The Archives of Bone and Joint Surgery

The Archives of Bone and Joint Surgery

Biochemical Aspects of Scaffolds for Cartilage Tissue Engineering; from Basic Science to Regenerative Medicine

Document Type : CURRENT CONCEPTS REVIEW

Authors
Davood Yari 1
Mohammad H. Ebrahimzadeh 2
Jebrail Movaffagh 3
Azadeh Shahroodi 3
Moein Shirzad 4
Durdi Qujeq 4
Ali Moradi 2
1 1 Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran. 2 Department of Clinical Biochemistry, Babol University of Medical Sciences, Babol, Iran 3 Orthopedic Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
2 Orthopedic Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
3 Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
4 Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran. 2 Department of Clinical Biochemistry, Babol University of Medical Sciences, Babol, Iran
10.22038/abjs.2022.55549.2766
Abstract
Chondral defects are frequent and important causes of pain and disability. Cartilage has limited self-repair and 
regeneration capacity. The ideal approach for articular cartilage defects is the regeneration of hyaline cartilage with 
sustainable symptom-free constructs. Tissue engineering provides new strategies for the regeneration of functional 
cartilage tissue through optimized scaffolds with architectural, mechanical, and biochemical properties similar to the 
native cartilage tissue. In this review, the basic science of cartilage structure, interactions between proteins, stem cells, 
as well as biomaterials, scaffold characteristics and fabrication methods, as well as current and potential therapies in 
regenerative medicine will be discussed mostly from a biochemical point of view. Furthermore, the recent trends in 
scaffold-based therapies and supplementary factors in cartilage tissue engineering will be considered. 
Level of evidence: I
Keywords
Biochemical
Cartilage
Cartilage regeneration
Scaffold
Tissue engineering
  1. Casanellas I, Garcia-Lizarribar A, Lagunas A, Samitier J. Producing 3D Biomimetic Nanomaterials for Musculoskeletal System Regeneration. Front Bioeng Biotechnol. 2018;6:128.
  2. Hunziker EB, Quinn TM, Hauselmann HJ. Quantitative structural organization of normal adult human articular cartilage. Osteoarthritis Cartilage. 2002; 10(7):564-72.
  3. Murphy L, Helmick CG. The impact of osteoarthritis in the United States: a population-health perspective: A population-based review of the fourth most common cause of hospitalization in U.S. adults. Orthop Nurs. 2012;31(2):85-91.
  4. Vilela CA, da Silva Morais A, Pina S, Oliveira JM, Correlo VM, Reis RL, et al. Clinical Trials and Management of Osteochondral Lesions. Adv Exp Med Biol. 2018;1058:391-413.
  5. Bicho D, Pina S, Reis RL, Oliveira JM. Commercial Products for Osteochondral Tissue Repair and Regeneration. Adv Exp Med Biol. 2018;1058:415-28.
  6. Buckwalter JA, Mankin HJ. Articular cartilage: degeneration and osteoarthritis, repair, regeneration, and transplantation. Instr Course Lect. 1998;47:487-504.
  7. Buckwalter JA, Mankin HJ. Articular cartilage: tissue design and chondrocyte-matrix interactions. Instr Course Lect. 1998;47:477-86.
  8. Camp CL, Stuart MJ, Krych AJ. Current concepts of articular cartilage restoration techniques in the knee. Sports Health. 2014;6(3):265-73.
  9. Gudas R, Gudaite A, Mickevicius T, Masiulis N, Simonaityte R, Cekanauskas E, et al. Comparison of osteochondral autologous transplantation, microfracture, or debridement techniques in articular cartilage lesions associated with anterior cruciate ligament injury: a prospective study with a 3-year follow-up. Arthroscopy. 2013;29(1):89-97.
  10. Richter DL, Schenck RC, Jr., Wascher DC, Treme G. Knee Articular Cartilage Repair and Restoration Techniques: A Review of the Literature. Sports Health. 2016;8(2):153-60.
  11. Oliver-Welsh L, Griffin JW, Meyer MA, Gitelis ME, Cole BJ. Deciding How Best to Treat Cartilage Defects. Orthopedics. 2016;39(6):343-50.
  12. Mason C, Dunnill P. A brief definition of regenerative medicine. Regen Med. 2008;3(1):1-5.
  13. Decker RS. Articular cartilage and joint development from embryogenesis to adulthood. InSeminars in cell & developmental biology 2017 (Vol. 62, pp. 50-56). Academic Press.
  14. Zhang L, Hu J, Athanasiou KA. The role of tissue engineering in articular cartilage repair and regeneration. Crit Rev Biomed Eng. 2009;37(1-2):1-57.
  15. Jorgensen AEM, Kjaer M, Heinemeier KM. The Effect of Aging and Mechanical Loading on the Metabolism of Articular Cartilage. J Rheumatol. 2017;44(4):410-7.
  16. Elder BD, Athanasiou KA. Hydrostatic pressure in articular cartilage tissue engineering: from chondrocytes to tissue regeneration. Tissue Eng Part B Rev. 2009;15(1):43-53.
  17. Zhu M, Li W, Dong X, Yuan X, Midgley AC, Chang H, et al. In vivo engineered extracellular matrix scaffolds with instructive niches for oriented tissue regeneration. Nature communications. 2019;10(1):1-4.
  18. Sundelacruz S, Kaplan DL. Stem cell-and scaffold-based tissue engineering approaches to osteochondral regenerative medicine. InSeminars in cell & developmental biology 2009 (Vol. 20, No. 6, pp. 646-655). Academic Press..
  19. Humphrey JD, Dufresne ER, Schwartz MA. Mechanotransduction and extracellular matrix homeostasis. Nat Rev Mol Cell Biol. 2014;15(12):802-12.
  20. Alford JW, Cole BJ. Cartilage restoration, part 1: basic science, historical perspective, patient evaluation, and treatment options. Am J Sports Med. 2005;33(2):295-306.
  21. Patel JM, Wise BC, Bonnevie ED, Mauck RL. A Systematic Review and Guide to Mechanical Testing for Articular Cartilage Tissue Engineering. Tissue Eng Part C Methods. 2019;25(10):593-608.
  22. Yamashita A, Tamamura Y, Morioka M, Karagiannis P, Shima N, Tsumaki N. Considerations in hiPSC-derived cartilage for articular cartilage repair. Inflammation and Regeneration. 2018;38(1):1-7..
  23. Tatari H. The structure, physiology, and biomechanics of articular cartilage: injury and repair. Acta orthopaedica et traumatologica turcica. 2007;41:1-5.
  24. Yari D, Ehsanbakhsh Z, Validad MH, Langroudi FH. Association of TIMP-1 and COL4A4 Gene Polymorphisms with Keratoconus in an Iranian Population. J Ophthalmic Vis Res. 2020;15(3):299-307.
  25. Moradi A, Ataollahi F, Sayar K, Pramanik S, Chong PP, Khalil AA, et al. Chondrogenic potential of physically treated bovine cartilage matrix derived porous scaffolds on human dermal fibroblast cells. J Biomed Mater Res A. 2016;104(1):245-56.
  26. Mehlhorn AT, Niemeyer P, Kaiser S, Finkenzeller G, Stark GB, Sudkamp NP, et al. Differential expression pattern of extracellular matrix molecules during chondrogenesis of mesenchymal stem cells from bone marrow and adipose tissue. Tissue Eng. 2006;12(10):2853-62.
  27. Vincent TL, Wann AK. Mechanoadaptation: articular cartilage through thick and thin. The Journal of physiology. 2019;597(5):1271-81..
  28. Roughley PJ, Lee ER. Cartilage proteoglycans: structure and potential functions. Microsc Res Tech. 1994;28(5):385-97.
  29. Sarrazin S, Lamanna WC, Esko JD. Heparan sulfate proteoglycans. Cold Spring Harbor perspectives in biology. 2011;3(7):a004952.
  30. Neves MI, Araújo M, Moroni L, da Silva RM, Barrias CC. Glycosaminoglycan-inspired biomaterials for the development of bioactive hydrogel networks. Molecules. 2020;25(4):978.
  31. Iozzo RV, Schaefer L. Proteoglycan form and function: A comprehensive nomenclature of proteoglycans. Matrix Biol. 2015;42:11-55.
  32. Driessen BJH, Logie C, Vonk LA. Cellular reprogramming for clinical cartilage repair. Cell Biol Toxicol. 2017;33(4):329-49.
  33. Wilusz RE, Sanchez-Adams J, Guilak F. The structure and function of the pericellular matrix of articular cartilage. Matrix Biol. 2014;39:25-32.
  34. Carballo CB, Nakagawa Y, Sekiya I, Rodeo SA. Basic Science of Articular Cartilage. Clin Sports Med. 2017;36(3):413-25.
  35. Bolton MC, Dudhia J, Bayliss MT. Age-related changes in the synthesis of link protein and aggrecan in human articular cartilage: implications for aggregate stability. Biochem J. 1999;337(1):77-82.
  36. Price JS, Waters JG, Darrah C, Pennington C, Edwards DR, Donell ST, et al. The role of chondrocyte senescence in osteoarthritis. Aging Cell. 2002;1(1):57-65.
  37. Saravani R, Yari D, Saravani S, Hasanian-Langroudi F. Correlation between the COL4A3, MMP-9, and TIMP-1 polymorphisms and risk of keratoconus. Jpn J Ophthalmol. 2017;61(3):218-22.
  38. Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med. 1994;331(14):889-95.
  39. Lepperdinger G, Brunauer R, Jamnig A, Laschober G, Kassem M. Controversial issue: is it safe to employ mesenchymal stem cells in cell-based therapies? Exp Gerontol. 2008;43(11):1018-23.
  40. Mendelson A, Frank E, Allred C, Jones E, Chen M, Zhao W, et al. Chondrogenesis by chemotactic homing of synovium, bone marrow, and adipose stem cells in vitro. FASEB J. 2011;25(10):3496-504.
  41. Lo Monaco M, Merckx G, Ratajczak J, Gervois P, Hilkens P, Clegg P, et al. Stem Cells for Cartilage Repair: Preclinical Studies and Insights in Translational Animal Models and Outcome Measures. Stem Cells Int. 2018;2018:9079538.
  42. Wang M, Yuan Z, Ma N, Hao C, Guo W, Zou G, et al. Advances and Prospects in Stem Cells for Cartilage Regeneration. Stem Cells Int. 2017;2017:4130607.
  43. Jacob G, Shimomura K, Krych AJ, Nakamura N. The Meniscus Tear: A Review of Stem Cell Therapies. Cells. 2019;9(1).
  44. Gur-Cohen S, Yang H, Baksh SC, Miao Y, Levorse J, Kataru RP, et al. Stem cell-driven lymphatic remodeling coordinates tissue regeneration. Science. 2019;366(6470):1218-25.
  45. Wang WG, Lou SQ, Ju XD, Xia K, Xia JH. In vitro chondrogenesis of human bone marrow-derived mesenchymal progenitor cells in monolayer culture: activation by transfection with TGF-beta2. Tissue Cell. 2003;35(1):69-77.
  46. Caplan AI. Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J Cell Physiol. 2007;213(2):341-7.
  47. Mahmoudifar N, Doran PM. Chondrogenic differentiation of human adipose-derived stem cells in polyglycolic acid mesh scaffolds under dynamic culture conditions. Biomaterials. 2010;31(14):3858-67.
  48. Pievani A, Scagliotti V, Russo FM, Azario I, Rambaldi B, Sacchetti B, et al. Comparative analysis of multilineage properties of mesenchymal stromal cells derived from fetal sources shows an advantage of mesenchymal stromal cells isolated from cord blood in chondrogenic differentiation potential. Cytotherapy. 2014;16(7):893-905.
  49. Wang SJ, Jiang D, Zhang ZZ, Huang AB, Qi YS, Wang HJ, et al. Chondrogenic Potential of Peripheral Blood Derived Mesenchymal Stem Cells Seeded on Demineralized Cancellous Bone Scaffolds. Sci Rep. 2016;6:36400.
  50. Zuliani CC, Bombini MF, Andrade KC, Mamoni R, Pereira AH, Coimbra IB. Micromass cultures are effective for differentiation of human amniotic fluid stem cells into chondrocytes. Clinics (Sao Paulo). 2018;73:e268.
  51. Longoni A, Utomo L, van Hooijdonk IE, Bittermann GK, Vetter VC, Kruijt Spanjer EC, et al. The chondrogenic differentiation potential of dental pulp stem cells. Eur Cell Mater. 2020;39:121-35.
  52. To K, Zhang B, Romain K, Mak C, Khan W. Synovium-Derived Mesenchymal Stem Cell Transplantation in Cartilage Regeneration: A PRISMA Review of in vivo Studies. Front Bioeng Biotechnol. 2019;7:314.
  53. Andriamanalijaona R, Duval E, Raoudi M, Lecourt S, Vilquin JT, Marolleau JP, et al. Differentiation potential of human muscle-derived cells towards chondrogenic phenotype in alginate beads culture. Osteoarthritis Cartilage. 2008;16(12):1509-18.
  54. Huang JI, Kazmi N, Durbhakula MM, Hering TM, Yoo JU, Johnstone B. Chondrogenic potential of progenitor cells derived from human bone marrow and adipose tissue: a patient-matched comparison. J Orthop Res. 2005;23(6):1383-9.
  55. Contentin R, Demoor M, Concari M, Desance M, Audigie F, Branly T, et al. Comparison of the Chondrogenic Potential of Mesenchymal Stem Cells Derived from Bone Marrow and Umbilical Cord Blood Intended for Cartilage Tissue Engineering. Stem Cell Rev Rep. 2020;16(1):126-43.
  56. Silva JC, Udangawa RN, Chen J, Mancinelli CD, Garrudo FFF, Mikael PE, et al. Kartogenin-loaded coaxial PGS/PCL aligned nanofibers for cartilage tissue engineering. Mater Sci Eng C Mater Biol Appl. 2020;107:110291.
  57. Moura CS, Silva JC, Faria S, Fernandes PR, da Silva CL, Cabral JMS, et al. Chondrogenic differentiation of mesenchymal stem/stromal cells on 3D porous poly (epsilon-caprolactone) scaffolds: Effects of material alkaline treatment and chondroitin sulfate supplementation. J Biosci Bioeng. 2020;129(6):756-64.
  58. Kohli N, Wright KT, Sammons RL, Jeys L, Snow M, Johnson WE. An In Vitro Comparison of the Incorporation, Growth, and Chondrogenic Potential of Human Bone Marrow versus Adipose Tissue Mesenchymal Stem Cells in Clinically Relevant Cell Scaffolds Used for Cartilage Repair. Cartilage. 2015;6(4):252-63.
  59. Satue M, Schuler C, Ginner N, Erben RG. Intra-articularly injected mesenchymal stem cells promote cartilage regeneration, but do not permanently engraft in distant organs. Sci Rep. 2019;9(1):10153.
  60. Secunda R, Vennila R, Mohanashankar AM, Rajasundari M, Jeswanth S, Surendran R. Isolation, expansion and characterisation of mesenchymal stem cells from human bone marrow, adipose tissue, umbilical cord blood and matrix: a comparative study. Cytotechnology. 2015;67(5):793-807.
  61. Baghaei K, Hashemi SM, Tokhanbigli S, Asadi Rad A, Assadzadeh-Aghdaei H, Sharifian A, et al. Isolation, differentiation, and characterization of mesenchymal stem cells from human bone marrow. Gastroenterol Hepatol Bed Bench. 2017;10(3):208-13.
  62. Grskovic B, Ruzicka K, Karimi A, Qujeq D, Muller MM. Cell cycle analysis of the CD133+ and CD133- cells isolated from umbilical cord blood. Clin Chim Acta. 2004;343(1-2):173-8.
  63. Park D, Lim J, Park JY, Lee SH. Concise Review: Stem Cell Microenvironment on a Chip: Current Technologies for Tissue Engineering and Stem Cell Biology. Stem Cells Transl Med. 2015;4(11):1352-68.
  64. Jansen KA, Donato DM, Balcioglu HE, Schmidt T, Danen EH, Koenderink GH. A guide to mechanobiology: Where biology and physics meet. Biochim Biophys Acta. 2015;1853(11 Pt B):3043-52.
  65. Kim IG, Gil CH, Seo J, Park SJ, Subbiah R, Jung TH, et al. Mechanotransduction of human pluripotent stem cells cultivated on tunable cell-derived extracellular matrix. Biomaterials. 2018;150:100-11.
  66. Johnson VL, Hunter DJ. The epidemiology of osteoarthritis. Best Pract Res Clin Rheumatol. 2014;28(1):5-15.
  67. Hattori T, Muller C, Gebhard S, Bauer E, Pausch F, Schlund B, et al. SOX9 is a major negative regulator of cartilage vascularization, bone marrow formation and endochondral ossification. Development. 2010;137(6):901-11.
  68. Schnabel M, Marlovits S, Eckhoff G, Fichtel I, Gotzen L, Vecsei V, et al. Dedifferentiation-associated changes in morphology and gene expression in primary human articular chondrocytes in cell culture. Osteoarthritis Cartilage. 2002;10(1):62-70.
  69. Zou J, Bai B, Yao Y. Progress of Co-culture Systems in Cartilage Regeneration. Expert Opin Biol Ther. 2018;18(11):1151-8.
  70. Benya PD, Shaffer JD. Dedifferentiated chondrocytes reexpress the differentiated collagen phenotype when cultured in agarose gels. Cell. 1982;30(1):215-24.
  71. Okubo R, Asawa Y, Watanabe M, Nagata S, Nio M, Takato T, et al. Proliferation medium in three-dimensional culture of auricular chondrocytes promotes effective cartilage regeneration in vivo. Regen Ther. 2019;11:306-15.
  72. Jin GZ, Kim HW. Efficacy of collagen and alginate hydrogels for the prevention of rat chondrocyte dedifferentiation. J Tissue Eng. 2018;9:2041731418802438.
  73. Puetzer JL, Petitte JN, Loboa EG. Comparative review of growth factors for induction of three-dimensional in vitro chondrogenesis in human mesenchymal stem cells isolated from bone marrow and adipose tissue. Tissue Eng Part B Rev. 2010;16(4):435-44.
  74. Schumann D, Kujat R, Nerlich M, Angele P. Mechanobiological conditioning of stem cells for cartilage tissue engineering. Biomed Mater Eng. 2006;16(4 Suppl):S37-52.
  75. Zhang S, Vijayavenkataraman S, Lu WF, Fuh JYH. A review on the use of computational methods to characterize, design, and optimize tissue engineering scaffolds, with a potential in 3D printing fabrication. J Biomed Mater Res B Appl Biomater. 2019;107(5):1329-51.
  76. Jafari M, Paknejad Z, Rad MR, Motamedian SR, Eghbal MJ, Nadjmi N, et al. Polymeric scaffolds in tissue engineering: a literature review. J Biomed Mater Res B Appl Biomater. 2017;105(2):431-59.
  77. Chai Q, Jiao Y, Yu X. Hydrogels for Biomedical Applications: Their Characteristics and the Mechanisms behind Them. Gels. 2017;3(1).
  78. Bordbar S, Lotfi Bakhshaiesh N, Khanmohammadi M, Sayahpour FA, Alini M, Baghaban Eslaminejad M. Production and evaluation of decellularized extracellular matrix hydrogel for cartilage regeneration derived from knee cartilage. J Biomed Mater Res A. 2020;108(4):938-46.
  79. Thompson WR, Scott A, Loghmani MT, Ward SR, Warden SJ. Understanding Mechanobiology: Physical Therapists as a Force in Mechanotherapy and Musculoskeletal Regenerative Rehabilitation. Phys Ther. 2016;96(4):560-9.
  80. Marrella A, Lee TY, Lee DH, Karuthedom S, Syla D, Chawla A, et al. Engineering vascularized and innervated bone biomaterials for improved skeletal tissue regeneration. Mater Today (Kidlington). 2018;21(4):362-76.
  81. Hersel U, Dahmen C, Kessler H. RGD modified polymers: biomaterials for stimulated cell adhesion and beyond. Biomaterials. 2003;24(24):4385-415.
  82. Amann E, Wolff P, Breel E, van Griensven M, Balmayor ER. Hyaluronic acid facilitates chondrogenesis and matrix deposition of human adipose derived mesenchymal stem cells and human chondrocytes co-cultures. Acta Biomater. 2017;52:130-44.
  83. Cheng A, Schwartz Z, Kahn A, Li X, Shao Z, Sun M, et al. Advances in Porous Scaffold Design for Bone and Cartilage Tissue Engineering and Regeneration. Tissue Eng Part B Rev. 2019;25(1):14-29.
  84. Liu W, Thomopoulos S, Xia Y. Electrospun nanofibers for regenerative medicine. Adv Healthc Mater. 2012;1(1):10-25.
  85. Amiri N, Rozbeh Z, Afrough T, Sajadi Tabassi SA, Moradi A, Movaffagh J. Optimization of Chitosan-Gelatin Nanofibers Production: Investigating the Effect of Solution Properties and Working Parameters on Fibers Diameter. BioNanoScience. 2018;8(3):778-89.
  86. Amiri N, Moradi A, Tabasi SAS, Movaffagh J. Modeling and process optimization of electrospinning of chitosan-collagen nanofiber by response surface methodology. Materials Research Express. 2018; 5(4):045404.
  87. Braghirolli DI, Steffens D, Pranke P. Electrospinning for regenerative medicine: a review of the main topics. Drug Discov Today. 2014;19(6):743-53.
  88. Kundu B, Rajkhowa R, Kundu SC, Wang X. Silk fibroin biomaterials for tissue regenerations. Adv Drug Deliv Rev. 2013;65(4):457-70.
  89. Friess W. Collagen--biomaterial for drug delivery. Eur J Pharm Biopharm. 1998;45(2):113-36.
  90. Ma PX, Zhang R. Synthetic nano-scale fibrous extracellular matrix. J Biomed Mater Res. 1999;46(1):60-72.
  91. Garcia Y, Wilkins B, Collighan RJ, Griffin M, Pandit A. Towards development of a dermal rudiment for enhanced wound healing response. Biomaterials. 2008;29(7):857-68.
  92. Movaffagh J, Fazly Bazzaz BS, Yazdi AT, Sajadi-Tabassi A, Azizzadeh M, Najafi E, et al. Wound Healing and Antimicrobial Effects of Chitosan-hydrogel/Honey Compounds in a Rat Full-thickness Wound Model. Wounds. 2019;31(9):228-35.
  93. Stokols S, Tuszynski MH. Freeze-dried agarose scaffolds with uniaxial channels stimulate and guide linear axonal growth following spinal cord injury. Biomaterials. 2006;27(3):443-51.
  94. Bozkurt A, Lassner F, O’Dey D, Deumens R, Bocker A, Schwendt T, et al. The role of microstructured and interconnected pore channels in a collagen-based nerve guide on axonal regeneration in peripheral nerves. Biomaterials. 2012;33(5):1363-75.
  95. Ghassemi T, Saghatolslami N, Matin MM, Gheshlaghi R, Moradi A. CNT-decellularized cartilage hybrids for tissue engineering applications. Biomed Mater. 2017;12(6):065008.
  96. Rowland CR, Lennon DP, Caplan AI, Guilak F. The effects of crosslinking of scaffolds engineered from cartilage ECM on the chondrogenic differentiation of MSCs. Biomaterials. 2013;34(23):5802-12.
  97. Shen W, Chen X, Hu Y, Yin Z, Zhu T, Hu J, et al. Long-term effects of knitted silk-collagen sponge scaffold on anterior cruciate ligament reconstruction and osteoarthritis prevention. Biomaterials. 2014;35(28):8154-63.
  98. Qujeq D, Abassi R, Faeizi F, Parsian H, Faraji AS, Taheri H, et al. Effect of granulocyte colony-stimulating factor administration on tissue regeneration due to carbon tetrachloride-induced liver damage in experimental model. Toxicol Ind Health. 2013;29(6):498-503.
  99. Drury JL, Mooney DJ. Hydrogels for tissue engineering: scaffold design variables and applications. Biomaterials. 2003;24(24):4337-51.
  100. Zhou Y, Liang K, Zhao S, Zhang C, Li J, Yang H, et al. Photopolymerized maleilated chitosan/methacrylated silk fibroin micro/nanocomposite hydrogels as potential scaffolds for cartilage tissue engineering. Int J Biol Macromol. 2018;108:383-90.
  101. Burdick JA, Chung C, Jia X, Randolph MA, Langer R. Controlled degradation and mechanical behavior of photopolymerized hyaluronic acid networks. Biomacromolecules. 2005;6(1):386-91.
  102. Joanne P, Kitsara M, Boitard SE, Naemetalla H, Vanneaux V, Pernot M, et al. Nanofibrous clinical-grade collagen scaffolds seeded with human cardiomyocytes induces cardiac remodeling in dilated cardiomyopathy. Biomaterials. 2016;80:157-68.
  103. Miao Z, Lu Z, Wu H, Liu H, Li M, Lei D, et al. Collagen, agarose, alginate, and Matrigel hydrogels as cell substrates for culture of chondrocytes in vitro: A comparative study. J Cell Biochem. 2017.
  104. Stoppel WL, Ghezzi CE, McNamara SL, Black LD, 3rd, Kaplan DL. Clinical applications of naturally derived biopolymer-based scaffolds for regenerative medicine. Ann Biomed Eng. 2015;43(3):657-80.
  105. Chan G, Mooney DJ. New materials for tissue engineering: towards greater control over the biological response. Trends Biotechnol. 2008;26(7):382-92.
  106. Cheng CW, Solorio LD, Alsberg E. Decellularized tissue and cell-derived extracellular matrices as scaffolds for orthopaedic tissue engineering. Biotechnol Adv. 2014;32(2):462-84.
  107. Morris AH, Stamer DK, Kyriakides TR. The host response to naturally-derived extracellular matrix biomaterials. Semin Immunol. 2017;29:72-91.
  108. Hoshiba T, Lu H, Kawazoe N, Chen G. Decellularized matrices for tissue engineering. Expert Opin Biol Ther. 2010;10(12):1717-28.
  109. Gupta SK, Mishra NC, Dhasmana A. Decellularization Methods for Scaffold Fabrication. Methods Mol Biol. 2018;1577:1-10.
  110. Kim YS, Majid M, Melchiorri AJ, Mikos AG. Applications of decellularized extracellular matrix in bone and cartilage tissue engineering. Bioeng Transl Med. 2019;4(1):83-95.
  111. Johnson TD, Hill RC, Dzieciatkowska M, Nigam V, Behfar A, Christman KL, et al. Quantification of decellularized human myocardial matrix: A comparison of six patients. Proteomics Clin Appl. 2016;10(1):75-83.
  112. Sanchez PL, Fernandez-Santos ME, Costanza S, Climent AM, Moscoso I, Gonzalez-Nicolas MA, et al. Acellular human heart matrix: A critical step toward whole heart grafts. Biomaterials. 2015;61:279-89.
  113. VeDepo MC, Buse EE, Quinn RW, Williams TD, Detamore MS, Hopkins RA, et al. Species-specific effects of aortic valve decellularization. Acta Biomater. 2017;50:249-58.
  114. Pellegata AF, Asnaghi MA, Stefani I, Maestroni A, Maestroni S, Dominioni T, et al. Detergent-enzymatic decellularization of swine blood vessels: insight on mechanical properties for vascular tissue engineering. Biomed Res Int. 2013;2013:918753.
  115. Ghassemi T, Saghatoleslami N, Mahdavi-Shahri N, Matin MM, Gheshlaghi R, Moradi A. A comparison study of different decellularization treatments on bovine articular cartilage. J Tissue Eng Regen Med. 2019;13(10):1861-71.
  116. Moradi A, Pramanik S, Ataollahi F, Abdul Khalil A, Kamarul T, Pingguan-Murphy B. A comparison study of different physical treatments on cartilage matrix derived porous scaffolds for tissue engineering applications. Sci Technol Adv Mater. 2014;15(6):065001.
  117. Garrigues NW, Little D, Sanchez-Adams J, Ruch DS, Guilak F. Electrospun cartilage-derived matrix scaffolds for cartilage tissue engineering. J Biomed Mater Res A. 2014;102(11):3998-4008.
  118. Cheng NC, Estes BT, Young TH, Guilak F. Genipin-crosslinked cartilage-derived matrix as a scaffold for human adipose-derived stem cell chondrogenesis. Tissue Eng Part A. 2013;19(3-4):484-96.
  119. Cheng NC, Estes BT, Young TH, Guilak F. Engineered cartilage using primary chondrocytes cultured in a porous cartilage-derived matrix. Regen Med. 2011;6(1):81-93.
  120. Mao Y, Block T, Singh-Varma A, Sheldrake A, Leeth R, Griffey S, et al. Extracellular matrix derived from chondrocytes promotes rapid expansion of human primary chondrocytes in vitro with reduced dedifferentiation. Acta Biomater. 2019;85:75-83.
  121. Fermor HL, McLure SW, Taylor SD, Russell SL, Williams S, Fisher J, et al. Biological, biochemical and biomechanical characterisation of articular cartilage from the porcine, bovine and ovine hip and knee. Biomed Mater Eng. 2015;25(4):381-95.
  122. Taylor SD, Tsiridis E, Ingham E, Jin Z, Fisher J, Williams S. Comparison of human and animal femoral head chondral properties and geometries. Proc Inst Mech Eng H. 2012;226(1):55-62.
  123. Palmese LL, Thapa RK, Sullivan MO, Kiick KL. Hybrid hydrogels for biomedical applications. Curr Opin Chem Eng. 2019;24:143-57.
  124. Grover GN, Rao N, Christman KL. Myocardial matrix-polyethylene glycol hybrid hydrogels for tissue engineering. Nanotechnology. 2014;25(1):014011.
  125. Mansour JM, Welter JF. Multimodal evaluation of tissue-engineered cartilage. J Med Biol Eng. 2013;33(1):1-16.
  126. Zhou S, Wang Y, Zhang K, Cao N, Yang R, Huang J, et al. The Fabrication and Evaluation of a Potential Biomaterial Produced with Stem Cell Sheet Technology for Future Regenerative Medicine. Stem Cells Int. 2020;2020:9567362.
  127. Vincourt JB, Lionneton F, Kratassiouk G, Guillemin F, Netter P, Mainard D, et al. Establishment of a reliable method for direct proteome characterization of human articular cartilage. Mol Cell Proteomics. 2006;5(10):1984-95.
  128. De Ceuninck F, Marcheteau E, Berger S, Caliez A, Dumont V, Raes M, et al. Assessment of some tools for the characterization of the human osteoarthritic cartilage proteome. J Biomol Tech. 2005;16(3):256-65.
  129. Gaudet AD, Popovich PG. Extracellular matrix regulation of inflammation in the healthy and injured spinal cord. Exp Neurol. 2014;258:24-34.
  130. Acharya C, Yik JH, Kishore A, Van Dinh V, Di Cesare PE, Haudenschild DR. Cartilage oligomeric matrix protein and its binding partners in the cartilage extracellular matrix: interaction, regulation and role in chondrogenesis. Matrix Biol. 2014;37:102-11.
  131. Oh CD, Lu Y, Liang S, Mori-Akiyama Y, Chen D, de Crombrugghe B, et al. SOX9 regulates multiple genes in chondrocytes, including genes encoding ECM proteins, ECM modification enzymes, receptors, and transporters. PLoS One. 2014;9(9):e107577.
  132. Tew SR, Clegg PD, Brew CJ, Redmond CM, Hardingham TE. SOX9 transduction of a human chondrocytic cell line identifies novel genes regulated in primary human chondrocytes and in osteoarthritis. Arthritis Res Ther. 2007;9(5):R107.
  133. Henry SP, Liang S, Akdemir KC, de Crombrugghe B. The postnatal role of Sox9 in cartilage. J Bone Miner Res. 2012;27(12):2511-25.
  134. Kim Y, Murao H, Yamamoto K, Deng JM, Behringer RR, Nakamura T, et al. Generation of transgenic mice for conditional overexpression of Sox9. J Bone Miner Metab. 2011;29(1):123-9.
  135. Taheem DK, Foyt DA, Loaiza S, Ferreira SA, Ilic D, Auner HW, et al. Differential Regulation of Human Bone Marrow Mesenchymal Stromal Cell Chondrogenesis by Hypoxia Inducible Factor-1alpha Hydroxylase Inhibitors. Stem Cells. 2018;36(9):1380-92.
  136. Jahr H, Gunes S, Kuhn AR, Nebelung S, Pufe T. Bioreactor-Controlled Physoxia Regulates TGF-beta Signaling to Alter Extracellular Matrix Synthesis by Human Chondrocytes. Int J Mol Sci. 2019;20(7).
  137. Markway BD, Cho H, Johnstone B. Hypoxia promotes redifferentiation and suppresses markers of hypertrophy and degeneration in both healthy and osteoarthritic chondrocytes. Arthritis Res Ther. 2013;15(4):R92.
  138. Schrobback K, Malda J, Crawford RW, Upton Z, Leavesley DI, Klein TJ. Effects of oxygen on zonal marker expression in human articular chondrocytes. Tissue Eng Part A. 2012;18(9-10):920-33.
  139. Milner PI, Wilkins RJ, Gibson JS. The role of mitochondrial reactive oxygen species in pH regulation in articular chondrocytes. Osteoarthritis Cartilage. 2007;15(7):735-42.
  140. Yari D, Saravani R, Saravani S, Ebrahimian K, Galavi HR. Genetic Polymorphisms of Catalase and Glutathione Peroxidase-1 in Keratoconus. Iran J Public Health. 2018;47(10):1567-74.
  141. Das RH, van Osch GJ, Kreukniet M, Oostra J, Weinans H, Jahr H. Effects of individual control of pH and hypoxia in chondrocyte culture. J Orthop Res. 2010;28(4):537-45.
  142. Mitchell AC, Briquez PS, Hubbell JA, Cochran JR. Engineering growth factors for regenerative medicine applications. Acta Biomater. 2016;30:1-12.
  143. Belair DG, Le NN, Murphy WL. Design of growth factor sequestering biomaterials. Chem Commun (Camb). 2014;50(99):15651-68.
  144. Thielen NGM, van der Kraan PM, van Caam APM. TGFbeta/BMP Signaling Pathway in Cartilage Homeostasis. Cells. 2019;8(9).
  145. Xu X, Zheng L, Yuan Q, Zhen G, Crane JL, Zhou X, et al. Transforming growth factor-beta in stem cells and tissue homeostasis. Bone Res. 2018;6:2.
  146. Coricor G, Serra R. TGF-beta regulates phosphorylation and stabilization of Sox9 protein in chondrocytes through p38 and Smad dependent mechanisms. Sci Rep. 2016;6:38616.
  147. Badlani N, Oshima Y, Healey R, Coutts R, Amiel D. Use of bone morphogenic protein-7 as a treatment for osteoarthritis. Clin Orthop Relat Res. 2009;467(12):3221-9.
  148. Shi S, Mercer S, Eckert GJ, Trippel SB. Regulation of articular chondrocyte catabolic genes by growth factor interaction. J Cell Biochem. 2019;120(7):11127-39.
  149. Shi S, Mercer S, Eckert GJ, Trippel SB. Growth factor transgenes interactively regulate articular chondrocytes. J Cell Biochem. 2013;114(4):908-19.
  150. Li J, Dong S. The Signaling Pathways Involved in Chondrocyte Differentiation and Hypertrophic Differentiation. Stem Cells Int. 2016;2016:2470351.
  151. Wang Y, Fan X, Xing L, Tian F. Wnt signaling: a promising target for osteoarthritis therapy. Cell Commun Signal. 2019;17(1):97.
  152. Gao Y, Liu S, Huang J, Guo W, Chen J, Zhang L, et al. The ECM-cell interaction of cartilage extracellular matrix on chondrocytes. Biomed Res Int. 2014;2014:648459.
  153. Mas-Moruno C, Fraioli R, Rechenmacher F, Neubauer S, Kapp TG, Kessler H. alphavbeta3- or alpha5beta1-Integrin-Selective Peptidomimetics for Surface Coating. Angew Chem Int Ed Engl. 2016;55(25):7048-67.
  154. Jansen KA, Atherton P, Ballestrem C. Mechanotransduction at the cell-matrix interface. Semin Cell Dev Biol. 2017;71:75-83.
  155. Hu X, Margadant FM, Yao M, Sheetz MP. Molecular stretching modulates mechanosensing pathways. Protein Sci. 2017;26(7):1337-51.
  156. Johnstone B, Alini M, Cucchiarini M, Dodge GR, Eglin D, Guilak F, et al. Tissue engineering for articular cartilage repair--the state of the art. Eur Cell Mater. 2013;25:248-67.
  157. Di Bella C, Duchi S, O’Connell CD, Blanchard R, Augustine C, Yue Z, et al. In situ handheld three-dimensional bioprinting for cartilage regeneration. J Tissue Eng Regen Med. 2018;12(3):611-21.
  158. Khan IM, Gilbert SJ, Singhrao SK, Duance VC, Archer CW. Cartilage integration: evaluation of the reasons for failure of integration during cartilage repair. A review. Eur Cell Mater. 2008;16:26-39.
  159. Yang YH, Ard MB, Halper JT, Barabino GA. Type I collagen-based fibrous capsule enhances integration of tissue-engineered cartilage with native articular cartilage. Ann Biomed Eng. 2014;42(4):716-26.
  160. Pabbruwe MB, Esfandiari E, Kafienah W, Tarlton JF, Hollander AP. Induction of cartilage integration by a chondrocyte/collagen-scaffold implant. Biomaterials. 2009;30(26):4277-86.
  161. Yang YK, Ogando CR, Barabino GA. In Vitro Evaluation of the Influence of Substrate Mechanics on Matrix-Assisted Human Chondrocyte Transplantation. J Funct Biomater. 2020;11(1).
  162. Gurusinghe S, Strappe P. Gene modification of mesenchymal stem cells and articular chondrocytes to enhance chondrogenesis. Biomed Res Int. 2014;2014:369528.
  163. Celik E, Bayram C, Denkbas EB. Chondrogenesis of human mesenchymal stem cells by microRNA loaded triple polysaccharide nanoparticle system. Mater Sci Eng C Mater Biol Appl. 2019;102:756-63.
  164. Jimenez G, Venkateswaran S, Lopez-Ruiz E, Peran M, Pernagallo S, Diaz-Monchon JJ, et al. A soft 3D polyacrylate hydrogel recapitulates the cartilage niche and allows growth-factor free tissue engineering of human articular cartilage. Acta Biomater. 2019;90:146-56.
  165. Takada E, Mizuno S. Reproduction of Characteristics of Extracellular Matrices in Specific Longitudinal Depth Zone Cartilage within Spherical Organoids in Response to Changes in Osmotic Pressure. Int J Mol Sci. 2018;19(5).
  166. Yeung P, Cheng KH, Yan CH, Chan BP. Collagen microsphere based 3D culture system for human osteoarthritis chondrocytes (hOACs). Sci Rep. 2019;9(1):12453.
  167. Udomluck N, Kim SH, Cho H, Park JY, Park H. Three-dimensional cartilage tissue regeneration system harnessing goblet-shaped microwells containing biocompatible hydrogel. Biofabrication. 2019;12(1):015019.
  168. Saraswat R, Ratnayake I, Perez EC, Schutz WM, Zhu Z, Ahrenkiel SP, et al. Micropatterned Biphasic Nanocomposite Platform for Maintaining Chondrocyte Morphology. ACS Appl Mater Interfaces. 2020;12(13):14814-24.
  169. Yan X, Chen YR, Song YF, Yang M, Ye J, Zhou G, et al. Scaffold-Based Gene Therapeutics for Osteochondral Tissue Engineering. Front Pharmacol. 2019;10:1534.
  170. Cong L, Zhu Y, Tu G. A bioinformatic analysis of microRNAs role in osteoarthritis. Osteoarthritis Cartilage. 2017;25(8):1362-71.
  171. Wolock SL, Krishnan I, Tenen DE, Matkins V, Camacho V, Patel S, et al. Mapping Distinct Bone Marrow Niche Populations and Their Differentiation Paths. Cell Rep. 2019;28(2):302-11 e5.
  172. Huynh N, Kelly N, Katz D, Pham M, Guilak F. Single Cell RNA Sequencing Reveals Heterogeneity of Human MSC Chondrogenesis: Lasso Regularized Logistic Regression to Identify Gene and Regulatory Signatures. bioRxiv. 2019:854406
  173. Zhang B, Gao L, Ma L, Luo Y, Yang H, Cui Z. 3D Bioprinting: A Novel Avenue for Manufacturing Tissues and Organs. Engineering. 2019;5(4):777-94.
  174. Derby B. Printing and prototyping of tissues and scaffolds. Science. 2012;338(6109):921-6.
  175. Henrionnet C, Pourchet L, Neybecker P, Messaoudi O, Gillet P, Loeuille D, et al. Combining Innovative Bioink and Low Cell Density for the Production of 3D-Bioprinted Cartilage Substitutes: A Pilot Study. Stem Cells International. 2020;2020:1-16.
  176. Francis SL, Di Bella C, Wallace GG, Choong PFM. Cartilage Tissue Engineering Using Stem Cells and Bioprinting Technology-Barriers to Clinical Translation. Front Surg. 2018;5:70.
  177. Ruiz-Cantu L, Gleadall A, Faris C, Segal J, Shakesheff K, Yang J. Multi-material 3D bioprinting of porous constructs for cartilage regeneration. Mater Sci Eng C Mater Biol Appl. 2020;109:110578.
  178. Antich C, de Vicente J, Jimenez G, Chocarro C, Carrillo E, Montanez E, et al. Bio-inspired hydrogel composed of hyaluronic acid and alginate as a potential bioink for 3D bioprinting of articular cartilage engineering constructs. Acta Biomater. 2020;106:114-23.
  179. Zhao Z, Fan C, Chen F, Sun Y, Xia Y, Ji A, et al. Progress in Articular Cartilage Tissue Engineering: A Review on Therapeutic Cells and Macromolecular Scaffolds. Macromol Biosci. 2020;20(2):e1900278.
  180. Semba J, Mieloch A, Rybka J. Introduction to the state-of-the-art 3D bioprinting methods, design, and applications in orthopedics. Bioprinting. 2019;18:e00070.
The Archives of Bone and Joint Surgery
Volume 10, Issue 3
March 2022
Pages 229-244

  • Receive Date 18 February 2021
  • Revise Date 15 December 2021
  • Accept Date 19 January 2022