Hidrogeles de polimerización in situ para la regeneración de cartílago articular
Barra lateral del artículo
Publicado:
ago 5, 2019
Palabras clave:
Lesiones condrales focales, artrosis, hidrogeles, bioimpresión, regeneración, células madre. Focal chondral lesions, osteoarthritis, hydrogels, bioprinting, regeneration, stem cells.
Contenido principal del artículo
Resumen
Una significativa cantidad de adultos jóvenes activos sufre lesiones condrales focales. Estas lesiones, si no se tratan, pueden progresar hacia la artrosis, que es una de las principales enfermedades musculoesqueléticas debilitantes y de gran carga económica que afectan a toda sociedad. Pese a los tratamientos quirúrgicos disponibles para la reparación de defectos condrales focales sintomáticos que mejoran la calidad de vida a mediano plazo, hay un mayor riesgo de progresión hacia la artrosis prematura. Los tratamientos biológicos (células madre, bioingeniería tisular) han avanzado a grandes pasos en los últimos años. La bioingeniería es un área que ha progresado en la regeneración de cartílago articular y que potencialmente podría progresar en el terreno de tratamientos articulares, promoviendo la regeneración y evitando la degeneración. Las células madre y los hidrogeles pueden proveer un tejido símil biológico de comportamiento dinámico-funcional equivalente que induce la regeneración tisular al ser degradado y reemplazado gradualmente. El abordaje consiste en colocar un hidrogel precursor o un biomaterial tridimensional impreso dentro del defecto condral por ocupar para inducir la regeneración. Esta revisión se focaliza en el uso actual y futuro de hidrogeles y bioimpresión tridimensional para la regeneración de cartílago articular en el tratamiento de lesiones condrales focales y proporciona datos preliminares de dos estudios piloto en animales.
Abstract
A significant number of young active adults are affected by focal chondral lesions. These lesions, if left untreated, will progress to osteoarthritis (OA). OA is one of the main debilitating musculoskeletal diseases and leads to a high economic and social burden. Despite surgical cartilage repair for focal chondral lesions, which improve patient-reported outcomes at short- and mid-term, there is a risk of early OA progression. Biological treatments (i.e., stem-cell therapy, bioengineering) have made great progress in the last years. Tissue engineering is an evolving field for articular cartilage repair which could potentially be used for the treatment of focal chondral lesions, promoting regeneration and preventing joint surface degeneration. Stem cells and hydrogels may provide a functional, dynamic and biologically equivalent tissue that promotes tissue regeneration while being gradually degraded and replaced. The standard approach to tissue engineering consists in delivering cells within a hydrogel or a three-dimensional printed biomaterial scaffold into the chondral lesion to induce regeneration. This review focuses on the current and future use of hydrogels and tissue scaffold bioprinting for the treatment of focal chondral lesions, and provides preliminary data from two pilot animal studies.
Abstract
A significant number of young active adults are affected by focal chondral lesions. These lesions, if left untreated, will progress to osteoarthritis (OA). OA is one of the main debilitating musculoskeletal diseases and leads to a high economic and social burden. Despite surgical cartilage repair for focal chondral lesions, which improve patient-reported outcomes at short- and mid-term, there is a risk of early OA progression. Biological treatments (i.e., stem-cell therapy, bioengineering) have made great progress in the last years. Tissue engineering is an evolving field for articular cartilage repair which could potentially be used for the treatment of focal chondral lesions, promoting regeneration and preventing joint surface degeneration. Stem cells and hydrogels may provide a functional, dynamic and biologically equivalent tissue that promotes tissue regeneration while being gradually degraded and replaced. The standard approach to tissue engineering consists in delivering cells within a hydrogel or a three-dimensional printed biomaterial scaffold into the chondral lesion to induce regeneration. This review focuses on the current and future use of hydrogels and tissue scaffold bioprinting for the treatment of focal chondral lesions, and provides preliminary data from two pilot animal studies.
Descargas
La descarga de datos todavía no está disponible.
Métricas
Cargando métricas ...
Detalles del artículo
Cómo citar
Rodríguez-Fontán, F., & Pascual-Garrido, C. (2019). Hidrogeles de polimerización in situ para la regeneración de cartílago articular. Revista De La Asociación Argentina De Ortopedia Y Traumatología, 84(3), 296-308. https://doi.org/10.15417/issn.1852-7434.2019.84.3.956
Número
Sección
Artículo Especial
Derechos de autor 2019 Revista de la Asociación Argentina de Ortopedia y Traumatología
La aceptación del manuscrito por parte de la revista implica la no presentación simultánea a otras revistas u órganos editoriales. La RAAOT se encuentra bajo la licencia Creative Commons 4.0. Atribución-NoComercial-CompartirIgual (http://creativecommons.org/licenses/by-nc-sa/4.0/deed.es). Se puede compartir, copiar, distribuir, alterar, transformar, generar una obra derivada, ejecutar y comunicar públicamente la obra, siempre que: a) se cite la autoría y la fuente original de su publicación (revista, editorial y URL de la obra); b) no se usen para fines comerciales; c) se mantengan los mismos términos de la licencia.
En caso de que el manuscrito sea aprobado para su próxima publicación, los autores conservan los derechos de autor y cederán a la revista los derechos de la publicación, edición, reproducción, distribución, exhibición y comunicación a nivel nacional e internacional en las diferentes bases de datos, repositorios y portales.
Se deja constancia que el referido artículo es inédito y que no está en espera de impresión en alguna otra publicación nacional o extranjera.
Por la presente, acepta/n las modificaciones que sean necesarias, sugeridas en la revisión por los pares (referato), para adaptar el trabajo al estilo y modalidad de publicación de la Revista.
Citas
1. Loeser R. Integrins and chondrocyte-matrix interactions in articular cartilage.Matrix Biol 2014;39:11-6. https://doi.org/10.1016/j.matbio.2014.08.007
2. Hunziker EB. Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects.Osteoarthritis Cartilage 2002;10(6):432-63. https://doi.org/10.1053/joca.2002.0801
3. Vijayan S, Bentley G, Briggs T, Skinner J, Carrington R, Pollock R, et al. Cartilage repair: A review of Stanmore experience in the treatment of osteochondral defects in the knee with various surgical techniques. Indian J Orthop 2010;44(3):238-45. https://doi.org/10.4103/0019-5413.65136
4. Flanigan DC, Harris JD, Trinh TQ, Siston RA, Brophy RH. Prevalence of chondral defects in athletes' knees: a systematic review. Med Sci Sports Exerc 2010;42(10):1795-801. https://doi.org/10.1249/MSS.0b013e3181d9eea0
5. Vigdorchik J, Nepple J, Eftekhary N, Leunig M, Clohisy J.What is the association of elite sporting activities with the development of hip osteoarthritis? Am J Sports Med 2017;45(4):961-4. https://doi.org/10.1177/0363546516656359
6. Cole BJ, Pascual-Garrido C, Grumet RC. Surgical management of articular cartilage defects in the knee. J Bone Joint Surg Am 2009;91(7):1778-90. PMID: 19571102
7. Heijink A, Gomoll AH, Madry H, Drobnic M, Filardo G, Espregueira-Mendes J, et al. Biomechanical considerations in the pathogenesis of osteoarthritis of the knee. Knee Surg Sports Traumatol Arthrosc 2012;20(3):423-35. https://doi.org/10.1007/s00167-011-1818-0
8. Loeser RF, Goldring SR, Scanzello CR, Goldring MB. Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum 2012;64(6):1697-707. https://doi.org/10.1002/art.34453
9. Driban J, Hootman J, Sitler M, Harris K, Cattano N. Is participation in certain sports associated with knee osteoarthritis? A systematic review. J Athl Train 2017;52(6):497-506. https://doi.org/10.4085/1062-6050-50.2.08
10. Bedi A, Feeley BT, Williams RJ 3rd. Management of articular cartilage defects of the knee. J Bone Joint Surg Am 2010;92(4):994-1009. https://doi.org/10.2106/JBJS.I.00895
11. Park YB, Ha CW, Lee CH, Park YG. Restoration of a large osteochondral defect of the knee using a composite of umbilical cord blood-derived mesenchymal stem cells and hyaluronic acid hydrogel: a case report with a 5-year follow-up. BMC Musculoskelet Disord 2017;18(1):59. https://doi.org/10.1186/s12891-017-1422-7
12. Brittberg M, Recker D, Ilgenfritz J, Saris DBF. Matrix-applied characterized autologous cultured chondrocytes versus microfracture: five-year follow-up of a prospective randomized trial. Am J Sports Med 2018;46(6):1343-51. https://doi.org/10.1177/0363546518756976
13. Bornes TD, Adesida AB, Jomha NM. Mesenchymal stem cells in the treatment of traumatic articular cartilage defects: a comprehensive review. Arthritis Res Ther 2014;16(5):432. https://doi.org/10.1186/s13075-014-0432-1
14. Nicodemus GD, Bryant SJ. Cell encapsulation in biodegradable hydrogels for tissue engineering applications. Tissue Eng Part B Rev 2008;14(2):149-65. https://doi.org/10.1089/ten.teb.2007.0332
15. Vilela CA, Correia C, Oliveira JM, Sousa RA, Espregueira-Mendes J, Reis RL. Cartilage repair using hydrogels: a critical review of in vivo experimental designs. ACS Biomater Sci Eng 2015;1(9):726-39. https://doi.org/10.1021/acsbiomaterials.5b00245
16. Grande DA, Singh IJ, Pugh J. Healing of experimentally produced lesions in articular cartilage following chondrocyte transplantation. Anat Rec 1987;218(2):142-8. https://doi.org/10.1002/ar.1092180208
17. Grande DA, Pitman MI, Peterson L, Menche D, Klein M. The repair of experimentally produced defects in rabbit articular cartilage by autologous chondrocyte transplantation. J Orthop Res 1989;7(2):208-18. https://doi.org/10.1002/jor.1100070208
18. Peterson L, Vasiliadis HS, Brittberg M, Lindahl A. Autologous chondrocyte implantation: a long-term follow-up. Am J Sports Med 2010;38(6):1117-24. https://doi.org/10.1177/0363546509357915
19. Brittberg M. 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 2010;38(6):1259-71. https://doi.org/10.1177/0363546509346395
20. Jacobi M, Villa V, Magnussen RA, Neyret P. MACI - a new era? Sports Med Arthrosc Rehabil Ther Technol 2011;3(1):10. https://doi.org/10.1186/1758-2555-3-10
21. Makris EA, Gomoll AH, Malizos KN, Hu JC, Athanasiou KA. Repair and tissue engineering techniques for articular cartilage. Nat Rev Rheumatol 2015;11(1):21-34. https://doi.org/10.1038/nrrheum.2014.157
22. Gille J, Behrens P, Schulz AP, Oheim R, Kienast B. Matrix-associated autologous chondrocyte implantation: a clinical follow-up at 15 years.Cartilage 2016;7(4):309-15. https://doi.org/10.1177/1947603516638901
23. Ebert JR, Fallon M, Wood DJ, Janes GC. A prospective clinical and radiological evaluation at 5 years after arthroscopic matrix-induced autologous chondrocyte implantation. Am J Sports Med 2017;45(1):59-69. https://doi.org/10.1177/0363546516663493
24. Pascual-Garrido C, Slabaugh MA, L'Heureux DR, Friel NA, Cole BJ. Recommendations and treatment outcomes for patellofemoral articular cartilage defects with autologous chondrocyte implantation: prospective evaluation at average 4-year follow-up. Am J Sports Med 2009;37(Suppl 1):33s-41s. https://doi.org/10.1177/0363546509349605
25. Rodriguez Fontan F, Piuzzi N, Chahla J, Payne K, LaPrade R, Muschler G, et al. Stem and progenitor cells for cartilage repair: source, safety, evidence and efficacy.Operative Techniques in Sports Medicine 2017;25(1):25-33. https://doi.org/10.1053/j.otsm.2016.12.005
26. Nuttelman CR, Tripodi MC, Anseth KS. Synthetic hydrogel niches that promote hMSC viability. Matrix Biol 2005;24(3):208-18. https://doi.org/10.1016/j.matbio.2005.03.004
27. Zhu M, Feng Q, Sun Y, Li G, Bian L. Effect of cartilaginous matrix
components on the chondrogenesis and hypertrophy of mesenchymal stem cells in hyaluronic acid hydrogels. J Biomed Mater Res B Appl Biomater 2017;105(8):2292-300. https://doi.org/10.1002/jbm.b.33760
28. Masuoka K, Asazuma T, Hattori H, Yoshihara Y, Sato M, Matsumura K, et al. Tissue engineering of articular cartilage with autologous cultured adipose tissue-derived stromal cells using atelocollagen honeycomb-shaped scaffold with a membrane sealing in rabbits. J Biomed Mater Res B Appl Biomater 2006;79(1):25-34. https://doi.org/10.1002/jbm.b.30507
29. Dragoo JL, Carlson G, McCormick F, Khan-Farooqi H, Zhu M, Zuk PA, et al. Healing full-thickness cartilage defects using adipose-derived stem cells. Tissue Eng 2007;13(7):1615-21. https://doi.org/10.1089/ten.2006.0249
30. Park YB, Song M, Lee CH, Kim JA, Ha CW. Cartilage repair by human umbilical cord blood-derived mesenchymal stem cells with different hydrogels in a rat model. J Orthop Res 2015;33(11):1580-6. https://doi.org/10.1002/jor.22950
31. de Girolamo L, Niada S, Arrigoni E, Di Giancamillo A, Domeneghini C, Dadsetan M, et al. Repair of osteochondral defects in the minipig model by OPF hydrogel loaded with adipose-derived mesenchymal stem cells. Regen Med 2015;10(2):135-51. https://doi.org/10.2217/rme.14.77
32. Muschler GF, Nitto H, Boehm CA, Easley KA. Age- and gender-related changes in the cellularity of human bone marrow and the prevalence of osteoblastic progenitors. J Orthop Res 2001;19(1):117-25. https://doi.org/10.1016/S0736-0266(00)00010-3
33. Payne KA, Didiano DM, Chu CR. Donor sex and age influence the chondrogenic potential of human femoral bone marrow stem cells. Osteoarthritis Cartilage 2010;18(5):705-13. https://doi.org/10.1016/j.joca.2010.01.011
34. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007;131(5):861-72. https://doi.org/10.1016/j.cell.2007.11.019
35. Lietman SA. Induced pluripotent stem cells in cartilage repair. World J Orthop 2016;7(3):149-55. https://doi.org/10.5312/wjo.v7.i3.149. eCollection 2016 Mar 18
36. Liu J, Verma PJ. Synthetic mRNA reprogramming of human fibroblast cells. Methods Mol Biol 2015;1330:17-28. https://doi.org/10.1007/978-1-4939-2848-4_2
37. Choi HY, Lee TJ, Yang GM, Oh J, Won J, Han J, et al. Efficient mRNA delivery with graphene oxide-polyethylenimine for generation of footprint-free human induced pluripotent stem cells. J Control Release 2016;235:222-35. https://doi.org/10.1016/j.jconrel.2016.06.007
38. Uto S, Nishizawa S, Takasawa Y, Asawa Y, Fujihara Y, Takato T, et al. Bone and cartilage repair by transplantation of induced pluripotent stem cells in murine joint defect model. Biomed Res 2013;34(6):281-8. https://doi.org/10.2220/biomedres.34.281
39. Ko JY, Kim KI, Park S, Im GI. In vitro chondrogenesis and in vivo repair of osteochondral defect with human induced pluripotent stem cells. Biomaterials 2014;35(11):3571-81. https://doi.org/10.1016/j.biomaterials.2014.01.009
40. Kuroda T, Yasuda S, Kusakawa S, Hirata N, Kanda Y, Suzuki K, et al. Highly sensitive in vitro methods for detection of residual undifferentiated cells in retinal pigment epithelial cells derived from human iPS cells. PLoS One 2012;7(5):e37342. https://doi.org/10.1371/journal.pone.0037342
41. Itskovitz-Eldor J, Schuldiner M, Karsenti D, Eden A, Yanuka O, Amit M, et al. Differentiation of human embryonic stem cells into embryoid bodies compromising the three embryonic germ layers. Mol Med 2000;6(2):88-95. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1949933/
42. Cheng A, Kapacee Z, Peng J, Lu S, Lucas RJ, Hardingham TE, et al. Cartilage repair using human embryonic stem cell-derived chondroprogenitors. Stem Cells Transl Med 2014;3(11):1287-94. https://doi.org/10.5966/sctm.2014-0101
43. Elisseeff J, Puleo C, Yang F, Sharma B. Advances in skeletal tissue engineering with hydrogels.Orthod Craniofac Res 2005;8(3):150-61. https://doi.org/10.1111/j.1601-6343.2005.00335.x
44. Jukes JM, Moroni L, van Blitterswijk CA, de Boer J. Critical steps toward a tissue-engineered cartilage implant using embryonic stem cells. Tissue Eng Part A 2008;14(1):135-47. https://doi.org/10.1089/ten.a.2006.0397
45. Toh WS, Cao T. Derivation of chondrogenic cells from human embryonic stem cells for cartilage tissue engineering. Methods Mol Biol 2014. https://doi.org/10.1007/7651_2014_89
46. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, et al. Embryonic stem cell lines derived from human blastocysts. Science 1998;282(5391):1145-7. https://doi.org/10.1126/science.282.5391.1145
47. Bedouet L, Pascale F, Moine L, Wassef M, Ghegediban SH, Nguyen VN, et al. Intra-articular fate of degradable poly(ethyleneglycol)-hydrogel microspheres as carriers for sustained drug delivery. Int J Pharm 2013;456(2):536-44. https://doi.org/10.1016/j.ijpharm.2013.08.016
48. Griffith LG, Naughton G.Tissue engineering--current challenges and expanding opportunities. Science 2002;295(5557):1009-14. https://doi.org/10.1126/science.1069210
49. Castagnini F, Pellegrini C, Perazzo L,Vannini F, Buda R. Joint sparing treatments in early ankle osteoarthritis: current procedures and future perspectives. J Exp Orthop 2016;3(1):3. https://doi.org/10.1186/s40634-016-0038-4
50. Chen C, Bang S, Cho Y, Lee S, Lee I, Zhang S, et al. Research trends in biomimetic medical materials for tissue engineering: 3D bioprinting, surface modification, nano/micro-technology and clinical aspects in tissue engineering of cartilage and bone. Biomater Res 2016;20:10. https://doi.org/10.1186/s40824-016-0057-3. eCollection 2016
51. Li F, Su Y, Wang J, Wu G, Wang C. Influence of dynamic load on friction behavior of human articular cartilage, stainless steel and polyvinyl alcohol hydrogel as artificial cartilage. J Mater Sci Mater Med 2010;21(1):147-54. https://doi.org/10.1007/s10856-009-3863-5
52.Villanueva I, Hauschulz DS, Mejic D, Bryant SJ. Static and dynamic compressive strains influence nitric oxide production and chondrocyte bioactivity when encapsulated in PEG hydrogels of different crosslinking densities. Osteoarthritis Cartilage 2008;16(8):909-18. https://doi.org/10.1016/j.joca.2007.12.003
53. Elisseeff J, Anseth K, Sims D, McIntosh W, Randolph M, Yaremchuk M, et al. Transdermal photopolymerization of poly(ethylene oxide)-based injectable hydrogels for tissue-engineered cartilage. Plast Reconstr Surg 1999;104(4):1014-22. PMID: 10654741
54. Bryant SJ, Anseth KS.Hydrogel properties influence ECM production by chondrocytes photoencapsulated in poly(ethylene glycol) hydrogels. J Biomed Mater Res 2002;59(1):63-72. https://doi.org/10.1002/jbm.1217
55. Martens PJ, Bryant SJ, Anseth KS.Tailoring the degradation of hydrogels formed from multivinyl poly(ethylene glycol) and poly(vinyl alcohol) macromers for cartilage tissue engineering. Biomacromolecules 2003;4(2):283-92. https://doi.org/10.1021/bm025666v
56. Sharma B, Williams CG, Khan M, Manson P, Elisseeff JH. In vivo chondrogenesis of mesenchymal stem cells in a photopolymerized hydrogel. Plast Reconstr Surg 2007;119(1):112-20. https://doi.org/10.1097/01.prs.0000236896.22479.52
57. Sontjens SHM, Nettles DL, Carnahan MA, Setton LA, Grinstaff MW. Biodendrimer-based hydrogel scaffolds for cartilage tissue repair. Biomacromolecules 2006;7:310. https://doi.org/10.1021/bm050663e
58. Tatara AM, Mikos AG.Tissue engineering in Orthopaedics. J Bone Joint Surg Am 2016;98(13):1132-9. https://doi.org/10.2106/JBJS.16.00299
59. Vo TN, Tabata Y, Mikos AG. Effects of cellular parameters on the in vitro osteogenic potential of dual-gelling mesenchymal stem cell-laden hydrogels. J Biomater Sci Polym Ed 2016;27(12):1277-90. https://doi.org/10.1080/09205063.2016.1195157
60. Bryant SJ, Arthur JA, Anseth KS. Incorporation of tissue-specific molecules alters chondrocyte metabolism and gene expression in photocrosslinked hydrogels. Acta Biomater 2005;1:243. https://doi.org/10.1016/j.actbio.2004.11.003
61. Varghese S, Hwang NS, Canver AC, Theprungsirikul P, Lin DW, Elisseeff J. Chondroitin sulfate based niches for chondrogenic differentiation of mesenchymal stem cells. Matrix Biol 2008;27(1):12-21. https://doi.org/10.1016/j.matbio.2007.07.002
62. Smeriglio P, Lai JH, Yang F, Bhutani N. 3D hydrogel scaffolds for articular chondrocyte culture and cartilage generation. J Vis Exp 2015;(104). https://doi.org/10.3791/53085
63. Barros D, Amaral IF, Pego AP. Biomimetic synthetic self-assembled hydrogels for cell transplantation. Curr Top Med Chem 2015;15(13):1209-26. https://doi.org/10.2174/1568026615666150330111057
64. Han F, Yang X, Zhao J, Zhao Y, Yuan X. Photocrosslinked layered gelatin-chitosan hydrogel with graded compositions for osteochondral defect repair. J Mater Sci Mater Med 2015;26(4):160. https://doi.org/10.1007/s10856-015-5489-0
65. Spiller KL, Maher SA, Lowman AM. Hydrogels for the repair of articular cartilage defects.Tissue Eng Part B Rev 2011;17(4):281-99. https://doi.org/10.1089/ten.TEB.2011.0077
66. Beck EC, Barragan M, Tadros MH, Gehrke SH, Detamore MS. Approaching the compressive modulus of articular cartilage with a decellularized cartilage-based hydrogel. Acta Biomater 2016;38:94-105. https://doi.org/10.1016/j.actbio.2016.04.019
67. Nicodemus GD, Skaalure SC, Bryant SJ. Gel structure has an impact on pericellular and extracellular matrix deposition, which subsequently alters metabolic activities in chondrocyte-laden PEG hydrogels. Acta Biomater 2011;7(2):492-504. https://doi.org/10.1016/j.actbio.2010.08.021
68. Chung C, Beecham M, Mauck RL, Burdick JA.The influence of degradation characteristics of hyaluronic acid hydrogels on in vitro neocartilage formation by mesenchymal stem cells. Biomaterials 2009;30(26):4287-96. https://doi.org/10.1016/j.biomaterials.2009.04.040
69. Bryant SJ, Bender RJ, Durand KL, Anseth KS. Encapsulating chondrocytes in degrading PEG hydrogels with high modulus: engineering gel structural changes to facilitate cartilaginous tissue production. Biotechnol Bioeng 2004;86(7):747-55. https://doi.org/10.1002/bit.20160
70. Roberts JJ, Nicodemus GD, Greenwald EC, Bryant SJ. Degradation improves tissue formation in (un)loaded chondrocyte-laden hydrogels. Clin Orthop Relat Res 2011;469(10):2725-34. https://doi.org/10.1007/s11999-011-1823-0
71. Bahney CS, Hsu CW, Yoo JU, West JL, Johnstone B. A bioresponsive hydrogel tuned to chondrogenesis of human mesenchymal stem cells. FASEB J 2011;25(5):1486-96. https://doi.org/10.1096/fj.10-165514
72. Skaalure SC, Chu S, Bryant SJ. An enzyme-sensitive PEG hydrogel based on aggrecan catabolism for cartilage tissue engineering. Adv Healthc Mater 2015;4(3):420-31. https://doi.org/10.1002/adhm.201400277
73. Liebesny PH, Byun S, Hung HH, Pancoast JR, Mroszczyk KA, Young WT, et al. Growth factor-mediated migration of bone marrow progenitor cells for accelerated scaffold recruitment. Tissue Eng Part A 2016;22(13-14):917-27. https://doi.org/10.1089/ten.TEA.2015.0524
74. Sharma B, Fermanian S, Gibson M, Unterman S, Herzka D, Cascio B, et al. Human cartilage repair with a photoreactive adhesive-hydrogel composite. Sci Transl Med 2013;5(167):167ra6. https://doi.org/10.1126/scitranslmed.3004838
75. Aisenbrey EA, Bryant SJ. Mechanical loading inhibits hypertrophy in chondrogenically differentiating hMSCs within a biomimetic hydrogel. J Mater Chem B Mater Biol Med 2016;4(20):3562-74. https://doi.org/10.1039/c6tb00006a
76. Urban JP, Bayliss MT. Regulation of proteoglycan synthesis rate in cartilage in vitro: influence of extracellular ionic composition. Biochim Biophys Acta 1989;992(1):59-65. https://doi.org/10.1016/0304-4165(89)90050-0
77. Villanueva I, Gladem SK,Kessler J, Bryant SJ. Dynamic loading stimulates chondrocyte biosynthesis when encapsulated in charged hydrogels prepared from poly(ethylene glycol) and chondroitin sulfate. Matrix Biol 2010;29(1):51-62. https://doi.org/10.1016/j.matbio.2009.08.004
78. Farnsworth NL, Mead BE, Antunez LR, Palmer AE, Bryant SJ. Ionic osmolytes and intracellular calcium regulate tissue production in chondrocytes cultured in a 3D charged hydrogel. Matrix Biol 2014;40:17-26. https://doi.org/10.1016/j.matbio.2014.08.002
79. Villanueva I, Weigel CA, Bryant SJ. Cell-matrix interactions and dynamic mechanical loading influence chondrocyte gene expression and bioactivity in PEG-RGD hydrogels. Acta Biomater 2009;5(8):2832-46. https://doi.org/10.1016/j.actbio.2009.05.039
80. Salinas CN, Cole BB, Kasko AM, Anseth KS. Chondrogenic differentiation potential of human mesenchymal stem cells photoencapsulated within poly(ethylene glycol)-arginine-glycine-aspartic acid-serine thiol-methacrylate mixed-mode networks. Tissue Eng 2007;13(5):1025-34. https://doi.org/10.1089/ten.2006.0126
81. Liu SQ, Tian Q, Wang L, Hedrick JL, Hui JH, Yang YY, et al. Injectable biodegradable poly(ethylene glycol)/RGD peptide hybrid hydrogels for in vitro chondrogenesis of human mesenchymal stem cells. Macromol Rapid Commun 2010;31(13):1148-54. https://doi.org/10.1002/marc.200900818
82. Hoyle CE, Bowman CN. Thiol-ene click chemistry. Angew Chem Int Ed Engl 2010;49(9):1540-73. https://doi.org/10.1002/anie.200903924
83. Steinmetz NJ, Aisenbrey EA, Westbrook KK, Qi HJ, Bryant SJ. Mechanical loading regulates human MSC differentiation in a multi-layer hydrogel for osteochondral tissue engineering. Acta Biomater 2015;21:142-53. https://doi.org/10.1016/j.actbio.2015.04.015
84. Hoemann C, Kandel R, Roberts S, Saris DB, Creemers L, Mainil-Varlet P, et al. International Cartilage Repair Society (ICRS) Recommended Guidelines for Histological Endpoints for Cartilage Repair Studies in Animal Models and Clinical Trials. Cartilage 2011;2(2):153-72. https://doi.org/10.1177/1947603510397535
85. Pascual-Garrido C, Aisenbrey EA, Rodriguez-Fontan F, Payne KA, Bryant SJ, Goodrich LR. Photopolymerizable injectable cartilage mimetic hydrogel for the treatment of focal chondral lesions: aproof of concept study in a rabbit animal model. Am J Sports Med 2019;47(1):212. https://doi.org/10.1177/0363546518808012
86. Orth P, Madry H. Complex and elementary histological scoring systems for articular cartilage repair. Histol Histopathol 2015;30(8):911-9. https://doi.org/10.14670/HH-11-620
87. He Y, Yang F, Zhao H, Gao Q, Xia B, Fu J. Research on the printability of hydrogels in 3D bioprinting. Sci Rep 2016;6:29977. https://doi.org/10.1038/srep29977
88. Guo X, Park H, Young S, Kretlow JD, van den Beucken JJ, Baggett LS, et al. Repair of osteochondral defects with biodegradable hydrogel composites encapsulating marrow mesenchymal stem cells in a rabbit model. Acta Biomater 2010;6(1):39-47. https://doi.org/10.1016/j.actbio.2009.07.041
89. Lim CT, Ren X, Afizah MH, Tarigan-Panjaitan S, Yang Z, Wu Y, et al. Repair of osteochondral defects with rehydrated freeze-dried oligo[poly(ethylene glycol) fumarate] hydrogels seeded with bone marrow mesenchymal stem cells in a porcine model. Tissue Eng Part A 2013;19(15-16):1852-61. https://doi.org/10.1089/ten.TEA.2012.0621
90. Lam J, Lu S, Lee EJ, Trachtenberg JE, Meretoja VV, Dahlin RL, et al. Osteochondral defect repair using bilayered hydrogels encapsulating both chondrogenically and osteogenically pre-differentiated mesenchymal stem cells in a rabbit model. Osteoarthritis Cartilage 2014;22(9):1291-300. https://doi.org/10.1016/j.joca.2014.06.035
91. Saxena V, Kim M, Keah NM, Neuwirth AL, Stoeckl BD, Bickard K, et al. Anatomic mesenchymal stem cell-based engineered cartilage constructs for biologic total joint replacement. Tissue Eng Part A 2016;22(3-4):386-95. https://doi.org/10.1089/ten.tea.2015.0384
92. Lespasio MJ, Piuzzi NS, Husni ME, Muschler GF, Guarino A, MA M. Knee osteoarthritis: A primer. Perm J 2017;21:16-183. https://doi.org/10.7812/TPP/16-183
93. Lespasio MJ, Sultan AA, Piuzzi NS, Khlopas A, Husni ME, Muschler GF, et al. Hip osteoarthritis: A primer. Perm J 2018;22:17-084. https://doi.org/10.7812/TPP/17-084
94. Iorio R, Robb WJ, Healy WL, Berry DJ, Hozack WJ, Kyle RF, et al. Orthopaedic surgeon workforce and volume assessment for total hip and knee replacement in the United States: preparing for an epidemic. J Bone Joint Surg Am 2008;90(7):1598-605. https://doi.org/10.2106/JBJS.H.00067
95. Moutos FT, Glass KA, Compton SA, Ross AK, Gersbach CA, Guilak F, et al. Anatomically shaped tissue-engineered cartilage with tunable and inducible anticytokine delivery for biological joint resurfacing. Proc Natl Acad Sci USA 2016;113(31):E4513-22. https://doi.org/10.1073/pnas.1601639113
96. Rowland CR, Colucci LA, Guilak F. Fabrication of anatomically-shaped cartilage constructs using decellularized cartilage-derived matrix scaffolds. Biomaterials 2016;91:57-72. https://doi.org/10.1016/j.biomaterials.2016.03.012
97. Rey-Rico A, Cucchiarini M, Madry H. Hydrogels for precision meniscus tissue engineering: a comprehensive review. Connect Tissue Res 2017;58(3-4):317-328. https://doi.org/10.1080/03008207.2016.1276576
98. Shaw N, Erickson C, Bryant SJ, Ferguson VL, Krebs MD, Hadley-Miller N, et al. Regenerative medicine approaches for the treatment of pediatric physeal injuries. Tissue Eng Part B Rev 2018;24(2):85-97. https://doi.org/10.1089/ten.TEB.2017.0274
99. Gibbs DM, Black CR, Dawson JI, Oreffo RO. A review of hydrogel use in fracture healing and bone regeneration. J Tissue Eng Regen Med 2016;10(3):187-98. https://doi.org/10.1002/term.1968
100. Pot MW, Gonzales VK, Buma P, IntHout J, van Kuppevelt TH, de Vries RBM, et al. Improved cartilage regeneration by implantation of acellular biomaterials after bone marrow stimulation: a systematic review and meta-analysis of animal studies. Peer J 2016;4:e2243. https://doi.org/10.7717/peerj.2243. eCollection 2016
101. Shive MS, Stanish WD, McCormack R, Forriol F, Mohtadi N, Pelet S, et al. BST-CarGel(R) treatment maintains cartilage repair superiority over microfracture at 5 years in a multicenter randomized controlled trial. Cartilage 2015;6(2):62-72. https://doi.org/10.1177/1947603514562064
2. Hunziker EB. Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects.Osteoarthritis Cartilage 2002;10(6):432-63. https://doi.org/10.1053/joca.2002.0801
3. Vijayan S, Bentley G, Briggs T, Skinner J, Carrington R, Pollock R, et al. Cartilage repair: A review of Stanmore experience in the treatment of osteochondral defects in the knee with various surgical techniques. Indian J Orthop 2010;44(3):238-45. https://doi.org/10.4103/0019-5413.65136
4. Flanigan DC, Harris JD, Trinh TQ, Siston RA, Brophy RH. Prevalence of chondral defects in athletes' knees: a systematic review. Med Sci Sports Exerc 2010;42(10):1795-801. https://doi.org/10.1249/MSS.0b013e3181d9eea0
5. Vigdorchik J, Nepple J, Eftekhary N, Leunig M, Clohisy J.What is the association of elite sporting activities with the development of hip osteoarthritis? Am J Sports Med 2017;45(4):961-4. https://doi.org/10.1177/0363546516656359
6. Cole BJ, Pascual-Garrido C, Grumet RC. Surgical management of articular cartilage defects in the knee. J Bone Joint Surg Am 2009;91(7):1778-90. PMID: 19571102
7. Heijink A, Gomoll AH, Madry H, Drobnic M, Filardo G, Espregueira-Mendes J, et al. Biomechanical considerations in the pathogenesis of osteoarthritis of the knee. Knee Surg Sports Traumatol Arthrosc 2012;20(3):423-35. https://doi.org/10.1007/s00167-011-1818-0
8. Loeser RF, Goldring SR, Scanzello CR, Goldring MB. Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum 2012;64(6):1697-707. https://doi.org/10.1002/art.34453
9. Driban J, Hootman J, Sitler M, Harris K, Cattano N. Is participation in certain sports associated with knee osteoarthritis? A systematic review. J Athl Train 2017;52(6):497-506. https://doi.org/10.4085/1062-6050-50.2.08
10. Bedi A, Feeley BT, Williams RJ 3rd. Management of articular cartilage defects of the knee. J Bone Joint Surg Am 2010;92(4):994-1009. https://doi.org/10.2106/JBJS.I.00895
11. Park YB, Ha CW, Lee CH, Park YG. Restoration of a large osteochondral defect of the knee using a composite of umbilical cord blood-derived mesenchymal stem cells and hyaluronic acid hydrogel: a case report with a 5-year follow-up. BMC Musculoskelet Disord 2017;18(1):59. https://doi.org/10.1186/s12891-017-1422-7
12. Brittberg M, Recker D, Ilgenfritz J, Saris DBF. Matrix-applied characterized autologous cultured chondrocytes versus microfracture: five-year follow-up of a prospective randomized trial. Am J Sports Med 2018;46(6):1343-51. https://doi.org/10.1177/0363546518756976
13. Bornes TD, Adesida AB, Jomha NM. Mesenchymal stem cells in the treatment of traumatic articular cartilage defects: a comprehensive review. Arthritis Res Ther 2014;16(5):432. https://doi.org/10.1186/s13075-014-0432-1
14. Nicodemus GD, Bryant SJ. Cell encapsulation in biodegradable hydrogels for tissue engineering applications. Tissue Eng Part B Rev 2008;14(2):149-65. https://doi.org/10.1089/ten.teb.2007.0332
15. Vilela CA, Correia C, Oliveira JM, Sousa RA, Espregueira-Mendes J, Reis RL. Cartilage repair using hydrogels: a critical review of in vivo experimental designs. ACS Biomater Sci Eng 2015;1(9):726-39. https://doi.org/10.1021/acsbiomaterials.5b00245
16. Grande DA, Singh IJ, Pugh J. Healing of experimentally produced lesions in articular cartilage following chondrocyte transplantation. Anat Rec 1987;218(2):142-8. https://doi.org/10.1002/ar.1092180208
17. Grande DA, Pitman MI, Peterson L, Menche D, Klein M. The repair of experimentally produced defects in rabbit articular cartilage by autologous chondrocyte transplantation. J Orthop Res 1989;7(2):208-18. https://doi.org/10.1002/jor.1100070208
18. Peterson L, Vasiliadis HS, Brittberg M, Lindahl A. Autologous chondrocyte implantation: a long-term follow-up. Am J Sports Med 2010;38(6):1117-24. https://doi.org/10.1177/0363546509357915
19. Brittberg M. 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 2010;38(6):1259-71. https://doi.org/10.1177/0363546509346395
20. Jacobi M, Villa V, Magnussen RA, Neyret P. MACI - a new era? Sports Med Arthrosc Rehabil Ther Technol 2011;3(1):10. https://doi.org/10.1186/1758-2555-3-10
21. Makris EA, Gomoll AH, Malizos KN, Hu JC, Athanasiou KA. Repair and tissue engineering techniques for articular cartilage. Nat Rev Rheumatol 2015;11(1):21-34. https://doi.org/10.1038/nrrheum.2014.157
22. Gille J, Behrens P, Schulz AP, Oheim R, Kienast B. Matrix-associated autologous chondrocyte implantation: a clinical follow-up at 15 years.Cartilage 2016;7(4):309-15. https://doi.org/10.1177/1947603516638901
23. Ebert JR, Fallon M, Wood DJ, Janes GC. A prospective clinical and radiological evaluation at 5 years after arthroscopic matrix-induced autologous chondrocyte implantation. Am J Sports Med 2017;45(1):59-69. https://doi.org/10.1177/0363546516663493
24. Pascual-Garrido C, Slabaugh MA, L'Heureux DR, Friel NA, Cole BJ. Recommendations and treatment outcomes for patellofemoral articular cartilage defects with autologous chondrocyte implantation: prospective evaluation at average 4-year follow-up. Am J Sports Med 2009;37(Suppl 1):33s-41s. https://doi.org/10.1177/0363546509349605
25. Rodriguez Fontan F, Piuzzi N, Chahla J, Payne K, LaPrade R, Muschler G, et al. Stem and progenitor cells for cartilage repair: source, safety, evidence and efficacy.Operative Techniques in Sports Medicine 2017;25(1):25-33. https://doi.org/10.1053/j.otsm.2016.12.005
26. Nuttelman CR, Tripodi MC, Anseth KS. Synthetic hydrogel niches that promote hMSC viability. Matrix Biol 2005;24(3):208-18. https://doi.org/10.1016/j.matbio.2005.03.004
27. Zhu M, Feng Q, Sun Y, Li G, Bian L. Effect of cartilaginous matrix
components on the chondrogenesis and hypertrophy of mesenchymal stem cells in hyaluronic acid hydrogels. J Biomed Mater Res B Appl Biomater 2017;105(8):2292-300. https://doi.org/10.1002/jbm.b.33760
28. Masuoka K, Asazuma T, Hattori H, Yoshihara Y, Sato M, Matsumura K, et al. Tissue engineering of articular cartilage with autologous cultured adipose tissue-derived stromal cells using atelocollagen honeycomb-shaped scaffold with a membrane sealing in rabbits. J Biomed Mater Res B Appl Biomater 2006;79(1):25-34. https://doi.org/10.1002/jbm.b.30507
29. Dragoo JL, Carlson G, McCormick F, Khan-Farooqi H, Zhu M, Zuk PA, et al. Healing full-thickness cartilage defects using adipose-derived stem cells. Tissue Eng 2007;13(7):1615-21. https://doi.org/10.1089/ten.2006.0249
30. Park YB, Song M, Lee CH, Kim JA, Ha CW. Cartilage repair by human umbilical cord blood-derived mesenchymal stem cells with different hydrogels in a rat model. J Orthop Res 2015;33(11):1580-6. https://doi.org/10.1002/jor.22950
31. de Girolamo L, Niada S, Arrigoni E, Di Giancamillo A, Domeneghini C, Dadsetan M, et al. Repair of osteochondral defects in the minipig model by OPF hydrogel loaded with adipose-derived mesenchymal stem cells. Regen Med 2015;10(2):135-51. https://doi.org/10.2217/rme.14.77
32. Muschler GF, Nitto H, Boehm CA, Easley KA. Age- and gender-related changes in the cellularity of human bone marrow and the prevalence of osteoblastic progenitors. J Orthop Res 2001;19(1):117-25. https://doi.org/10.1016/S0736-0266(00)00010-3
33. Payne KA, Didiano DM, Chu CR. Donor sex and age influence the chondrogenic potential of human femoral bone marrow stem cells. Osteoarthritis Cartilage 2010;18(5):705-13. https://doi.org/10.1016/j.joca.2010.01.011
34. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007;131(5):861-72. https://doi.org/10.1016/j.cell.2007.11.019
35. Lietman SA. Induced pluripotent stem cells in cartilage repair. World J Orthop 2016;7(3):149-55. https://doi.org/10.5312/wjo.v7.i3.149. eCollection 2016 Mar 18
36. Liu J, Verma PJ. Synthetic mRNA reprogramming of human fibroblast cells. Methods Mol Biol 2015;1330:17-28. https://doi.org/10.1007/978-1-4939-2848-4_2
37. Choi HY, Lee TJ, Yang GM, Oh J, Won J, Han J, et al. Efficient mRNA delivery with graphene oxide-polyethylenimine for generation of footprint-free human induced pluripotent stem cells. J Control Release 2016;235:222-35. https://doi.org/10.1016/j.jconrel.2016.06.007
38. Uto S, Nishizawa S, Takasawa Y, Asawa Y, Fujihara Y, Takato T, et al. Bone and cartilage repair by transplantation of induced pluripotent stem cells in murine joint defect model. Biomed Res 2013;34(6):281-8. https://doi.org/10.2220/biomedres.34.281
39. Ko JY, Kim KI, Park S, Im GI. In vitro chondrogenesis and in vivo repair of osteochondral defect with human induced pluripotent stem cells. Biomaterials 2014;35(11):3571-81. https://doi.org/10.1016/j.biomaterials.2014.01.009
40. Kuroda T, Yasuda S, Kusakawa S, Hirata N, Kanda Y, Suzuki K, et al. Highly sensitive in vitro methods for detection of residual undifferentiated cells in retinal pigment epithelial cells derived from human iPS cells. PLoS One 2012;7(5):e37342. https://doi.org/10.1371/journal.pone.0037342
41. Itskovitz-Eldor J, Schuldiner M, Karsenti D, Eden A, Yanuka O, Amit M, et al. Differentiation of human embryonic stem cells into embryoid bodies compromising the three embryonic germ layers. Mol Med 2000;6(2):88-95. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1949933/
42. Cheng A, Kapacee Z, Peng J, Lu S, Lucas RJ, Hardingham TE, et al. Cartilage repair using human embryonic stem cell-derived chondroprogenitors. Stem Cells Transl Med 2014;3(11):1287-94. https://doi.org/10.5966/sctm.2014-0101
43. Elisseeff J, Puleo C, Yang F, Sharma B. Advances in skeletal tissue engineering with hydrogels.Orthod Craniofac Res 2005;8(3):150-61. https://doi.org/10.1111/j.1601-6343.2005.00335.x
44. Jukes JM, Moroni L, van Blitterswijk CA, de Boer J. Critical steps toward a tissue-engineered cartilage implant using embryonic stem cells. Tissue Eng Part A 2008;14(1):135-47. https://doi.org/10.1089/ten.a.2006.0397
45. Toh WS, Cao T. Derivation of chondrogenic cells from human embryonic stem cells for cartilage tissue engineering. Methods Mol Biol 2014. https://doi.org/10.1007/7651_2014_89
46. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, et al. Embryonic stem cell lines derived from human blastocysts. Science 1998;282(5391):1145-7. https://doi.org/10.1126/science.282.5391.1145
47. Bedouet L, Pascale F, Moine L, Wassef M, Ghegediban SH, Nguyen VN, et al. Intra-articular fate of degradable poly(ethyleneglycol)-hydrogel microspheres as carriers for sustained drug delivery. Int J Pharm 2013;456(2):536-44. https://doi.org/10.1016/j.ijpharm.2013.08.016
48. Griffith LG, Naughton G.Tissue engineering--current challenges and expanding opportunities. Science 2002;295(5557):1009-14. https://doi.org/10.1126/science.1069210
49. Castagnini F, Pellegrini C, Perazzo L,Vannini F, Buda R. Joint sparing treatments in early ankle osteoarthritis: current procedures and future perspectives. J Exp Orthop 2016;3(1):3. https://doi.org/10.1186/s40634-016-0038-4
50. Chen C, Bang S, Cho Y, Lee S, Lee I, Zhang S, et al. Research trends in biomimetic medical materials for tissue engineering: 3D bioprinting, surface modification, nano/micro-technology and clinical aspects in tissue engineering of cartilage and bone. Biomater Res 2016;20:10. https://doi.org/10.1186/s40824-016-0057-3. eCollection 2016
51. Li F, Su Y, Wang J, Wu G, Wang C. Influence of dynamic load on friction behavior of human articular cartilage, stainless steel and polyvinyl alcohol hydrogel as artificial cartilage. J Mater Sci Mater Med 2010;21(1):147-54. https://doi.org/10.1007/s10856-009-3863-5
52.Villanueva I, Hauschulz DS, Mejic D, Bryant SJ. Static and dynamic compressive strains influence nitric oxide production and chondrocyte bioactivity when encapsulated in PEG hydrogels of different crosslinking densities. Osteoarthritis Cartilage 2008;16(8):909-18. https://doi.org/10.1016/j.joca.2007.12.003
53. Elisseeff J, Anseth K, Sims D, McIntosh W, Randolph M, Yaremchuk M, et al. Transdermal photopolymerization of poly(ethylene oxide)-based injectable hydrogels for tissue-engineered cartilage. Plast Reconstr Surg 1999;104(4):1014-22. PMID: 10654741
54. Bryant SJ, Anseth KS.Hydrogel properties influence ECM production by chondrocytes photoencapsulated in poly(ethylene glycol) hydrogels. J Biomed Mater Res 2002;59(1):63-72. https://doi.org/10.1002/jbm.1217
55. Martens PJ, Bryant SJ, Anseth KS.Tailoring the degradation of hydrogels formed from multivinyl poly(ethylene glycol) and poly(vinyl alcohol) macromers for cartilage tissue engineering. Biomacromolecules 2003;4(2):283-92. https://doi.org/10.1021/bm025666v
56. Sharma B, Williams CG, Khan M, Manson P, Elisseeff JH. In vivo chondrogenesis of mesenchymal stem cells in a photopolymerized hydrogel. Plast Reconstr Surg 2007;119(1):112-20. https://doi.org/10.1097/01.prs.0000236896.22479.52
57. Sontjens SHM, Nettles DL, Carnahan MA, Setton LA, Grinstaff MW. Biodendrimer-based hydrogel scaffolds for cartilage tissue repair. Biomacromolecules 2006;7:310. https://doi.org/10.1021/bm050663e
58. Tatara AM, Mikos AG.Tissue engineering in Orthopaedics. J Bone Joint Surg Am 2016;98(13):1132-9. https://doi.org/10.2106/JBJS.16.00299
59. Vo TN, Tabata Y, Mikos AG. Effects of cellular parameters on the in vitro osteogenic potential of dual-gelling mesenchymal stem cell-laden hydrogels. J Biomater Sci Polym Ed 2016;27(12):1277-90. https://doi.org/10.1080/09205063.2016.1195157
60. Bryant SJ, Arthur JA, Anseth KS. Incorporation of tissue-specific molecules alters chondrocyte metabolism and gene expression in photocrosslinked hydrogels. Acta Biomater 2005;1:243. https://doi.org/10.1016/j.actbio.2004.11.003
61. Varghese S, Hwang NS, Canver AC, Theprungsirikul P, Lin DW, Elisseeff J. Chondroitin sulfate based niches for chondrogenic differentiation of mesenchymal stem cells. Matrix Biol 2008;27(1):12-21. https://doi.org/10.1016/j.matbio.2007.07.002
62. Smeriglio P, Lai JH, Yang F, Bhutani N. 3D hydrogel scaffolds for articular chondrocyte culture and cartilage generation. J Vis Exp 2015;(104). https://doi.org/10.3791/53085
63. Barros D, Amaral IF, Pego AP. Biomimetic synthetic self-assembled hydrogels for cell transplantation. Curr Top Med Chem 2015;15(13):1209-26. https://doi.org/10.2174/1568026615666150330111057
64. Han F, Yang X, Zhao J, Zhao Y, Yuan X. Photocrosslinked layered gelatin-chitosan hydrogel with graded compositions for osteochondral defect repair. J Mater Sci Mater Med 2015;26(4):160. https://doi.org/10.1007/s10856-015-5489-0
65. Spiller KL, Maher SA, Lowman AM. Hydrogels for the repair of articular cartilage defects.Tissue Eng Part B Rev 2011;17(4):281-99. https://doi.org/10.1089/ten.TEB.2011.0077
66. Beck EC, Barragan M, Tadros MH, Gehrke SH, Detamore MS. Approaching the compressive modulus of articular cartilage with a decellularized cartilage-based hydrogel. Acta Biomater 2016;38:94-105. https://doi.org/10.1016/j.actbio.2016.04.019
67. Nicodemus GD, Skaalure SC, Bryant SJ. Gel structure has an impact on pericellular and extracellular matrix deposition, which subsequently alters metabolic activities in chondrocyte-laden PEG hydrogels. Acta Biomater 2011;7(2):492-504. https://doi.org/10.1016/j.actbio.2010.08.021
68. Chung C, Beecham M, Mauck RL, Burdick JA.The influence of degradation characteristics of hyaluronic acid hydrogels on in vitro neocartilage formation by mesenchymal stem cells. Biomaterials 2009;30(26):4287-96. https://doi.org/10.1016/j.biomaterials.2009.04.040
69. Bryant SJ, Bender RJ, Durand KL, Anseth KS. Encapsulating chondrocytes in degrading PEG hydrogels with high modulus: engineering gel structural changes to facilitate cartilaginous tissue production. Biotechnol Bioeng 2004;86(7):747-55. https://doi.org/10.1002/bit.20160
70. Roberts JJ, Nicodemus GD, Greenwald EC, Bryant SJ. Degradation improves tissue formation in (un)loaded chondrocyte-laden hydrogels. Clin Orthop Relat Res 2011;469(10):2725-34. https://doi.org/10.1007/s11999-011-1823-0
71. Bahney CS, Hsu CW, Yoo JU, West JL, Johnstone B. A bioresponsive hydrogel tuned to chondrogenesis of human mesenchymal stem cells. FASEB J 2011;25(5):1486-96. https://doi.org/10.1096/fj.10-165514
72. Skaalure SC, Chu S, Bryant SJ. An enzyme-sensitive PEG hydrogel based on aggrecan catabolism for cartilage tissue engineering. Adv Healthc Mater 2015;4(3):420-31. https://doi.org/10.1002/adhm.201400277
73. Liebesny PH, Byun S, Hung HH, Pancoast JR, Mroszczyk KA, Young WT, et al. Growth factor-mediated migration of bone marrow progenitor cells for accelerated scaffold recruitment. Tissue Eng Part A 2016;22(13-14):917-27. https://doi.org/10.1089/ten.TEA.2015.0524
74. Sharma B, Fermanian S, Gibson M, Unterman S, Herzka D, Cascio B, et al. Human cartilage repair with a photoreactive adhesive-hydrogel composite. Sci Transl Med 2013;5(167):167ra6. https://doi.org/10.1126/scitranslmed.3004838
75. Aisenbrey EA, Bryant SJ. Mechanical loading inhibits hypertrophy in chondrogenically differentiating hMSCs within a biomimetic hydrogel. J Mater Chem B Mater Biol Med 2016;4(20):3562-74. https://doi.org/10.1039/c6tb00006a
76. Urban JP, Bayliss MT. Regulation of proteoglycan synthesis rate in cartilage in vitro: influence of extracellular ionic composition. Biochim Biophys Acta 1989;992(1):59-65. https://doi.org/10.1016/0304-4165(89)90050-0
77. Villanueva I, Gladem SK,Kessler J, Bryant SJ. Dynamic loading stimulates chondrocyte biosynthesis when encapsulated in charged hydrogels prepared from poly(ethylene glycol) and chondroitin sulfate. Matrix Biol 2010;29(1):51-62. https://doi.org/10.1016/j.matbio.2009.08.004
78. Farnsworth NL, Mead BE, Antunez LR, Palmer AE, Bryant SJ. Ionic osmolytes and intracellular calcium regulate tissue production in chondrocytes cultured in a 3D charged hydrogel. Matrix Biol 2014;40:17-26. https://doi.org/10.1016/j.matbio.2014.08.002
79. Villanueva I, Weigel CA, Bryant SJ. Cell-matrix interactions and dynamic mechanical loading influence chondrocyte gene expression and bioactivity in PEG-RGD hydrogels. Acta Biomater 2009;5(8):2832-46. https://doi.org/10.1016/j.actbio.2009.05.039
80. Salinas CN, Cole BB, Kasko AM, Anseth KS. Chondrogenic differentiation potential of human mesenchymal stem cells photoencapsulated within poly(ethylene glycol)-arginine-glycine-aspartic acid-serine thiol-methacrylate mixed-mode networks. Tissue Eng 2007;13(5):1025-34. https://doi.org/10.1089/ten.2006.0126
81. Liu SQ, Tian Q, Wang L, Hedrick JL, Hui JH, Yang YY, et al. Injectable biodegradable poly(ethylene glycol)/RGD peptide hybrid hydrogels for in vitro chondrogenesis of human mesenchymal stem cells. Macromol Rapid Commun 2010;31(13):1148-54. https://doi.org/10.1002/marc.200900818
82. Hoyle CE, Bowman CN. Thiol-ene click chemistry. Angew Chem Int Ed Engl 2010;49(9):1540-73. https://doi.org/10.1002/anie.200903924
83. Steinmetz NJ, Aisenbrey EA, Westbrook KK, Qi HJ, Bryant SJ. Mechanical loading regulates human MSC differentiation in a multi-layer hydrogel for osteochondral tissue engineering. Acta Biomater 2015;21:142-53. https://doi.org/10.1016/j.actbio.2015.04.015
84. Hoemann C, Kandel R, Roberts S, Saris DB, Creemers L, Mainil-Varlet P, et al. International Cartilage Repair Society (ICRS) Recommended Guidelines for Histological Endpoints for Cartilage Repair Studies in Animal Models and Clinical Trials. Cartilage 2011;2(2):153-72. https://doi.org/10.1177/1947603510397535
85. Pascual-Garrido C, Aisenbrey EA, Rodriguez-Fontan F, Payne KA, Bryant SJ, Goodrich LR. Photopolymerizable injectable cartilage mimetic hydrogel for the treatment of focal chondral lesions: aproof of concept study in a rabbit animal model. Am J Sports Med 2019;47(1):212. https://doi.org/10.1177/0363546518808012
86. Orth P, Madry H. Complex and elementary histological scoring systems for articular cartilage repair. Histol Histopathol 2015;30(8):911-9. https://doi.org/10.14670/HH-11-620
87. He Y, Yang F, Zhao H, Gao Q, Xia B, Fu J. Research on the printability of hydrogels in 3D bioprinting. Sci Rep 2016;6:29977. https://doi.org/10.1038/srep29977
88. Guo X, Park H, Young S, Kretlow JD, van den Beucken JJ, Baggett LS, et al. Repair of osteochondral defects with biodegradable hydrogel composites encapsulating marrow mesenchymal stem cells in a rabbit model. Acta Biomater 2010;6(1):39-47. https://doi.org/10.1016/j.actbio.2009.07.041
89. Lim CT, Ren X, Afizah MH, Tarigan-Panjaitan S, Yang Z, Wu Y, et al. Repair of osteochondral defects with rehydrated freeze-dried oligo[poly(ethylene glycol) fumarate] hydrogels seeded with bone marrow mesenchymal stem cells in a porcine model. Tissue Eng Part A 2013;19(15-16):1852-61. https://doi.org/10.1089/ten.TEA.2012.0621
90. Lam J, Lu S, Lee EJ, Trachtenberg JE, Meretoja VV, Dahlin RL, et al. Osteochondral defect repair using bilayered hydrogels encapsulating both chondrogenically and osteogenically pre-differentiated mesenchymal stem cells in a rabbit model. Osteoarthritis Cartilage 2014;22(9):1291-300. https://doi.org/10.1016/j.joca.2014.06.035
91. Saxena V, Kim M, Keah NM, Neuwirth AL, Stoeckl BD, Bickard K, et al. Anatomic mesenchymal stem cell-based engineered cartilage constructs for biologic total joint replacement. Tissue Eng Part A 2016;22(3-4):386-95. https://doi.org/10.1089/ten.tea.2015.0384
92. Lespasio MJ, Piuzzi NS, Husni ME, Muschler GF, Guarino A, MA M. Knee osteoarthritis: A primer. Perm J 2017;21:16-183. https://doi.org/10.7812/TPP/16-183
93. Lespasio MJ, Sultan AA, Piuzzi NS, Khlopas A, Husni ME, Muschler GF, et al. Hip osteoarthritis: A primer. Perm J 2018;22:17-084. https://doi.org/10.7812/TPP/17-084
94. Iorio R, Robb WJ, Healy WL, Berry DJ, Hozack WJ, Kyle RF, et al. Orthopaedic surgeon workforce and volume assessment for total hip and knee replacement in the United States: preparing for an epidemic. J Bone Joint Surg Am 2008;90(7):1598-605. https://doi.org/10.2106/JBJS.H.00067
95. Moutos FT, Glass KA, Compton SA, Ross AK, Gersbach CA, Guilak F, et al. Anatomically shaped tissue-engineered cartilage with tunable and inducible anticytokine delivery for biological joint resurfacing. Proc Natl Acad Sci USA 2016;113(31):E4513-22. https://doi.org/10.1073/pnas.1601639113
96. Rowland CR, Colucci LA, Guilak F. Fabrication of anatomically-shaped cartilage constructs using decellularized cartilage-derived matrix scaffolds. Biomaterials 2016;91:57-72. https://doi.org/10.1016/j.biomaterials.2016.03.012
97. Rey-Rico A, Cucchiarini M, Madry H. Hydrogels for precision meniscus tissue engineering: a comprehensive review. Connect Tissue Res 2017;58(3-4):317-328. https://doi.org/10.1080/03008207.2016.1276576
98. Shaw N, Erickson C, Bryant SJ, Ferguson VL, Krebs MD, Hadley-Miller N, et al. Regenerative medicine approaches for the treatment of pediatric physeal injuries. Tissue Eng Part B Rev 2018;24(2):85-97. https://doi.org/10.1089/ten.TEB.2017.0274
99. Gibbs DM, Black CR, Dawson JI, Oreffo RO. A review of hydrogel use in fracture healing and bone regeneration. J Tissue Eng Regen Med 2016;10(3):187-98. https://doi.org/10.1002/term.1968
100. Pot MW, Gonzales VK, Buma P, IntHout J, van Kuppevelt TH, de Vries RBM, et al. Improved cartilage regeneration by implantation of acellular biomaterials after bone marrow stimulation: a systematic review and meta-analysis of animal studies. Peer J 2016;4:e2243. https://doi.org/10.7717/peerj.2243. eCollection 2016
101. Shive MS, Stanish WD, McCormack R, Forriol F, Mohtadi N, Pelet S, et al. BST-CarGel(R) treatment maintains cartilage repair superiority over microfracture at 5 years in a multicenter randomized controlled trial. Cartilage 2015;6(2):62-72. https://doi.org/10.1177/1947603514562064