark GB et al (2006) Mesenchymal stem cells maintain TGF-β-mediated chondrogenic phenotype in alginate bead culture. Tissue Eng 12:1393–1403

    Article  Google Scholar 

  258. Cheng N-C, Estes BT, Awad HA, Guilak F (2009) Chondrogenic differentiation of adipose-derived adult stem cells by a porous scaffold derived from native articular cartilage extracellular matrix. Tissue Eng Part A 15:231–241

    Article  Google Scholar 

  259. Balakrishnan B, Banerjee R (2011) Biopolymer-based hydrogels for cartilage tissue engineering. Chem Rev 111:4453–4474

    Google Scholar 

  260. De Souza R, Zahedi P, Allen CJ, Piquette-Miller M (2009) Biocompatibility of injectable chitosan–phospholipid implant systems. Biomaterials 30:3818–3824

    Article  Google Scholar 

  261. Jancar J, Slovikova A, Amler E, Krupa P, Kecova H, Planka L, et al (2007) Mechanical response of porous scaffolds for cartilage engineering. Physiol Res 56:S17–S25

    Google Scholar 

  262. Medrado GCB, Machado CB, Valerio P, Sanches MD, Goes AM (2006) The effect of a chitosan-gelatin matrix and dexamethasone on the behavior of rabbit mesenchymal stem cells. Biomed Mater 1:155–161

    Google Scholar 

  263. Sa-Lima H, Caridade SG, Mano JF, Reis RL (2010) Stimuli-responsive chitosan-starch injectable hydrogels combined with encapsulated adipose-derived stromal cells for articular cartilage regeneration. Soft Matter 6:5184–5195

    Article  Google Scholar 

  264. Lippiello L (2003) Glucosamine and chondroitin sulfate: biological response modifiers of chondrocytes under simulated conditions of joint stress. Osteoarthr Cartil 11:335–342

    Article  Google Scholar 

  265. Chan PS, Caron JP, Rosa GJM, Orth MW (2005) Glucosamine and chondroitin sulfate regulate gene expression and synthesis of nitric oxide and prostaglandin E(2) in articular cartilage explants. Osteoarthr Cartil 13:387–394

    Article  Google Scholar 

  266. Uebelhart D, Thonar EJ, Delmas PD, Chantraine A, Vignon E (1998) Effects of oral chondroitin sulfate on the progression of knee osteoarthritis: a pilot study. Osteoarthr Cartil 6(Suppl A):39–46

    Article  Google Scholar 

  267. Sechriest VF, Miao YJ, Niyibizi C, Westerhausen-Larson A, Matthew HW, Evans CH et al (2000) GAG-augmented polysaccharide hydrogel: a novel biocompatible and biodegradable material to support chondrogenesis. J Biomed Mater Res 49:534–541

    Article  Google Scholar 

  268. van Susante JLC, Pieper J, Buma P, van Kuppevelt TH, van Beuningen H, van der Kraan PM et al (2001) Linkage of chondroitin-sulfate to type I collagen scaffolds stimulates the bioactivity of seeded chondrocytes in vitro. Biomaterials 22:2359–2369

    Article  Google Scholar 

  269. Betre H, Chilkoti A, Setton L. A (2002) A two step recovery system based on thermally sensitive elastin-like polypeptide scaffolds for cartilage tissue engineering. Proceedings of the Second Joint EBMS/BMES Conference pp 829–30

    Google Scholar 

  270. McHale MK, Setton LA, Chilkoti A (2006) Synthesis and in vitro evaluation of enzymatically cross-linked elastin-like polypeptide gels for cartilaginous tissue repair. Tissue Eng 11:1768–1779

    Article  Google Scholar 

  271. Ong SR, Trabbic-Carlson KA, Nettles DL, Lim DW, Chilkoti A, Setton LA (2006) Epitope tagging for tracking elastin-like polypeptides. Biomaterials 27:1930–1935

    Article  Google Scholar 

  272. Hrabchak C, Rouleau J, Moss I, Woodhouse K, Akens M, Bellingham C et al (2010) Assessment of biocompatibility and initial evaluation of genipin cross-linked elastin-like polypeptides in the treatment of an osteochondral knee defect in rabbits. Acta Biomater 6:2108–2115

    Article  Google Scholar 

  273. Stark Y, Suck K, Kasper C, Wieland M, van Griensven M, Scheper T (2006) Application of collagen matrices for cartilage tissue engineering. Exp Toxicol Pathol 57:305–311

    Article  Google Scholar 

  274. Pieper JS, van Tienen T, van Susante JLC, van der Kraan PM, Veerkamp JH et al (2003) Cross-linked type I and type II collagenous matrices for the repair of full-thickness articular cartilage defects – a study in rabbits. Biomaterials 24:3255–3263

    Article  Google Scholar 

  275. Lu HH, El-Amin SF, Scott KD, Laurencin CT (2003) Three-dimensional, bioactive, biodegradable, polymer-bioactive glass composite scaffolds with improved mechanical properties support collagen synthesis and mineralization of human osteoblast-like cells in vitro. J Biomed Mater Res A 64:465–474

    Article  Google Scholar 

  276. Nandakumar A, Fernandes H, de Boer J, Moroni L, Habibovic P, van Blitterswijk CA (2010) Fabrication of bioactive composite scaffolds by electrospinning for bone regeneration. Macromol Biosci 10:1365–1373

    Article  Google Scholar 

  277. Nowatzki PJ, Tirrell DA (2003) Physical properties of artificial extracellular matrix protein films prepared by isocyanate crosslinking. Biomaterials 25:1261–1267

    Article  Google Scholar 

  278. Nimni ME, Cheung D, Strates B, Kodama M, Sheikh K (1987) Chemically modified collagen: a natural biomaterial for tissue replacement. J Biomed Mater Res 21:741–771

    Article  Google Scholar 

  279. Sandberg LB, Soskel NT, Leslie JG (1981) Elastin structure, biosynthesis, and relation to disease states. N Engl J Med 304:566–579

    Article  Google Scholar 

  280. Nettles DL, Chilkoti A, Setton LA (2010) Applications of elastin-like polypeptides in tissue engineering. Adv Drug Deliv Rev 62:1479–1485

    Article  Google Scholar 

  281. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2002) Cell junctions, cell adhesion, and the extracellular matrix. Garland Science, New York

    Google Scholar 

  282. Daamen WF, Hafmans T, Veerkamp JH, van Kuppevelt TH (2001) Comparison of five procedures for the purification of insoluble elastin. Biomaterials 22

    Google Scholar 

  283. Partridge SM, Davis HF, Adair GS (1955) Connective tissue. II. Soluble proteins derived from partial hydrolysis of elastin. Biochem J 61:11–21

    Article  Google Scholar 

  284. Mandli I, Kellers SML (1970) Chemistry and molecular biology of the intercellular matrix. In: Balzas EA (ed) New York. Academic Press, p 665

    Google Scholar 

  285. Rnjak-Kovacina J, Daamen WF, Pierna M, Rodrı´guez-Cabello JC, Weiss AS (2011) Elastin biopolymers. In: Ducheyne P (ed) Comprehensive biomaterials. Elsevier Science, Amsterdam, pp 329–346

    Chapter  Google Scholar 

  286. Antonicelli F, Bellon G, Debelle L, Hornebeck W (2007) Elastin-elastases and inflamm-aging. Curr Top Dev Biol 79:99–155

    Article  Google Scholar 

  287. Betre H, Setton LA, Meyer DE, Chilkoti A (2002) Characterization of a genetically engineered elastin-like polypeptide for cartilaginous tissue repair. Biomacromolecules 3:910–916

    Article  Google Scholar 

  288. Betre H, Ong SR, Guilak F, Chilkoti A, Fermor B, Setton LA (2006) Chondrocytic differentiation of human adipose-derived adult stem cells in elastin-like polypeptide. Biomaterials 27:91–99

    Article  Google Scholar 

  289. Lim DW, Nettles DL, Setton LA, Chilkoti A (2007) Rapid cross-linking of elastin-like polypeptides with (Hydroxymethyl)phosphines in aqueous solution. Biomacromolecules 8:1463–1470

    Article  Google Scholar 

  290. Trabbic-Carlson K, Setton LA, Chilkoti A (2003) Swelling and mechanical behaviors of chemically cross-linked hydrogels of elastin-like polypeptides. Biomacromolecules 4:572–580

    Article  Google Scholar 

  291. Lim DW, Nettles DL, Setton LA, Chilkoti A (2008) In situ cross-linking of elastin-like polypeptide block copolymers for tissue repair. Biomacromolecules 9:222–230

    Article  Google Scholar 

  292. Annabi N, Mithieux SM, Weiss AS, Dehghani F (2010) Cross-linked open-pore elastic hydrogels based on tropoelastin, elastin and high pressure CO2. Biomaterials 31:1655–1665

    Article  Google Scholar 

  293. Nettles DL, Haider MA, Chilkoti A, Setton LA (2009) Neural network analysis identifies scaffold properties necessary for in vitro chondrogenesis in elastin-like polypeptide biopolymer scaffolds. Tissue Eng Part A 16:11–20

    Article  Google Scholar 

  294. Silverman RP, Passaretti D, Huang W, Randolph MA, Yaremchuk MJ (1999) Injectable tissue-engineered cartilage using a fibrin glue polymer. Plast Reconstr Surg 103:1809–1818

    Article  Google Scholar 

  295. Worster AA, Brower-Toland BD, Fortier LA, Bent SJ, Williams J, Nixon AJ (2001) Chondrocytic differentiation of mesenchymal stem cells sequentially exposed to transforming growth factor-β1 in monolayer and insulin-like growth factor-I in a three-dimensional matrix. J Orthop Res 19:738–749

    Article  Google Scholar 

  296. Nixon AJ, Fortier LA, Williams J, Mohammed H (1999) Enhanced repair of extensive articular defects by insulin-like growth factor-I-laden fibrin composites. J Orthop Res 17:475–487

    Article  Google Scholar 

  297. Whatley JS, Dejardin LM, Arnoczky SP (2000) The effect of an exogenous fibrin clot on the regeneration of the triangular fibrocartilage complex: an in vivo experimental study in dogs. Arthroscopy 16:127–136

    Article  Google Scholar 

  298. Paletta GA, Arnoczky SP, Warren RF (1992) The repair of osteochondral defects using an exogenous fibrin clot. An experimental study in dogs. Am J Sports Med 20:725–731

    Article  Google Scholar 

  299. van Susante JL, Buma P, Schuman L, Homminga GN, van den Berg WB, Veth RPH (1999) Resurfacing potential of heterologous chondrocytes suspended in fibrin glue in large full-thickness defects of femoral articular cartilage: an experimental study in the goat. Biomaterials 20:1167–1175

    Article  Google Scholar 

  300. Hendrickson DA, Nixon AJ, Grande DA, Todhunter RJ, Minor RM, Erb H et al (1994) Chondrocyte-fibrin matrix transplants for resurfacing extensive articular cartilage defects. J Orthop Res 12:485–497

    Article  Google Scholar 

  301. Kawabe N, Yoshinao M (1991) The repair of full-thickness articular cartilage defects. Immune responses to reparative tissue formed by allogeneic growth plate chondrocyte implants. Clin Orthop Relat Res 268:279–293

    Google Scholar 

  302. Henning CE, Lynch MA, Yearout KM, Vequist SW, Stallbaumer RJ, Decker KA (1990) Arthroscopic meniscal repair using an exogenous fibrin clot. Clin Orthop Relat Res 252:64–72

    Google Scholar 

  303. Gobin AS, Froude VE, Mathur AB (2005) Structural and mechanical characteristics of silk fibroin and chitosan blend scaffolds for tissue regeneration. J Biomed Mater Res Part A 74A:465–473

    Article  Google Scholar 

  304. Scheibel T (2006) Silk-a biomaterial with several facets. Appl Phys A Mater Sci Process 82:191–192

    Article  Google Scholar 

  305. Vepari C, Kaplan DL (2007) Silk as a biomaterial. Prog Polym Sci 32:991–1007

    Article  Google Scholar 

  306. Meinel L, Hofmann S, Karageorgiou V, Zichner L, Langer R, Kaplan D et al (2004) Engineering cartilage-like tissue using human mesenchymal stem cells and silk protein scaffolds. Biotechnol Bioeng 88:379–391

    Article  Google Scholar 

  307. Uebersax L, Merkle HP, Meinel L (2008) Insulin-like growth factor I releasing silk fibroin scaffolds induce chondrogenic differentiation of human mesenchymal stem cells. J Control Release 127:12–21

    Article  Google Scholar 

  308. Wang Y, Blasioli DJ, Kim H-J, Kim HS, Kaplan DL (2006) Cartilage tissue engineering with silk scaffolds and human articular chondrocytes. Biomaterials 27:4434–4442

    Article  Google Scholar 

  309. Wang Y, Kim U-J, Blasioli DJ, Kim H-J, Kaplan DL (2005) In vitro cartilage tissue engineering with 3D porous aqueous-derived silk scaffolds and mesenchymal stem cells. Biomaterials 26:7082–7094

    Article  Google Scholar 

  310. Hu X, Wang X, Rnjak J, Weiss AS, Kaplan DL (2010) Biomaterials derived from silk-tropoelastin protein systems. Biomaterials 31:8121–8131

    Article  Google Scholar 

  311. Hu X, Park S-H, Gil ES, Xia X-X, Weiss AS, Kaplan DL (2011) The influence of elasticity and surface roughness on myogenic and osteogenic-differentiation of cells on silk-elastin biomaterials. Biomaterials 32:8979–8989

    Article  Google Scholar 

  312. Dash M, Chiellini F, Ottenbrite RM, Chiellini E (2011) Chitosan—A versatile semi-synthetic polymer in biomedical applications. Prog Polym Sci 36:981–1014

    Article  Google Scholar 

  313. Kubota N, Tatsumoto N, Sano T, Toya K (2000) A simple preparation of half N-acetylated chitosan highly soluble in water and aqueous organic solvents. Carbohydr Res 324:268–274

    Article  Google Scholar 

  314. Lin H-Y, Chou C-C (2004) Antioxidative activities of water-soluble disaccharide chitosan derivatives. Food Res Int 37:883–889

    Article  Google Scholar 

  315. Bedekar AN, Pise AC, Thatte CS, Rathnam MV (2010) Study on optimization of carboxymethylation of chitosan obtained from squilla chitin. Asian J Chem 22:7675–7682

    Google Scholar 

  316. Gong Y, Zhu Y, Liu Y, Ma Z, Gao C, Shen J (2007) Layer-by-layer assembly of chondroitin sulfate and collagen on aminolyzed poly(L-lactic acid) porous scaffolds to enhance their chondrogenesis. Acta Biomater 3:677–685

    Article  Google Scholar 

  317. Milosavljevic NB, Milasinovic NZ, Popovic IG, Filipovic JM, Kalagasidis KMT (2011) Preparation and characterization of pH-sensitive hydrogels based on chitosan, itaconic acid and methacrylic acid. Polym Int 60:443–452

    Article  Google Scholar 

  318. Ma L, Gao C, Mao Z, Zhou J, Shen J, Hu X et al (2003) Collagen/chitosan porous scaffolds with improved biostability for skin tissue engineering. Biomaterials 24:4833–4841

    Article  Google Scholar 

  319. Shanmugasundaram N, Ravichandran P, Neelakanta RP, Ramamurty N, Pal S, Panduranga RK (2001) Collagen-chitosan polymeric scaffolds for the in vitro culture of human epidermoid carcinoma cells. Biomaterials 22:1943–1951

    Article  Google Scholar 

  320. Lu G, Kong L, Sheng B, Wang G, Gong Y, Zhang X (2007) Degradation of covalently cross-linked carboxymethyl chitosan and its potential application for peripheral nerve regeneration. Eur Polym J 43:3807–3818

    Article  Google Scholar 

  321. Ji C, Annabi N, Khademhosseini A, Dehghani F (2011) Fabrication of porous chitosan scaffolds for soft tissue engineering using dense gas CO2. Acta Biomater 7:1653–1664

    Article  Google Scholar 

  322. Ji C, Annabi N, Hosseinkhani M, Sivaloganathan S, Dehghani F (2012) Fabrication of poly-DL-lactide/polyethylene glycol scaffolds using the gas foaming technique. Acta Biomater 8:570–578

    Article  Google Scholar 

  323. Mwale F, Iordanova M, Demers CN, Steffen T, Roughley P, Antoniou J (2005) Biological evaluation of chitosan salts cross-linked to genipin as a cell scaffold for disk tissue engineering. Tissue Eng 11:130–140

    Article  Google Scholar 

  324. Ji C, Khademhosseini A, Dehghani F (2011) Enhancing cell penetration and proliferation in chitosan hydrogels for tissue engineering applications. Biomaterials 32:9719–9729

    Article  Google Scholar 

  325. Lu JX, Prudhommeaux F, Meunier A, Sedel L, Guillemin G (1999) Effects of chitosan on rat knee cartilages. Biomaterials 20:1937–1944

    Article  Google Scholar 

  326. Suh JK, Matthew HW (2000) Application of chitosan-based polysaccharide biomaterials in cartilage tissue engineering: a review. Biomaterials 21:2589–2598

    Article  Google Scholar 

  327. Shive MS, Hoemann CD, Restrepo A, Hurtig M, Duval N, Ranger P et al (2006) BST-CarGel: in situ chondroInduction for cartilage repair. Oper Tech Orthop 16:271–278

    Article  Google Scholar 

  328. Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW (1988) Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol 15:1833–1840

    Google Scholar 

  329. Seyrek E, Dubin P (2010) Glycosaminoglycans as polyelectrolytes. Adv Colloid Interface Sci 158:119–129

    Article  Google Scholar 

  330. Uebelhart D, Thonar EJ, Zhang J, Williams JM (1998) Protective effect of exogenous chondroitin 4,6-sulfate in the acute degradation of articular cartilage in the rabbit. Osteoarthr Cartil 6(Suppl A):6–13

    Article  Google Scholar 

  331. Handley CJ, Brooks P, Lowther DA (1980) Suppression of collagen synthesis by chondrocytes by exogenous concentrations of proteoglycan subunit. Biochem Int 1:270–276

    Google Scholar 

  332. Bian L, Kaplun M, Williams DY, Xu D, Ateshian GA, Hung CT (2009) Influence of chondroitin sulfate on the biochemical, mechanical and frictional properties of cartilage explants in long-term culture. J Biomech 42:286–290

    Article  Google Scholar 

  333. Varghese S, Hwang NS, Canver AC, Theprungsirikul P, Lin DW, Elisseeff J (2008) Chondroitin sulfate based niches for chondrogenic differentiation of mesenchymal stem cells. Matrix Biol 27:12–21

    Article  Google Scholar 

  334. Akmal M, Singh A, Anand A, Kesani A, Aslam N, Goodship A et al (2005) The effects of hyaluronic acid on articular chondrocytes. J Bone Joint Surg (Br) 87:1143–1149

    Article  Google Scholar 

  335. Goa KL, Benfield P (1994) Hyaluronic acid. A review of its pharmacology and use as a surgical aid in ophthalmology, and its therapeutic potential in joint disease and wound healing. Drugs 47:536–566

    Article  Google Scholar 

  336. Responte DJ, Natoli RM, Athanasiou KA (2012) Identification of potential biophysical and molecular signalling mechanisms underlying hyaluronic acid enhancement of cartilage formation. J R Soc Interface 9:3564–3573

    Article  Google Scholar 

  337. Bulpitt P, Aeschlimann D (1999) New strategy for chemical modification of hyaluronic acid: preparation of functionalized derivatives and their use in the formation of novel biocompatible hydrogels. J Biomed Mater Res 47:152–169

    Article  Google Scholar 

  338. Campoccia D, Doherty P, Radice M, Brun P, Abatangelo G, Williams DF (1998) Semisynthetic resorbable materials from hyaluronan esterification. Biomaterials 19:2101–2127

    Article  Google Scholar 

  339. Vercruysse KP, Marecak DM, Marecek JF, Prestwich GD (1997) Synthesis and in vitro degradation of new polyvalent hydrazide cross-linked hydrogels of hyaluronic acid. Bioconjug Chem 8:686–694

    Article  Google Scholar 

  340. Barbucci R, Magnani A, Rappuoli R, Lamponi S, Consumi M (2000) Immobilisation of sulphated hyaluronan for improved biocompatibility. J Inorg Biochem 79:119–125

    Article  Google Scholar 

  341. Aigner J, Tegeler J, Hutzler P, Campoccia D, Pavesio A, Hammer C et al (1998) Cartilage tissue engineering with novel nonwoven structured biomaterial based on hyaluronic acid benzyl ester. J Biomed Mater Res 42:172–181

    Article  Google Scholar 

  342. Grigolo B, Lisignoli G, Piacentini A, Fiorini M, Gobbi P, Mazzotti G et al (2001) Evidence for redifferentiation of human chondrocytes grown on a hyaluronan-based biomaterial (HYAFF11): molecular, immunohistochemical and ultrastructural analysis. Biomaterials 23:1187–1195

    Article  Google Scholar 

  343. Knudson CB (1993) Hyaluronan receptor-directed assembly of chondrocyte pericellular matrix. J Cell Biol 120:825–834

    Article  Google Scholar 

  344. Brun P, Abatangelo G, Radice M, Zacchi V, Guidolin D, Gordini DD et al (1999) Chondrocyte aggregation and reorganization into three-dimensional scaffolds. J Biomed Mater Res 46:337–346

    Article  Google Scholar 

  345. Radice M, Brun P, Cortivo R, Scapinelli R, Battaliard C, Abatangelo G (2000) Hyaluronan-based biopolymers as delivery vehicles for bone-marrow-derived mesenchymal progenitors. J Biomed Mater Res 50:101–109

    Article  Google Scholar 

  346. Solchaga LA, Dennis JE, Goldberg VM, Caplan AI (1999) Hyaluronic acid-based polymers as cell carriers for tissue-engineered repair of bone and cartilage. J Orthop Res 17:205–213

    Article  Google Scholar 

  347. Grunder T, Gaissmaier C, Fritz J, Stoop R, Hortschansky P, Mollenhauer J et al (2004) Bone morphogenetic protein (BMP)-2 enhances the expression of type II collagen and aggrecan in chondrocytes embedded in alginate beads. Osteoarthr Cartil 12:559–567

    Article  Google Scholar 

  348. Cai X, Lin Y, Ou G, Luo E, Man Y, Yuan Q et al (2007) Ectopic osteogenesis and chondrogenesis of bone marrow stromal stem cells in alginate system. Cell Biol Int 31:776–783

    Article  Google Scholar 

  349. Genes NG, Rowley JA, Mooney DJ, Bonassar LJ (2004) Effect of substrate mechanics on chondrocyte adhesion to modified alginate surfaces. Arch Biochem Biophys 422:161–167

    Article  Google Scholar 

  350. Bouhadir KH, Lee KY, Alsberg E, Damm KL, Anderson KW, Mooney DJ (2001) Degradation of partially oxidized alginate and its potential application for tissue engineering. Biotechnol Prog 17:945–950

    Article  Google Scholar 

  351. Li Y, Rodrigues J, Tomas H (2012) Injectable and biodegradable hydrogels: gelation, biodegradation and biomedical applications. Chem Soc Rev 41:2193–2221

    Article  Google Scholar 

  352. Hong Y, Gong Y, Gao C, Shen J (2008) Collagen-coated polylactide microcarriers/chitosan hydrogel composite: injectable scaffold for cartilage regeneration. J Biomed Mater Res Part A 85A:628–637

    Article  Google Scholar 

  353. Park H, Guo X, Temenoff JS, Tabata Y, Caplan AI, Kasper FK et al (2009) Effect of swelling ratio of injectable hydrogel composites on chondrogenic differentiation of encapsulated rabbit marrow mesenchymal stem cells in vitro. Biomacromolecules 10:541–546

    Article  Google Scholar 

  354. Hong Y, Song H, Gong Y, Mao Z, Gao C, Shen J (2007) Covalently crosslinked chitosan hydrogel: Properties of in vitro degradation and chondrocyte encapsulation. Acta Biomater 3:23–31

    Article  Google Scholar 

  355. Sharma B, Williams CG, Khan M, Manson P, Elisseeff JH (2007) In vivo chondrogenesis of mesenchymal stem cells in a photopolymerized hydrogel. Plast Reconstr Surg 199:112–120

    Article  Google Scholar 

  356. Villanueva I, Hauschulz DS, Mejic D, Bryant SJ (2008) Static and dynamic compressive strains influence nitric oxide production and chondrocyte bioactivity when encapsulated in PEG hydrogels of different crosslinking densities. Osteoarthr Cartil 16:909–918

    Article  Google Scholar 

  357. Nicodemus GD, Skaalure SC, Bryant SJ (2011) Gel structure has an impact on pericellular and extracellular matrix deposition, which subsequently alters metabolic activities in chondrocyte-laden PEG hydrogels. Acta Biomater 7:492–504

    Article  Google Scholar 

  358. Hou Y, Schoener CA, Regan KR, Munoz Pinto D, Hahn MS, Grunlan MA (2010) Photo-cross-linked PDMSstar-PEG hydrogels: synthesis, characterization, and potential application for tissue engineering scaffolds. Biomacromolecules 1:648–656

    Article  Google Scholar 

  359. Martens PJ, Bryant SJ, Anseth KS (2003) Tailoring the degradation of hydrogels formed from multivinyl poly(ethylene glycol) and poly(vinyl alcohol) macromers for cartilage tissue engineering. Biomacromolecules 4:283–292

    Article  Google Scholar 

  360. Nettles DL, Vail TP, Morgan MT, Grinstaff MW, Setton LA (2004) Photocrosslinkable hyaluronan as a scaffold for articular cartilage repair. Ann Biomed Eng 32:391–397

    Article  Google Scholar 

  361. Erickson IE, Huang AH, Sengupta S, Kestle S, Burdick JA, Mauck RL (2009) Macromer density influences mesenchymal stem cell chondrogenesis and maturation in photocrosslinked hyaluronic acid hydrogels. Osteoarthr Cartil 17:1639–1648

    Article  Google Scholar 

  362. Jeon O, Bouhadir KH, Mansour JM, Alsberg E (2009) Photocrosslinked alginate hydrogels with tunable biodegradation rates and mechanical properties. Biomaterials 30:2724–2734

    Article  Google Scholar 

  363. Nichol JW, Koshy ST, Bae H, Hwang CM, Yamanlar S, Khademhosseini A (2010) Cell-laden microengineered gelatin methacrylate hydrogels. Biomaterials 31:5536–5544

    Article  Google Scholar 

  364. Hu X, Ma L, Wang C, Gao C (2009) Gelatin hydrogel prepared by photo-initiated polymerization and loaded with TGF-β1 for cartilage tissue engineering. Macromol Biosci 9:1194–1201

    Article  Google Scholar 

  365. Tan H, Rubin JP, Marra KG (2010) Injectable in situ forming biodegradable chitosan-hyaluronic acid based hydrogels for adipose tissue regeneration. Organogenesis 6:173–180

    Article  Google Scholar 

  366. Jin R, Moreira TLS, Dijkstra PJ, van Blitterswijk CA, Karperien M, Feijen J (2010) Enzymatically-crosslinked injectable hydrogels based on biomimetic dextran-hyaluronic acid conjugates for cartilage tissue engineering. Biomaterials 31:3103–3113

    Article  Google Scholar 

  367. Tran NQ, Joung YK, Lih E, Park KM, Park KD (2010) Supramolecular hydrogels exhibiting fast in situ gel forming and adjustable degradation properties. Biomacromolecules 11:617–625

    Article  Google Scholar 

  368. Hu P, Xu B (2003) Injectable hydrogel scaffold for cartilage tissue engineering. Tsinghua University, People’s Republic of China, p 6

    Google Scholar 

  369. Ko DY, Shinde UP, Yeon B, Jeong B (2010) Recent progress on in situ formed gels for biomedical applications. Prog Polym Sci

    Google Scholar 

  370. Sharma D, George P, Button PD, May BK, Kasapis S (2011) Thermomechanical study of the phase behaviour of agarose/gelatin mixtures in the presence of glucose syrup as co-solute. Food Chem 127:1784–1791

    Article  Google Scholar 

  371. Li Q, Williams CG, Sun DDN, Wang J, Leong K, Elisseeff JH (2003) Photocrosslinkable polysaccharides based on chondroitin sulfate. J Biomed Mater Res Part A 68A:28–33

    Article  Google Scholar 

  372. Habibovic P, Juhl MV, Clyens S, Martinetti R, Dolcini L, Theilgaard N et al (2010) Comparison of two carbonated apatite ceramics in vivo. Acta Biomater 6:2219–2226

    Article  Google Scholar 

  373. Kim M, Kim SE, Kang SS, Kim YH, Tae G (2011) The use of de-differentiated chondrocytes delivered by a heparin-based hydrogel to regenerate cartilage in partial-thickness defects. Biomaterials 32:7883–7896

    Article  Google Scholar 

  374. Lee J, Choi WI, Tae G, Kim YH, Kang SS, Kim SE et al (2011) Enhanced regeneration of the ligament–bone interface using a poly(l-lactide–co-ε-caprolactone) scaffold with local delivery of cells/BMP-2 using a heparin-based hydrogel. Acta Biomater 7:244–257

    Article  Google Scholar 

  375. Zhang J, Skardal A, Prestwich GD (2008) Engineered extracellular matrices with cleavable crosslinkers for cell expansion and easy cell recovery. Biomaterials 29:4521–4531

    Article  Google Scholar 

  376. Davis NE, Ding S, Forster RE, Pinkas DM, Barron AE (2010) Modular enzymatically crosslinked protein polymer hydrogels for in situ gelation. Biomaterials 31:7288–7297

    Article  Google Scholar 

  377. Yang Z, Liang G, Xu B (2007) Enzymatic control of the self-assembly of small molecules: a new way to generate supramolecular hydrogels. Soft Matter 3:515–520

    Article  Google Scholar 

  378. Chen T, Embree HD, Brown EM, Taylor MM, Payne GF (2003) Enzyme-catalyzed gel formation of gelatin and chitosan: potential for in situ applications. Biomaterials 24:2831–2841

    Article  Google Scholar 

  379. Toledano S, Williams RJ, Jayawarna V, Ulijn RV (2006) Enzyme-triggered self-assembly of peptide hydrogels via reversed hydrolysis. J Am Chem Soc 128:1070–1071

    Article  Google Scholar 

  380. Burke MD, Park JO, Srinivasarao M, Khan SA (2005) A novel enzymatic technique for limiting drug mobility in a hydrogel matrix. J Control Release 104:141–153

    Article  Google Scholar 

  381. Hughes M, Xu H, Frederix PWJM, Smith AM, Hunt NT, Tuttle T et al (2011) Biocatalytic self-assembly of 2D peptide-based nanostructures. Soft Matter 7:10032–10038

    Article  Google Scholar 

  382. Hoare T, Pelton R (2004) Functional group distributions in carboxylic acid containing poly(N-isopropylacrylamide) microgels. Langmuir 20:2123–2133

    Article  Google Scholar 

  383. Jones JA, Novo N, Flagler K, Pagnucco CD, Carew S, Cheong C et al (2005) Thermoresponsive copolymers of methacrylic acid and poly(ethylene glycol) methyl ether methacrylate. J Polym Sci A Polym Chem 43:6095–6104

    Article  Google Scholar 

  384. Han CK, Bae YH (1998) Inverse thermally-reversible gelation of aqueous N-isopropylacrylamide copolymer solutions. Polymer 39:2809–2814

    Article  Google Scholar 

  385. Chen G, Hoffman AS (1995) Graft copolymers that exhibit temperature-induced phase transitions over a wide range of pH. Nature 373:49–52

    Article  Google Scholar 

  386. Schilli CM, Zhang M, Rizzardo E, Thang SH, Chong YK, Edwards K et al (2004) A new double-responsive block copolymer synthesized via RAFT polymerization: poly(N-isopropylacrylamide)-block-poly(acrylic acid). Macromolecules 37:7861–7866

    Article  Google Scholar 

  387. Garbern JC, Hoffman AS, Stayton PS (2010) Injectable pH- and temperature-responsive poly(N-isopropylacrylamide-co-propylacrylic acid) copolymers for delivery of angiogenic growth factors. Biomacromolecules 11:1833–1839

    Article  Google Scholar 

  388. Pollock JF, Healy KE (2010) Mechanical and swelling characterization of poly(N-isopropyl acrylamide-comethoxy poly(ethylene glycol) methacrylate) sol-gels. Acta Biomater 6:1307–1318

    Article  Google Scholar 

  389. Yun K, Moon HT (2008) Inducing chondrogenic differentiation in injectable hydrogels embedded with rabbit chondrocytes and growth factor for neocartilage formation. J Biosci Bioeng 105:122–126

    Article  Google Scholar 

  390. Huang X, Zhang Y, Donahue HJ, Lowe TL (2007) Porous thermoresponsive-co-biodegradable hydrogels as tissue-engineering scaffolds for 3-dimensional in vitro culture of chondrocytes. Tissue Eng 13:2645–2652

    Article  Google Scholar 

  391. Sa-Lima H, Tuzlakoglu K, Mano JF, Reis RL (2011) Thermoresponsive poly(N-isopropylacrylamide)-g-methylcellulose hydrogel as a three-dimensional extracellular matrix for cartilage-engineered applications. J Biomed Mater Res Part A 98A:596–603

    Article  Google Scholar 

  392. Lue S, Liu M, Ni B (2011) Degradable, injectable poly(N-isopropylacrylamide)-based hydrogels with low gelation concentrations for protein delivery application. Chem Eng J 173:241–250

    Google Scholar 

  393. Haider M, Cappello J, Ghandehari H, Leong K (2008) In vitro chondrogenesis of mesenchymal stem cells in recombinant silk-elastinlike hydrogels. Pharm Res 25:692–699

    Article  Google Scholar 

  394. Guan J, Hong Y, Ma Z, Wagner WR (2008) Protein-reactive, thermoresponsive copolymers with high flexibility and biodegradability. Biomacromolecules 9:1283–1292

    Article  Google Scholar 

  395. Cho J, Heuzey MC, Bégin A, Carreau PJ (2005) Physical gelation of chitosan in the presence of beta-glycerophosphate: the effect of temperature. Biomacromolecules 6:3267–3275

    Article  Google Scholar 

  396. Chenite A, Chaput C, Wang D, Combes C, Buschmann MD, Hoemann CD et al (2000) Novel injectable neutral solutions of chitosan form biodegradable gels in situ. Biomaterials 21:2155–2161

    Article  Google Scholar 

  397. Park KM, Lee SY, Joung YK, Na JS, Lee MC, Park KD (2009) Thermosensitive chitosan-pluronic hydrogel as an injectable cell delivery carrier for cartilage regeneration. Acta Biomater 5:1956–1965

    Article  Google Scholar 

  398. Abe M, Takahashi M, Tokura S, Tamura H, Nagano A (2004) Cartilage-scaffold composites produced by bioresorbable beta-chitin sponge with cultured rabbit chondrocytes. Tissue Eng 10:585–594

    Article  Google Scholar 

  399. Iwasaki N, Kasahara Y, Yamane S, Igarashi T, Minami A, Nisimura S-i (2011) Chitosan-based hyaluronic acid hybrid polymer fibers as a scaffold biomaterial for cartilage tissue engineering. Polymers 3:100–113

    Google Scholar 

  400. Liu Y, Lu W-L, Wang J-C, Zhang X, Zhang H, Wang X-Q et al (2007) Controlled delivery of recombinant hirudin based on thermo-sensitive Pluronic F127 hydrogel for subcutaneous administration: in vitro and in vivo characterization. J Control Release 117:387–395

    Article  Google Scholar 

  401. Cohn D, Lando G, Sosnik A, Garty S, Levi A (2006) PEO-PPO-PEO-based poly(ether ester urethane)s as degradable reverse thermo-responsive multiblock copolymers. Biomaterials 27:1718–1727

    Article  Google Scholar 

  402. Jeong B, Bae YH, Kim SW (2000) In situ gelation of PEG-PLGA-PEG triblock copolymer aqueous solutions and degradation thereof. J Biomed Mater Res 50:171–177

    Article  Google Scholar 

  403. de las Alarcon CH, Pennadam S, Alexander C (2005) Stimuli responsive polymers for biomedical applications. Chem Soc Rev 34:276–285

    Article  Google Scholar 

  404. Heskins M, Guillet JE (1968) Solution properties of poly(N-isopropylacrylamide). J Macromol Sci Chem A2:1441

    Google Scholar 

  405. Ha DI, Lee SB, Chong MS, Lee YM (2006) Preparation of thermo-responsive and injectable hydrogels based on hyaluronic acid and poly(N-isopropylacrylamide) and their drug release behaviors. Macromol Res 14:87–93

    Article  Google Scholar 

  406. Cappello JCJ, Dorman M, Mikolajczak M, Textor G, Marquet M, Ferrari F (1990) Genetic engineering of structural protein polymers. Biotechnol Prog 6:198–202

    Article  Google Scholar 

  407. Nettles DL, Vali TP, Flahiff CM, Walkenhorst J, Carter AJ, Setton LA (2005) Injectable silk-elastin for articular cartilage defect repair. Trans of the ORS Washington, DC, p 1366

    Google Scholar 

  408. Hoemann CD, Sun J, Légaré A, McKee MD, Buschmann MD (2005) Tissue engineering of cartilage using an injectable and adhesive chitosan-based cell-delivery vehicle. Osteoarthr Cartil 13:318–329

    Article  Google Scholar 

  409. Ruel-Gariépy E, Shive M, Bichara A, Berrada M, Le Garrec D, Chenite A et al (2004) A thermosensitive chitosan-based hydrogel for the local delivery of paclitaxel. Eur J Pharm Biopharm 57:53–63

    Article  Google Scholar 

  410. Li Z, Zhang M (2005) Chitosan–alginate as scaffolding material for cartilage tissue engineering. J Biomed Mater Res A 75A:485–493

    Article  Google Scholar 

  411. Yamane S, Iwasaki N, Majima T, Funakoshi T, Masuko T, Harada K et al (2005) Feasibility of chitosan-based hyaluronic acid hybrid biomaterial for a novel scaffold in cartilage tissue engineering. Biomaterials 26:611–619

    Article  Google Scholar 

  412. Chen Y-L, Lee H-P, Chan H-Y, Sung L-Y, Chen H-C, Hu Y-C (2007) Composite chondroitin-6-sulfate/dermatan sulfate/chitosan scaffolds for cartilage tissue engineering. Biomaterials 28:2294–2305

    Article  Google Scholar 

  413. Jung HH, Park K, Han DK (2010) Preparation of TGF-β1-conjugated biodegradable pluronic F127 hydrogel and its application with adipose-derived stem cells. J Control Release 147:84–91

    Article  Google Scholar 

  414. Safran CB, Farach-Carson MC, Jia X, Srinivasan PP, Jha A (2012) Injectable delivery system for heparan sulfate-binding growth factors. University of Delaware, USA, p 30

    Google Scholar 

  415. Dell’Accio F, Vanlauwe J, Bellemans J, Neys J, de Bari C, Luyten FP (2003) Expanded phenotypically stable chondrocytes persist in the repair tissue and contribute to cartilage matrix formation and structural integration in a goat model of autologous chondrocyte implantation. J Orthop Res 21:123–131

    Article  Google Scholar 

  416. Grande DA, Pitman MI, Peterson L, Menche D, Klein M (1989) The repair of experimentally produced defects in rabbit articular cartilage by autologous chondrocyte transplantation. J Orthop Res 7:208–218

    Article  Google Scholar 

  417. Miot S, de Freitas PS, Wirz D, Daniels AU, Sims TJ, Hollander AP, Mainil-Varlet P et al (2006) Cartilage tissue engineering by expanded goat articular chondrocytes. J Orthop Res 24(5):1078–1085

    Article  Google Scholar 

  418. Martin I, Obradovic B, Treppo S, Grodzinsky AJ, Langer R, Freed LE et al (2000) Modulation of the mechanical properties of tissue engineered cartilage. Biorheology 31:1–2

    Google Scholar 

  419. Bugbee WD, Convery FR (1999) Osteochondral allograft transplantation. Clin Sports Med 18:67–75

    Article  Google Scholar 

  420. Hangody L, Feczkó P, Bartha L, Bodó G, Kish G (2001) Mosaicplasty for the treatment of articular defects of the knee and ankle. Clin Orthop Relat Res 391:S328–S336

    Article  Google Scholar 

  421. Steadman JR, Rodkey WG, Singleton SB, Briggs KK (1997) Microfracture technique for full-thickness chondral defects: technique and clinical results. Oper Tech Orthop 7:300–304

    Article  Google Scholar 

  422. Johnson LL (2001) Arthroscopic abrasion arthroplasty: a review. Clin Orthop Relat Res 391:S306–S317

    Article  Google Scholar 

  423. Hoemann C, Sun J, McKee M, Hurtig M, Rivard GE, Rossomacha E, et al (2005) Rabbit hyaline cartilage repair after marrow stimulation depends on the surgical approach together with an in situ stabilized chitosan-GP blood clot. Transactions 11th Canadian connective tissue conference, 1372

    Google Scholar 

  424. Hoemann CD, Hurtig M, Rossomacha E, Sun J, Chevrier A, Shive MS et al (2005) Chitosan-glycerol phosphate/blood implants improve hyaline cartilage repair in ovine microfracture defects. J Bone Joint Surg Am 87:2671–2686

    Google Scholar 

  425. Gobbi A, Kon E, Berruto M, Francisco R, Filardo G, Marcacci M (2006) Patellofemoral full-thickness chondral defects treated with Hyalograft-C: a clinical, arthroscopic, and histologic review. Am J Sports Med 34:1763–1773

    Article  Google Scholar 

  426. Benedetti L, Cortivo R, Berti T, Berti A, Pea F, Mazzo M et al (1993) Biocompatibility and biodegradation of different hyaluronan derivatives (Hyaff) implanted in rats. Biomaterials 14:1154–1160

    Article  Google Scholar 

  427. Girotto D, Urbani S, Brun P, Renier D, Barbucci R, Abatangelo G (2003) Tissue-specific gene expression in chondrocytes grown on three-dimensional hyaluronic acid scaffolds. Biomaterials 24:3265–3275

    Article  Google Scholar 

  428. Marcacci M, Berruto M, Brocchetta D, Delcogliano A, Ghinelli D, Gobbi A et al (2005) Articular cartilage engineering with Hyalograft C: 3-year clinical results. Clin Orthop Relat Res 435:96–105

    Article  Google Scholar 

  429. Nehrer S, Domayer S, Dorotka R, Schatz K, Bindreiter U, Kotz R (2006) Three-year clinical outcome after chondrocyte transplantation using a hyaluronan matrix for cartilage repair. Eur J Radiol 57:3–8

    Article  Google Scholar 

  430. Weidenbecher M, Henderson JH, Tucker HM, Baskin JZ, Awadallah A, Dennis JE (2007) Hyaluronan-based scaffolds to tissue-engineer cartilage implants for laryngotracheal reconstruction. Laryngoscope 117:1745–1749

    Article  Google Scholar 

  431. Schneider U, Rackwitz L, Andereya S, Siebenlist S, Fensky F, Reichert J et al (2011) A prospective multicenter study on the outcome of type I collagen hydrogel-based autologous chondrocyte implantation (CaReS) for the repair of articular cartilage defects in the knee. Am J Sports Med 39:2558–2565

    Article  Google Scholar 

  432. Welsch GH, Mamisch TC, Zak L, Blanke M, Olk A, Marlovits S et al (2010) Evaluation of cartilage repair tissue after matrix-associated autologous chondrocyte transplantation using a hyaluronic-based or a collagen-based scaffold with morphological MOCART scoring and biochemical T2 mapping: preliminary results. Am J Sports Med 38:934–942

    Article  Google Scholar 

  433. Carmont MR, Carey-Smith R, Saithna A, Dhillon M, Thompson P, Spalding T (2009) Delayed incorporation of a TruFit plug: perseverance is recommended. Arthroscopy 25:810–814

    Article  Google Scholar 

  434. Melton JTK, Wilson AJ, Chapman-Sheath P, Cossey AJ (2010) TruFit CB bone plug: chondral repair, scaffold design, surgical technique and early experiences. Expert Rev Med Devices 7:333–341

    Article  Google Scholar 

  435. Kerker JT, Leo AJ, Sgaglione NA (2008) Cartilage repair: synthetics and scaffolds: basic science, surgical techniques, and clinical outcomes. Sports Med Arthrosc 16:208–216

    Article  Google Scholar 

  436. McNickle AG, Provencher MT, Cole BJ (2008) Overview of existing cartilage repair technology. Sports Med Arthrosc 16:196–201

    Article  Google Scholar 

  437. Joshi N, Reverte-Vinaixa M, Diaz-Ferreiro EW, Dominguez-Oronoz R (2012) Synthetic resorbable scaffolds for the treatment of isolated patellofemoral cartilage defects in young patients: magnetic resonance imaging and clinical evaluation. Am J Sports Med 40:1289–1295

    Article  Google Scholar 

  438. Crawford DC, Heveran CM, Cannon WD Jr, Foo LF, Potter HG (2009) An autologous cartilage tissue implant NeoCart for treatment of grade III chondral injury to the distal femur: prospective clinical safety trial at 2 years. Am J Sports Med 37:1334–1343

    Article  Google Scholar 

  439. Kim HT, Zaffagnini S, Mizuno S, Abelow S, Safran MR (2006) A peek into the possible future of management of articular cartilage injuries: gene therapy and scaffolds for cartilage repair. J Orthop Sports Phys Ther 36:765–773

    Article  Google Scholar 

  440. Hoemann CD, Sun J, McKee MD, Chevrier A, Rossomacha E, Rivard GE et al (2006) Chitosan-glycerol phosphate/blood implants elicit hyaline cartilage repair integrated with porous subchondral bone in microdrilled rabbit defects. Osteoarthr Cartil 15:78–89(Epub 2006 Aug 8)

    Google Scholar 

  441. Buschmann MD, Hoemann CD, Hurtig MB (2006) Cartilage repair: analysis and strategies. In: William RJ (ed) Cartilage repair with chitosan/glycerol-phosphate stabilised blood clots. Totowa Human Press, Totowa, pp 83–106

    Google Scholar 

  442. Grigolo B, Lisignoli G, Piacentini A, Fiorini M, Gobbi P, Mazzotti G et al (2002) Evidence for redifferentiation of human chondrocytes grown on a hyaluronan-based biomaterial (HYAff 11): molecular, immunohistochemical and ultrastructural analysis. Biomaterials 23:1187–1195

    Article  Google Scholar 

  443. Pavesio A, Abatangelo G, Borrione A, Brocchetta D, Hollander AP, Kon E et al (2003) Hyaluronan-based scaffolds (Hyalograft C) in the treatment of knee cartilage defects: preliminary clinical findings. Novartis Found Symp 249:203–17; discussion 29–33, 34–8, 39–41

    Google Scholar 

  444. Nehrer S, Dorotka R, Domayer S, Stelzeneder D, Kotz R (2009) Treatment of full-thickness chondral defects with hyalograft C in the knee: a prospective clinical case series with 2 to 7 years’ follow-up. Am J Sports Med 37(Suppl 1):81S–87S

    Article  Google Scholar 

  445. Kon E, Di MA, Filardo G, Tetta C, Busacca M, Iacono F et al (2011) Second-generation autologous chondrocyte transplantation: MRI findings and clinical correlations at a minimum 5-year follow-up. Eur J Radiol 79:382–388

    Article  Google Scholar 

  446. Marcacci M, Zaffagnini S, Kon E, Visani A, Iacono F, Loreti I (2002) Arthroscopic autologous chondrocyte transplantation: technical note. Knee Surg Sports Traumatol Arthrosc 10:154–159

    Article  Google Scholar 

  447. Henderson I, Lavigne P, Valenzuela H, Oakes B (2007) Autologous chondrocyte implantation: superior biologic properties of hyaline cartilage repairs. Clin Orthop Relat Res 455:253–261

    Article  Google Scholar 

  448. Knutsen G, Drogset JO, Engebretsen L, Grontvedt T, Isaksen V, Ludvigsen TC et al (2007) A randomized trial comparing autologous chondrocyte implantation with microfracture. Findings at five years. J Bone Joint Surg Am 89:2105–2112

    Google Scholar 

  449. Cole BJ (2008) A randomized trial comparing autologous chondrocyte implantation with microfracture. J Bone Joint Surg Am 90:1165; author reply −6

    Google Scholar 

  450. Dhollander AAM, Liekens K, Almqvist KF, Verdonk R, Lambrecht S, Elewaut D et al (2012) 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 28:225–233

    Article  Google Scholar 

  451. Safran MR, Kim H, Zaffagnini S (2008) The use of scaffolds in the management of articular cartilage injury. J Am Acad Orthop Surg 16:306–311

    Article  Google Scholar 

  452. Weng Y, Cao Y, Silva CA, Vacanti MP, Vacanti CA (2001) Tissue-engineered composites of bone and cartilage for mandible condylar reconstruction. J Oral Maxillofac Surg 59:185–190

    Article  Google Scholar 

  453. Sharma B, Fermanian S, Gibson M, Unterman S, Herzka DA, Cascio B et al (2013) Human cartilage repair with a photoreactive adhesive-hydrogel composite. Sci Transl Med 5:167ra6, 10 pp

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Chemical and Biomolecular Engineering, The University of Sydney, Sydney, NSW, 2006, Australia

    Fariba Dehghani & Ali Fathi

Authors
  1. Fariba Dehghani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ali Fathi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fariba Dehghani .

Editor information

Editors and Affiliations

  1. School of Aerospace, Mechanical & Mechatronic Engineering, The University of Sydney, Sydney, New South Wales, Australia

    Qing Li

  2. School of Aerospace, Mechanical & Mechatronic Engineering, The University of Sydney, Sydney, New South Wales, Australia

    Yiu-Wing Mai

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer-Verlag GmbH Germany

About this chapter

Cite this chapter

Dehghani, F., Fathi, A. (2017). Challenges for Cartilage Regeneration. In: Li, Q., Mai, YW. (eds) Biomaterials for Implants and Scaffolds. Springer Series in Biomaterials Science and Engineering, vol 8. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-53574-5_14

Download citation

Publish with us

Policies and ethics

Search

Navigation