Evolving functional hydrogel strategies for cartilage engineering: from fundamentals to functional regeneration

Aikang Li , Jingtao Huang , Jiaqing Chen , Liangbin Wu , Hui Zeng , Zhenhan Deng , Peng Liu , Jianjing Lin

Burns & Trauma ›› 2025, Vol. 13 ›› Issue (1) : tkaf041

PDF (3460KB)
Burns & Trauma ›› 2025, Vol. 13 ›› Issue (1) :tkaf041 DOI: 10.1093/burnst/tkaf041
Review
research-article
Evolving functional hydrogel strategies for cartilage engineering: from fundamentals to functional regeneration
Author information +
History +
PDF (3460KB)

Abstract

Articular cartilage injury is a significant concern in osteoarthritis (OA), and while traditional pharmacological treatments and surgical interventions have provided some pain relief and promoted cartilage regeneration to a certain extent, long-term therapeutic outcomes remain suboptimal. The advancement of cartilage tissue engineering has introduced novel perspectives for cartilage regeneration. Hydrogel scaffolds, as crucial components in tissue functionality, have evolved from their initial role of physical coverage or single functionality to current combinations of diverse functionalities. This review thoroughly examines recent applications of functional hydrogels in cartilage regeneration. This article begins by discussing essential background information, including treatment strategies for cartilage defects and the fundamental characteristics of hydrogels. Next, within the framework of cartilage tissue engineering, we analyse five categories of functional hydrogels, emphasizing their distinctive physicochemical properties, drug delivery capabilities, and stimulus-responsive features for cartilage repair. The discussion extends to their mechanisms of action, classification, and limitations. Clinical products related to hydrogels in this field are also summarized. Finally, recommendations are offered to address current challenges and future directions in the development of functional hydrogels for cartilage regeneration.

Keywords

Osteoarthritis / Cartilage tissue engineering / Functional hydrogel / Cartilage regeneration

Cite this article

Download citation ▾
Aikang Li, Jingtao Huang, Jiaqing Chen, Liangbin Wu, Hui Zeng, Zhenhan Deng, Peng Liu, Jianjing Lin. Evolving functional hydrogel strategies for cartilage engineering: from fundamentals to functional regeneration. Burns & Trauma, 2025, 13 (1) : tkaf041 DOI:10.1093/burnst/tkaf041

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Tang X, Wang S, Zhan S, Niu J, Tao K, Zhang Y, et al. The prevalence of symptomatic knee osteoarthritis in China: results from the China health and retirement longitudinal study. Arthritis Rheumatol Hoboken NJ. 2016; 68: 648-53. https://doi.org/10.1002/art.39465.

[2]

Sharma L.Osteoarthritis of the knee. N Engl J Med. 2021; 384: 51-9. https://doi.org/10.1056/NEJMcp1903768.

[3]

Armiento AR, Stoddart MJ, Alini M, Eglin D. Biomaterials for articular cartilage tissue engineering: learning from biology. Acta Biomater. 2018; 65: 1-20. https://doi.org/10.1016/j.actbio.2017.11.021.

[4]

Cucchiarini M, Madry H. Biomaterial-guided delivery of gene vectors for targeted articular cartilage repair. Nat Rev Rheumatol. 2019; 15: 18-29. https://doi.org/10.1038/s41584-018-0125-2.

[5]

Katz JN, Arant KR, Loeser RF. Diagnosis and treatment of hip and knee osteoarthritis: a review. JAMA. 2021; 325: 568-78. https://doi.org/10.1001/jama.2020.22171.

[6]

Gou GH, Tseng FJ, Wang SH, Chen PJ, Shyu JF, Weng CF, et al. Autologous chondrocyte implantation versus microfracture in the knee: a meta-analysis and systematic review. Arthrosc J Arthrosc Relat Surg Off Publ Arthrosc Assoc N Am Int Arthrosc Assoc. 2020; 36: 289-303. https://doi.org/10.1016/j.arthro.2019.06.033.

[7]

Wei W, Dai H. Articular cartilage and osteochondral tissue engineering techniques: recent advances and challenges. Bioact Mater. 2021; 6: 4830-55. https://doi.org/10.1016/j.bioactmat.2021.05.011.

[8]

Wei W, Ma Y, Yao X, Zhou W, Wang X, Li C, et al. Advanced hydrogels for the repair of cartilage defects and regeneration. Bioact Mater. 2021; 6: 998-1011. https://doi.org/10.1016/j.bioactmat.2020.09.030.

[9]

Wu J, Chen Q, Deng C, Xu B, Zhang Z, Yang Y, et al. Exquisite design of injectable hydrogels in cartilage repair. Theranostics. 2020; 10: 9843-64. https://doi.org/10.7150/thno.46450.

[10]

Zhang W, Zha K, Hu W, Xiong Y, Knoedler S, Obed D, et al. Multifunctional hydrogels: advanced therapeutic tools for osteochondral regeneration. Biomater Res. 2023; 27: 76. https://doi.org/10.1186/s40824-023-00411-9.

[11]

Evans CH, Kraus VB, Setton LA. Progress in intra-articular therapy. Nat Rev Rheumatol. 2014; 10: 11-22. https://doi.org/10.1038/nrrheum.2013.159.

[12]

Bannuru RR, Schmid CH, Kent DM, Vaysbrot EE, Wong JB, McAlindon TE. Comparative effectiveness of pharmacologic interventions for knee osteoarthritis: a systematic review and network meta-analysis. Ann Intern Med. 2015; 162: 46-54. https://doi.org/10.7326/M14-1231.

[13]

Jones IA, Togashi R, Wilson ML, Heckmann N, Vangsness CT. Intra-articular treatment options for knee osteoarthritis. Nat Rev Rheumatol. 2019; 15: 77-90. https://doi.org/10.1038/s41584-018-0123-4.

[14]

Gerwin N, Hops C, Lucke A. Intraarticular drug delivery in osteoarthritis. Adv Drug Deliv Rev. 2006; 58: 226-42. https://doi.org/10.1016/j.addr.2006.01.018.

[15]

Lin C, Deng Z, Xiong J, Lu W, Chen K, Zheng Y, et al. The arthroscopic application of radiofrequency in treatment of articular cartilage lesions. Front Bioeng Biotechnol. 2021; 9: 822286. https://doi.org/10.3389/fbioe.2021.822286.

[16]

Wong CC, Chen CH, Chiu LH, Tsuang YH, Bai MY, Chung RJ, et al. Facilitating In vivo articular cartilage repair by tissue-engineered cartilage grafts produced from auricular chondrocytes. Am J Sports Med. 2018; 46: 713-27. https://doi.org/10.1177/0363546517741306.

[17]

Chimutengwende-Gordon M, Donaldson J, Bentley G. Current solutions for the treatment of chronic articular cartilage defects in the knee. EFORT Open Rev. 2020; 5: 156-63. https://doi.org/10.1302/2058-5241.5.190031.

[18]

Wong CC, Chen CH, Chiu LH, Tsuang YH, Bai MY, Chung RJ, et al. Facilitating In vivo articular cartilage repair by tissue-engineered cartilage grafts produced from auricular chondrocytes. Am J Sports Med. 2018; 46: 713-27. https://doi.org/10.1177/0363546517741306.

[19]

Pourjabbar B, Shams F, Moghadam M, Ahani-Nahayati M, Azari A, Sefat F, et al. Recent emerging trend in stem cell therapy risk factors. Curr Stem Cell Res Ther. 2023; 18: 1076-89. https://doi.org/10.2174/1574888X18666221223104859.

[20]

Yang Z, Li H, Yuan Z, Fu L, Jiang S, Gao C, et al. Endogenous cell recruitment strategy for articular cartilage regeneration. Acta Biomater. 2020; 114: 31-52. https://doi.org/10.1016/j.actbio.2020.07.008.

[21]

Bian L, Zhai DY, Tous E, Rai R, Mauck RL, Burdick JA. Enhanced MSC chondrogenesis following delivery of TGF-β3 from alginate microspheres within hyaluronic acid hydrogels in vitro and in vivo. Biomaterials. 2011; 32: 6425-34. https://doi.org/10.1016/j.biomaterials.2011.05.033.

[22]

Lu S, Lam J, Trachtenberg JE, Lee EJ, Seyednejad H, van den Beucken JJJP, et al. Dual growth factor delivery from bilayered, biodegradable hydrogel composites for spatially-guided osteochondral tissue repair. Biomaterials. 2014; 35: 8829-39. https://doi.org/10.1016/j.biomaterials.2014.07.006.

[23]

Xie Y, Zinkle A, Chen L, Mohammadi M. Fibroblast growth factor signalling in osteoarthritis and cartilage repair. Nat Rev Rheumatol. 2020; 16: 547-64. https://doi.org/10.1038/s41584-020-0469-2.

[24]

Zheng Z, Sun J, Wang J, He S, Huang Y, Yang X, et al. A negative feedback bionic hydrogel reverses damaged cartilage microenvironment and induces targeted BMSCs differentiation for cartilage regeneration. Chem Eng J. 2023; 473: 145228. https://doi.org/10.1016/j.cej.2023.145228.

[25]

Hou KT, Liu TY, Chiang MY, Chen CY, Chang SJ, Chen SY. Cartilage tissue-mimetic pellets with multifunctional magnetic hyaluronic acid-graft-amphiphilic Gelatin microcapsules for chondrogenic stimulation. Polymers. 2020; 12: 785. https://doi.org/10.3390/polym12040785.

[26]

Wu S, Zhang H, Wang S, Sun J, Hu Y, Liu H, et al. Ultrasound-triggered in situ gelation with ROS-controlled drug release for cartilage repair. Mater Horiz. 2023; 10: 3507-22. https://doi.org/10.1039/D3MH00042G.

[27]

Lin J, Li K, Yang Z, Cao F, Gao L, Ning T, et al. Functionally improved mesenchymal stem cells via nanosecond pulsed electric fields for better treatment of osteoarthritis. J Orthop Transl. 2024; 47: 235-48. https://doi.org/10.1016/j.jot.2024.03.006.

[28]

Ding X, Gao J, Yu X, Shi J, Chen J, Yu L, et al. 3D-printed porous scaffolds of hydrogels modified with TGF-β1 binding peptides to promote In vivo cartilage regeneration and animal gait restoration. ACS Appl Mater Interfaces. 2022; 14: 15982-95. https://doi.org/10.1021/acsami.2c00761.

[29]

Qasim M, Chae DS, Lee NY. Advancements and frontiers in nano-based 3D and 4D scaffolds for bone and cartilage tissue engineering. Int J Nanomedicine. 2019; 14: 4333-51. https://doi.org/10.2147/IJN.S209431.

[30]

Lin J, Jia S, Cao F, Huang J, Chen J, Wang J, et al. Research progress on injectable microspheres as new strategies for the treatment of osteoarthritis through promotion of cartilage repair. Adv Funct Mater. 2024; 34: 2400585. https://doi.org/10.1002/adfm.202400585.

[31]

Lv Z, Ji Y, Wen G, Liang X, Zhang K, Zhang W. Structure-optimized and microenvironment-inspired nanocomposite biomaterials in bone tissue engineering. Burns Trauma. 2024; 12: tkae036. https://doi.org/10.1093/burnst/tkae036.

[32]

Yang X, Li S, Ren Y, Qiang L, Liu Y, Wang J, et al. 3D printed hydrogel for articular cartilage regeneration. Compos Part B Eng. 2022; 237: 109863. https://doi.org/10.1016/j.compositesb.2022.109863.

[33]

Kim IL, Mauck RL, Burdick JA. Hydrogel design for cartilage tissue engineering: a case study with hyaluronic acid. Biomaterials. 2011; 32: 8771-82. https://doi.org/10.1016/j.biomaterials.2011.08.073.

[34]

Zheng K, Zheng X, Yu M, He Y, Wu D. BMSCs-seeded interpenetrating network GelMA/SF composite hydrogel for articular cartilage repair. J Funct Biomater. 2023; 14: 39. https://doi.org/10.3390/jfb14010039.

[35]

Xu Y, Xu Y, Bi B, Hou M, Yao L, Du Q, et al. A moldable thermosensitive hydroxypropyl chitin hydrogel for 3D cartilage regeneration in vitro and in vivo. Acta Biomater. 2020; 108: 87-96. https://doi.org/10.1016/j.actbio.2020.03.039.

[36]

Panda AK, Basu B. Functionalized fluoropolymer-compatibilized elastomeric bilayer composites for osteochondral repair: Unraveling the role of substrate stiffness and functionalities. ACS Appl Bio Mater. 2021; 4: 8543-58. https://doi.org/10.1021/acsabm.1c01021.

[37]

Zeng D, Chen Y, Liao Z, Wei G, Huang X, Liang R, et al. Cartilage organoids and osteoarthritis research: a narrative review. Front Bioeng Biotechnol. 2023; 11: 1278692. https://doi.org/10.3389/fbioe.2023.1278692.

[38]

Chen S, Chen X, Geng Z, Su J. The horizon of bone organoid: a perspective on construction and application. Bioact Mater. 2022; 18: 15-25. https://doi.org/10.1016/j.bioactmat.2022.01.048.

[39]

Huang J, Li A, Liang R, Wu X, Jia S, Chen J, et al. Future perspectives: advances in bone/cartilage organoid technology and clinical potential. Biomater Transl. 2024; 5: 425-43.

[40]

Yang Z, Wang B, Liu W, Li X, Liang K, Fan Z, et al. In situ self-assembled organoid for osteochondral tissue regeneration with dual functional units. Bioact Mater. 2023; 27: 200-15. https://doi.org/10.1016/j.bioactmat.2023.04.002.

[41]

Abe K, Yamashita A, Morioka M, Horike N, Takei Y, Koyamatsu S, et al. Engraftment of allogeneic iPS cell-derived cartilage organoid in a primate model of articular cartilage defect. Nat Commun. 2023; 14: 804. https://doi.org/10.1038/s41467-023-36408-0.

[42]

Li A, Liang R, Sheng W, Wu X, Guo W, Liu P, et al. Global research trends in bone/cartilage organoids from 2010 to 2024: a bibliometric and visualization study. Organoid Res. 2025; 0: 8295.

[43]

Hernandez JL, Woodrow KA. Medical applications of porous biomaterials: features of porosity and tissue-specific implications for biocompatibility. Adv Healthc Mater. 2022; 11: e2102087. https://doi.org/10.1002/adhm.202102087.

[44]

Gao F, Xu Z, Liang Q, Li H, Peng L, Wu M, et al. Osteochondral regeneration with 3D-printed biodegradable high-strength supramolecular polymer reinforced-Gelatin hydrogel scaffolds. Adv Sci Weinh Baden-Wurtt Ger. 2019; 6: 1900867. https://doi.org/10.1002/advs.201900867.

[45]

Yi Y, Xie C, Liu J, Zheng Y, Wang J, Lu X. Self-adhesive hydrogels for tissue engineering. J Mater Chem B. 2021; 9: 8739-67. https://doi.org/10.1039/D1TB01503F.

[46]

Tang X, Fan L, Pei M, Zeng L, Ge Z. Evolving concepts of chondrogenic differentiation: history, state-of-the-art and future perspectives. Eur Cell Mater. 2015; 30: 12-27. https://doi.org/10.22203/eCM.v030a02.

[47]

Zhao Y, Hu M, Gong Y, Zhao Y, Shen Z. Preparation of mechanically stable self-assembled peptides hydrogels. J Vis Exp JoVE. 2024, 10.3791/67267. https://doi.org/10.3791/67267.

[48]

Yang Y, Hu Q, Shao Q, Peng Y, Yu B, Luo F, et al. A baicalin-based functional polymer in dynamic reversible networks alleviates osteoarthritis by cellular interactions. Adv Sci Weinh Baden-Wurtt Ger. 2025; 12: e2410951. https://doi.org/10.1002/advs.202410951.

[49]

Ziadlou R, Rotman S, Teuschl A, Salzer E, Barbero A, Martin I, et al. Optimization of hyaluronic acid-tyramine/silk-fibroin composite hydrogels for cartilage tissue engineering and delivery of anti-inflammatory and anabolic drugs. Mater Sci Eng C Mater Biol Appl. 2021; 120: 111701. https://doi.org/10.1016/j.msec.2020.111701.

[50]

Hua Y, Huo Y, Bai B, Hao J, Hu G, Ci Z, et al. Fabrication of biphasic cartilage-bone integrated scaffolds based on tissue-specific photo-crosslinkable acellular matrix hydrogels. Mater Today Bio. 2022; 17: 100489. https://doi.org/10.1016/j.mtbio.2022.100489.

[51]

Chen N, Li S, Miao C, Zhao Q, Dong J, Li L, et al. Polysaccharide-based hydrogels for cartilage regeneration. Front Cell Dev Biol. 2024; 12: 1444358. https://doi.org/10.3389/fcell.2024.1444358.

[52]

Kang LJ, Yoon J, Rho JG, Han HS, Lee S, Oh YS, et al. Self-assembled hyaluronic acid nanoparticles for osteoarthritis treatment. Biomaterials. 2021; 275: 120967. https://doi.org/10.1016/j.biomaterials.2021.120967.

[53]

Zhang M, Yang M, Woo MW, Li Y, Han W, Dang X. High-mechanical strength carboxymethyl chitosan-based hydrogel film for antibacterial wound dressing. Carbohydr Polym. 2021; 256: 117590. https://doi.org/10.1016/j.carbpol.2020.117590.

[54]

Recha-Sancho L, Semino CE. Chondroitin Sulfate-and Decorin-based self-assembling scaffolds for cartilage tissue engineering. PLoS One. 2016; 11: e0157603. https://doi.org/10.1371/journal.pone.0157603.

[55]

Chen F, Yu S, Liu B, Ni Y, Yu C, Su Y, et al. An injectable enzymatically crosslinked carboxymethylated pullulan/chondroitin Sulfate hydrogel for cartilage tissue engineering. Sci Rep. 2016; 6: 20014. https://doi.org/10.1038/srep20014.

[56]

Kouki M, Varshosaz J, Hashemibeni B, Sarmadi A. Injectable gellan gum/lignocellulose nanofibrils hydrogels enriched with melatonin loaded forsterite nanoparticles for cartilage tissue engineering: fabrication, characterization and cell culture studies. Mater Sci Eng C. 2020; 115: 111114. https://doi.org/10.1016/j.msec.2020.111114.

[57]

Bonifacio MA, Cometa S, Cochis A, Scalzone A, Gentile P, Scalia AC, et al. A bioprintable gellan gum/lignin hydrogel: a smart and sustainable route for cartilage regeneration. Int J Biol Macromol. 2022; 216: 336-46. https://doi.org/10.1016/j.ijbiomac.2022.07.002.

[58]

Gan D, Wang Z, Xie C, Wang X, Xing W, Ge X, et al. Mussel-inspired tough hydrogel with In situ nanohydroxyapatite mineralization for osteochondral defect repair. Adv Healthc Mater. 2019; 8: e1901103. https://doi.org/10.1002/adhm.201901103.

[59]

Haghighi P, Shamloo A. Fabrication of a novel 3D scaffold for cartilage tissue repair: In-vitro and in-vivo study. Mater Sci Eng C Mater Biol Appl. 2021; 128: 112285. https://doi.org/10.1016/j.msec.2021.112285.

[60]

Singh BN, Nallakumarasamy A, Sinha S, Rastogi A, Mallick SP, Divakar S, et al. Generation of hybrid tissue engineered construct through embedding autologous chondrocyte loaded platelet rich plasma/alginate based hydrogel in porous scaffold for cartilage regeneration. Int J Biol Macromol. 2022; 203: 389-405. https://doi.org/10.1016/j.ijbiomac.2022.01.054.

[61]

Zhu Z, Ling S, Yeo J, Zhao S, Tozzi L, Buehler MJ, et al. High-strength, durable all-silk fibroin hydrogels with versatile processability toward multifunctional applications. Adv Funct Mater. 2018; 28: 1704757. https://doi.org/10.1002/adfm.201704757.

[62]

Yuan T, Li Z, Zhang Y, Shen K, Zhang X, Xie R, et al. Injectable ultrasonication-induced silk fibroin hydrogel for cartilage repair and regeneration. Tissue Eng Part A. 2021; 27: 1213-24. https://doi.org/10.1089/ten.tea.2020.0323.

[63]

Cipriani F, Ariño Palao B, Gonzalez de Torre I, Vega Castrillo A, Aguado Hernández HJ, Alonso Rodrigo M, et al. An elastin-like recombinamer-based bioactive hydrogel embedded with mesenchymal stromal cells as an injectable scaffold for osteochondral repair. Regen Biomater. 2019; 6: 335-47. https://doi.org/10.1093/rb/rbz023.

[64]

Fussenegger M, Meinhart J, Höbling W, Kullich W, Funk S, Bernatzky G. Stabilized autologous fibrin-chondrocyte constructs for cartilage repair in vivo. Ann Plast Surg. 2003; 51: 493-8. https://doi.org/10.1097/01.sap.0000067726.32731.E1.

[65]

Chen C, Wu D, Wang Z, Liu L, He J, Li J, et al. Peptide-based hydrogel scaffold facilitates articular cartilage damage repair. ACS Appl Mater Interfaces. 2024; 16: 11336-48. https://doi.org/10.1021/acsami.4c00811.

[66]

Yu P, Ma Y, Zhu Y, Pei J, Zheng G, Liu Y, et al. Transforming growth factor-β1-loaded RADA-16 hydrogel scaffold for effective cartilage regeneration. Colloids Surf B Biointerfaces. 2024; 239: 113959. https://doi.org/10.1016/j.colsurfb.2024.113959.

[67]

Chen Z, Zhang Q, Li H, Wei Q, Zhao X, Chen F. Elastin-like polypeptide modified silk fibroin porous scaffold promotes osteochondral repair. Bioact Mater. 2021; 6: 589-601. https://doi.org/10.1016/j.bioactmat.2020.09.003.

[68]

Kambe Y, Yamamoto K, Kojima K, Tamada Y, Tomita N. Effects of RGDS sequence genetically interfused in the silk fibroin light chain protein on chondrocyte adhesion and cartilage synthesis. Biomaterials. 2010; 31: 7503-11. https://doi.org/10.1016/j.biomaterials.2010.06.045.

[69]

Parmar PA, St-Pierre JP, Chow LW, Spicer CD, Stoichevska V, Peng YY, et al. Enhanced articular cartilage by human mesenchymal stem cells in enzymatically mediated transiently RGDS-functionalized collagen-mimetic hydrogels. Acta Biomater. 2017; 51: 75-88. https://doi.org/10.1016/j.actbio.2017.01.028.

[70]

Haq-Siddiqi NA, Britton D, Kim MJ. Protein-engineered biomaterials for cartilage therapeutics and repair. Adv Drug Deliv Rev. 2023; 192: 114647. https://doi.org/10.1016/j.addr.2022.114647.

[71]

Lv X, Sun C, Hu B, Chen S, Wang Z, Wu Q, et al. Simultaneous recruitment of stem cells and chondrocytes induced by a functionalized self-assembling peptide hydrogel improves endogenous cartilage regeneration. Front Cell Dev Biol. 2020; 8: 864. https://doi.org/10.3389/fcell.2020.00864.

[72]

Yan X, Yang B, Chen Y, Song Y, Ye J, Pan Y, et al. Anti-friction MSCs delivery system improves the therapy for severe osteoarthritis. Adv Mater. 2021; 33:e2104758. https://doi.org/10.1002/adma.202104758.

[73]

Zhang C, Huang H, Chen J, Zuo T, Ou Q, Ruan G, et al. DNA supramolecular hydrogel-enabled sustained delivery of metformin for relieving osteoarthritis. ACS Appl Mater Interfaces. 2023; 15: 16369-79. https://doi.org/10.1021/acsami.2c20496.

[74]

Shen C, Wang J, Li G, Hao S, Wu Y, Song P, et al. Boosting cartilage repair with silk fibroin-DNA hydrogel-based cartilage organoid precursor. Bioact Mater. 2024; 35: 429-44. https://doi.org/10.1016/j.bioactmat.2024.02.016.

[75]

Zhou Z, Song P, Wu Y, Wang M, Shen C, Ma Z, et al. Dual-network DNA-silk fibroin hydrogels with controllable surface rigidity for regulating chondrogenic differentiation. Mater Horiz. 2024; 11: 1465-83. https://doi.org/10.1039/D3MH01581E.

[76]

Shi J, Yu L, Ding J. PEG-based thermosensitive and biodegradable hydrogels. Acta Biomater. 2021; 128: 42-59. https://doi.org/10.1016/j.actbio.2021.04.009.

[77]

Kim TH, An DB, Oh SH, Kang MK, Song HH, Lee JH. Creating stiffness gradient polyvinyl alcohol hydrogel using a simple gradual freezing-thawing method to investigate stem cell differentiation behaviors. Biomaterials. 2015; 40: 51-60. https://doi.org/10.1016/j.biomaterials.2014.11.017.

[78]

Xiang D, Cui Y, Wan Z, Wang S, Peng L, Liao Z, et al. Study on swelling, compression property and degradation stability of PVA composite hydrogels for artificial nucleus pulposus. J Mech Behav Biomed Mater. 2022; 136: 105496. https://doi.org/10.1016/j.jmbbm.2022.105496.

[79]

Du Y, Liu H, Yang Q, Wang S, Wang J, Ma J, et al. Selective laser sintering scaffold with hierarchical architecture and gradient composition for osteochondral repair in rabbits. Biomaterials. 2017; 137: 37-48. https://doi.org/10.1016/j.biomaterials.2017.05.021.

[80]

Chen CH, Lee MY, Shyu VBH, Chen YC, Chen CT, Chen JP. Surface modification of polycaprolactone scaffolds fabricated via selective laser sintering for cartilage tissue engineering. Mater Sci Eng C. 2014; 40: 389-97. https://doi.org/10.1016/j.msec.2014.04.029.

[81]

Yan S, Zhang X, Zhang K, Di H, Feng L, Li G, et al. Injectable in situ forming poly(L-glutamic acid) hydrogels for cartilage tissue engineering. J Mater Chem B. 2016; 4: 947-61. https://doi.org/10.1039/C5TB01488C.

[82]

Li S, Niu D, Shi T, Yun W, Yan S, Xu G, et al. Injectable, In situ self-cross-linking, self-healing poly(l-glutamic acid)/polyethylene glycol hydrogels for cartilage tissue engineering. ACS Biomater Sci Eng. 2023; 9: 2625-35. https://doi.org/10.1021/acsbiomaterials.3c00041.

[83]

Olubamiji AD, Izadifar Z, Si JL, Cooper DML, Eames BF, Chen DXB. Modulating mechanical behaviour of 3D-printed cartilage-mimetic PCL scaffolds: influence of molecular weight and pore geometry. Biofabrication. 2016; 8: 025020. https://doi.org/10.1088/1758-5090/8/2/025020.

[84]

Della Sala F, Biondi M, Guarnieri D, Borzacchiello A, Ambrosio L, Mayol L. Mechanical behavior of bioactive poly(ethylene glycol) diacrylate matrices for biomedical application. J Mech Behav Biomed Mater. 2020; 110: 103885. https://doi.org/10.1016/j.jmbbm.2020.103885.

[85]

Ingavle GC, Gehrke SH, Detamore MS. The bioactivity of agarose-PEGDA interpenetrating network hydrogels with covalently immobilized RGD peptides and physically entrapped aggrecan. Biomaterials. 2014; 35: 3558-70. https://doi.org/10.1016/j.biomaterials.2014.01.002.

[86]

Annabi N, Fathi A, Mithieux SM, Martens P, Weiss AS, Dehghani F. The effect of elastin on chondrocyte adhesion and proliferation on poly(ε-caprolactone)/elastin composites. Biomaterials. 2011; 32: 1517-25. https://doi.org/10.1016/j.biomaterials.2010.10.024.

[87]

Yang J, Jing X, Wang Z, Liu X, Zhu X, Lei T, et al. In vitro and in vivo study on an injectable glycol chitosan/Dibenzaldehyde-terminated polyethylene glycol hydrogel in repairing articular cartilage defects. Front Bioeng Biotechnol. 2021; 9: 607709. https://doi.org/10.3389/fbioe.2021.607709.

[88]

Wang L, Chen X, Wang S, Ma J, Yang X, Chen H, et al. Ferrous/ferric ions crosslinked type II collagen multifunctional hydrogel for advanced osteoarthritis treatment. Adv Healthc Mater. 2024; 13: e2302833.

[89]

Lin X, Liu R, Beitzel J, Zhou Y, Lagadon C, Zhang M. Injectable biodegradable chitosan-PEG/PEG-dialdehyde hydrogel for stem cell delivery and cartilage regeneration. Gels Basel Switz. 2024; 10: 508. https://doi.org/10.3390/gels10080508.

[90]

Paul S, Schrobback K, Tran PA, Meinert C, Davern JW, Weekes A, et al. Photo-cross-linkable, injectable, and highly adhesive GelMA-glycol chitosan hydrogels for cartilage repair. Adv Healthc Mater. 2023; 12:e2302078. https://doi.org/10.1002/adhm.202302078.

[91]

Feng Q, Lin S, Zhang K, Dong C, Wu T, Huang H, et al. Sulfated hyaluronic acid hydrogels with retarded degradation and enhanced growth factor retention promote hMSC chondrogenesis and articular cartilage integrity with reduced hypertrophy. Acta Biomater. 2017; 53: 329-42. https://doi.org/10.1016/j.actbio.2017.02.015.

[92]

D’Este M, Sprecher CM, Milz S, Nehrbass D, Dresing I, Zeiter S, et al. Evaluation of an injectable thermoresponsive hyaluronan hydrogel in a rabbit osteochondral defect model. J Biomed Mater Res A. 2016; 104: 1469-78. https://doi.org/10.1002/jbm.a.35673.

[93]

Liu X, Yang Y, Niu X, Lin Q, Zhao B, Wang Y, et al. An in situ photocrosslinkable platelet rich plasma-complexed hydrogel glue with growth factor controlled release ability to promote cartilage defect repair. Acta Biomater. 2017; 62: 179-87. https://doi.org/10.1016/j.actbio.2017.05.023.

[94]

Jin R, Moreira Teixeira LS, Dijkstra PJ, Karperien M, van Blitterswijk CA, Zhong ZY, et al. Injectable chitosan-based hydrogels for cartilage tissue engineering. Biomaterials. 2009; 30: 2544-51. https://doi.org/10.1016/j.biomaterials.2009.01.020.

[95]

Li P, Zong H, Li G, Shi Z, Yu X, Zhang K, et al. Building a poly(amino acid)/chitosan-based self-healing hydrogel via host-guest interaction for cartilage regeneration. ACS Biomater Sci Eng. 2023; 9: 4855-66. https://doi.org/10.1021/acsbiomaterials.2c01547.

[96]

Mauck RL, Yuan X, Tuan RS. Chondrogenic differentiation and functional maturation of bovine mesenchymal stem cells in long-term agarose culture. Osteoarthr Cartil. 2006; 14: 179-89. https://doi.org/10.1016/j.joca.2005.09.002.

[97]

Erickson IE, Huang AH, Chung C, Li RT, Burdick JA, Mauck RL. Differential maturation and structure-function relationships in mesenchymal stem cell-and chondrocyte-seeded hydrogels. Tissue Eng Part A. 2009; 15: 1041-52. https://doi.org/10.1089/ten.tea.2008.0099.

[98]

Mouw JK, Case ND, Guldberg RE, Plaas AHK, Levenston ME. Variations in matrix composition and GAG fine structure among scaffolds for cartilage tissue engineering. Osteoarthr Cartil. 2005; 13: 828-36. https://doi.org/10.1016/j.joca.2005.04.020.

[99]

Yu X, Li X, Kan L, Pan P, Wang X, Liu W, et al. Double network microcrystalline cellulose hydrogels with high mechanical strength and biocompatibility for cartilage tissue engineering scaffold. Int J Biol Macromol. 2023; 238: 124113. https://doi.org/10.1016/j.ijbiomac.2023.124113.

[100]

Bonifacio MA, Cometa S, Cochis A, Gentile P, Ferreira AM, Azzimonti B, et al. Antibacterial effectiveness meets improved mechanical properties: manuka honey/gellan gum composite hydrogels for cartilage repair. Carbohydr Polym. 2018; 198: 462-72. https://doi.org/10.1016/j.carbpol.2018.06.115.

[101]

Pulkkinen HJ, Tiitu V, Valonen P, Jurvelin JS, Lammi MJ, Kiviranta I. Engineering of cartilage in recombinant human type II collagen gel in nude mouse model in vivo. Osteoarthr Cartil. 2010; 18: 1077-87. https://doi.org/10.1016/j.joca.2010.05.004.

[102]

Huang B, Li P, Chen M, Peng L, Luo X, Tian G, et al. Hydrogel composite scaffolds achieve recruitment and chondrogenesis in cartilage tissue engineering applications. J Nanobiotechnology. 2022; 20: 25. https://doi.org/10.1186/s12951-021-01230-7.

[103]

Almeida HV, Eswaramoorthy R, Cunniffe GM, Buckley CT, O’Brien FJ, Kelly DJ. Fibrin hydrogels functionalized with cartilage extracellular matrix and incorporating freshly isolated stromal cells as an injectable for cartilage regeneration. Acta Biomater. 2016; 36: 55-62. https://doi.org/10.1016/j.actbio.2016.03.008.

[104]

Hong H, Seo YB, Kim DY, Lee JS, Lee YJ, Lee H, et al. Digital light processing 3D printed silk fibroin hydrogel for cartilage tissue engineering. Biomaterials. 2020; 232: 119679. https://doi.org/10.1016/j.biomaterials.2019.119679.

[105]

Zhu D, Wang H, Trinh P, Heilshorn SC, Yang F. Elastin-like protein-hyaluronic acid (ELP-HA) hydrogels with decoupled mechanical and biochemical cues for cartilage regeneration. Biomaterials. 2017; 127: 132-40. https://doi.org/10.1016/j.biomaterials.2017.02.010.

[106]

Cipriani F, Krüger M, de Torre IG, Sierra LQ, Rodrigo MA, Kock L, et al. Cartilage regeneration in Preannealed silk elastin-like Co-Recombinamers injectable hydrogel embedded with mature chondrocytes in an ex vivo culture platform. Biomacromolecules. 2018; 19: 4333-47. https://doi.org/10.1021/acs.biomac.8b01211.

[107]

Liu J, Song H, Zhang L, Xu H, Zhao X. Self-assembly-peptide hydrogels as tissue-engineering scaffolds for three-dimensional culture of chondrocytes in vitro. Macromol Biosci. 2010; 10: 1164-70. https://doi.org/10.1002/mabi.200900450.

[108]

Kopesky PW, Vanderploeg EJ, Sandy JS, Kurz B, Grodzinsky AJ. Self-assembling peptide hydrogels modulate in vitro chondrogenesis of bovine bone marrow stromal cells. Tissue Eng Part A. 2010; 16: 465-77. https://doi.org/10.1089/ten.tea.2009.0158.

[109]

Shi T, Niu D, You J, Li S, Li G, Ren K, et al. Injectable macro-porous chitosan/polyethylene glycol-silicotungstic acid double-network hydrogels based on “smashed gels recombination” strategy for cartilage tissue engineering. Int J Biol Macromol. 2023; 233: 123541. https://doi.org/10.1016/j.ijbiomac.2023.123541.

[110]

Oliveira AS, Silva JC, Figueiredo L, Ferreira FC, Kotov NA, Colaço R, et al. High-performance bilayer composites for the replacement of osteochondral defects. Biomater Sci. 2022; 10: 5856-75. https://doi.org/10.1039/D2BM00716A.

[111]

Zhu C, Huang C, Zhang W, Ding X, Yang Y. Biodegradable-glass-Fiber reinforced hydrogel composite with enhanced mechanical performance and cell proliferation for potential cartilage repair. Int J Mol Sci. 2022; 23: 8717. https://doi.org/10.3390/ijms23158717.

[112]

Skaalure SC, Dimson SO, Pennington AM, Bryant SJ. Semi-interpenetrating networks of hyaluronic acid in degradable PEG hydrogels for cartilage tissue engineering. Acta Biomater. 2014; 10: 3409-20. https://doi.org/10.1016/j.actbio.2014.04.013.

[113]

Chen YR, Yan X, Yuan FZ, Lin L, Wang SJ, Ye J, et al. Kartogenin-conjugated double-network hydrogel combined with stem cell transplantation and tracing for cartilage repair. Adv Sci Weinh Baden-Wurtt Ger. 2022; 9: e2105571. https://doi.org/10.1002/advs.202105571.

[114]

Ghandforoushan P, Hanaee J, Aghazadeh Z, Samiei M, Navali AM, Khatibi A, et al. Novel nanocomposite scaffold based on gelatin/PLGA-PEG-PLGA hydrogels embedded with TGF-β1 for chondrogenic differentiation of human dental pulp stem cells in vitro. Int J Biol Macromol. 2022; 201: 270-87. https://doi.org/10.1016/j.ijbiomac.2021.12.097.

[115]

Duarte Campos DF, Drescher W, Rath B, Tingart M, Fischer H. Supporting biomaterials for articular cartilage repair. Cartilage. 2012; 3: 205-21. https://doi.org/10.1177/1947603512444722.

[116]

Karami P, Martin R, Laurent A, Nam HY, Philippe V, Applegate LA, et al. An adhesive hydrogel Technology for Enhanced Cartilage Repair: a preliminary proof of concept. Gels Basel Switz. 2024; 10: 657. https://doi.org/10.3390/gels10100657.

[117]

Wu Y, Lyu Z, Hu F, Yang L, Yang K, Chen M, et al. A chondroitin sulphate hydrogel with sustained release of SDF-1α for extensive cartilage defect repair through induction of cell homing and promotion of chondrogenesis. J Mater Chem B. 2024; 12: 8672-87. https://doi.org/10.1039/D4TB00624K.

[118]

Tong Z, Ma Y, Liang Q, Lei T, Wu H, Zhang X, et al. An in situ forming cartilage matrix mimetic hydrogel scavenges ROS and ameliorates osteoarthritis after superficial cartilage injury. Acta Biomater. 2024; 187: 82-97. https://doi.org/10.1016/j.actbio.2024.08.018.

[119]

Li S, Niu D, Fang H, Chen Y, Li J, Zhang K, et al. Tissue adhesive, ROS scavenging and injectable PRP-based ‘plasticine’ for promoting cartilage repair. Regen Biomater. 2023; 11: rbad104. https://doi.org/10.1093/rb/rbad104.

[120]

Qiao Z, Lian M, Han Y, Sun B, Zhang X, Jiang W, et al. Bioinspired stratified electrowritten fiber-reinforced hydrogel constructs with layer-specific induction capacity for functional osteochondral regeneration. Biomaterials. 2021; 266: 120385. https://doi.org/10.1016/j.biomaterials.2020.120385.

[121]

Sun Y, You Y, Jiang W, Wang B, Wu Q, Dai K. 3D bioprinting dual-factor releasing and gradient-structured constructs ready to implant for anisotropic cartilage regeneration. Sci Adv. 2020; 6: eaay1422. https://doi.org/10.1126/sciadv.aay1422.

[122]

Liao J, Tian T, Shi S, Xie X, Ma Q, Li G, et al. The fabrication of biomimetic biphasic CAN-PAC hydrogel with a seamless interfacial layer applied in osteochondral defect repair. Bone Res. 2017; 5: 17018. https://doi.org/10.1038/boneres.2017.18.

[123]

Critchley S, Sheehy EJ, Cunniffe G, Diaz-Payno P, Carroll SF, Jeon O, et al. 3D printing of fibre-reinforced cartilaginous templates for the regeneration of osteochondral defects. Acta Biomater. 2020; 113: 130-43. https://doi.org/10.1016/j.actbio.2020.05.040.

[124]

Levingstone TJ, Matsiko A, Dickson GR, O’Brien FJ, Gleeson JP. A biomimetic multi-layered collagen-based scaffold for osteochondral repair. Acta Biomater. 2014; 10: 1996-2004. https://doi.org/10.1016/j.actbio.2014.01.005.

[125]

Yu L, Cavelier S, Hannon B, Wei M. Recent development in multizonal scaffolds for osteochondral regeneration. Bioact Mater. 2023; 25: 122-59. https://doi.org/10.1016/j.bioactmat.2023.01.012.

[126]

Chen H, Huang J, Li X, Zhao W, Hua Y, Song Z, et al. Trilayered biomimetic hydrogel scaffolds with dual-differential microenvironment for articular osteochondral defect repair. Mater Today Bio. 2024; 26: 101051. https://doi.org/10.1016/j.mtbio.2024.101051.

[127]

Fu L, Yang Z, Gao C, Li H, Yuan Z, Wang F, et al. Advances and prospects in biomimetic multilayered scaffolds for articular cartilage regeneration. Regen Biomater. 2020; 7: 527-42. https://doi.org/10.1093/rb/rbaa042.

[128]

Radhakrishnan J, Manigandan A, Chinnaswamy P, Subramanian A, Sethuraman S. Gradient nano-engineered in situ forming composite hydrogel for osteochondral regeneration. Biomaterials. 2018; 162: 82-98. https://doi.org/10.1016/j.biomaterials.2018.01.056.

[129]

Zhang H, Huang H, Hao G, Zhang Y, Ding H, Fan Z, et al. 3D printing hydrogel scaffolds with nanohydroxyapatite gradient to effectively repair osteochondral defects in rats. Adv Funct Mater. 2021; 31: 2006697. https://doi.org/10.1002/adfm.202006697.

[130]

Wang S, Qiu Y, Qu L, Wang Q, Zhou Q. Hydrogels for treatment of different degrees of osteoarthritis. Front Bioeng Biotechnol. 2022; 10: 858656. https://doi.org/10.3389/fbioe.2022.858656.

[131]

Cai R, Shan Y, Du F, Miao Z, Zhu L, Hang L, et al. Injectable hydrogels as promising in situ therapeutic platform for cartilage tissue engineering. Int J Biol Macromol. 2024; 261: 129537. https://doi.org/10.1016/j.ijbiomac.2024.129537.

[132]

Cai Z, Zhang H, Wei Y, Wu M, Fu A. Shear-thinning hyaluronan-based fluid hydrogels to modulate viscoelastic properties of osteoarthritis synovial fluids. Biomater Sci. 2019; 7: 3143-57. https://doi.org/10.1039/C9BM00298G.

[133]

Panda AK, Basu B. Functionalized fluoropolymer-compatibilized elastomeric bilayer composites for osteochondral repair: Unraveling the role of substrate stiffness and functionalities. ACS Appl Bio Mater. 2021; 4: 8543-58. https://doi.org/10.1021/acsabm.1c01021.

[134]

Schuiringa GH, Pastrama M, Ito K, van Donkelaar CC. Towards a load bearing hydrogel: a proof of principle in the use of osmotic pressure for biomimetic cartilage constructs. J Mech Behav Biomed Mater. 2023; 137: 105552. https://doi.org/10.1016/j.jmbbm.2022.105552.

[135]

Spiller KL, Maher SA, Lowman AM. Hydrogels for the repair of articular cartilage defects. Tissue Eng Part B Rev. 2011; 17: 281-99. https://doi.org/10.1089/ten.teb.2011.0077.

[136]

Wang DA, Varghese S, Sharma B, Strehin I, Fermanian S, Gorham J, et al. Multifunctional chondroitin sulphate for cartilage tissue-biomaterial integration. Nat Mater. 2007; 6: 385-92. https://doi.org/10.1038/nmat1890.

[137]

Shirzaei Sani E, Kheirkhah A, Rana D, Sun Z, Foulsham W, Sheikhi A, et al. Sutureless repair of corneal injuries using naturally derived bioadhesive hydrogels. Sci Adv. 2019; 5: eaav1281. https://doi.org/10.1126/sciadv.aav1281.

[138]

Qi C, Liu J, Jin Y, Xu L, Wang G, Wang Z, et al. Photocrosslinkable, injectable sericin hydrogel as 3D biomimetic extracellular matrix for minimally invasive repairing cartilage. Biomaterials. 2018; 163: 89-104. https://doi.org/10.1016/j.biomaterials.2018.02.016.

[139]

Lee CSD, Gleghorn JP, Won Choi N, Cabodi M, Stroock AD, Bonassar LJ. Integration of layered chondrocyte-seeded alginate hydrogel scaffolds. Biomaterials. 2007; 28: 2987-93. https://doi.org/10.1016/j.biomaterials.2007.02.035.

[140]

Pereira RC, Scaranari M, Castagnola P, Grandizio M, Azevedo HS, Reis RL, et al. Novel injectable gel (system) as a vehicle for human articular chondrocytes in cartilage tissue regeneration. J Tissue Eng Regen Med. 2009; 3: 97-106. https://doi.org/10.1002/term.145.

[141]

Bian L, Hou C, Tous E, Rai R, Mauck RL, Burdick JA. The influence of hyaluronic acid hydrogel crosslinking density and macromolecular diffusivity on human MSC chondrogenesis and hypertrophy. Biomaterials. 2013; 34: 413-21. https://doi.org/10.1016/j.biomaterials.2012.09.052.

[142]

Sorlier P, Denuzière A, Viton C, Domard A. Relation between the degree of acetylation and the electrostatic properties of chitin and chitosan. Biomacromolecules. 2001; 2: 765-72. https://doi.org/10.1021/bm015531+.

[143]

Hoemann CD, Sun J, Légaré A, McKee MD, Buschmann MD. Tissue engineering of cartilage using an injectable and adhesive chitosan-based cell-delivery vehicle. Osteoarthr Cartil. 2005; 13: 318-29. https://doi.org/10.1016/j.joca.2004.12.001.

[144]

Lee H, Dellatore SM, Miller WM, Messersmith PB. Mussel-inspired surface chemistry for multifunctional coatings. Science. 2007; 318: 426-30. https://doi.org/10.1126/science.1147241.

[145]

Han L, Wang M, Li P, Gan D, Yan L, Xu J, et al. Mussel-inspired tissue-adhesive hydrogel based on the polydopamine-chondroitin Sulfate complex for growth-factor-free cartilage regeneration. ACS Appl Mater Interfaces. 2018; 10: 28015-26. https://doi.org/10.1021/acsami.8b05314.

[146]

Feifei Z, Yi H, Xianzhu Z, Long Y, Jun L, Deming J, et al. Tough hydrogel with enhanced tissue integration and in situ forming capability for osteochondral defect repair. Appl Mater Today. 2018; 13: 32-44. https://doi.org/10.1016/j.apmt.2018.08.005.

[147]

Ni X, Xing X, Deng Y, Li Z. Applications of stimuli-responsive hydrogels in bone and cartilage regeneration. Pharmaceutics. 2023; 15: 982. https://doi.org/10.3390/pharmaceutics15030982.

[148]

Eyrich D, Brandl F, Appel B, Wiese H, Maier G, Wenzel M, et al. Long-term stable fibrin gels for cartilage engineering. Biomaterials. 2007; 28: 55-65. https://doi.org/10.1016/j.biomaterials.2006.08.027.

[149]

Mabry KM, Lawrence RL, Anseth KS. Dynamic stiffening of poly(ethylene glycol)-based hydrogels to direct valvular interstitial cell phenotype in a three-dimensional environment. Biomaterials. 2015; 49: 47-56. https://doi.org/10.1016/j.biomaterials.2015.01.047.

[150]

Yang Y, Wang X, Yang F, Wang L, Wu D. Highly elastic and Ultratough hybrid ionic-covalent hydrogels with Tunable structures and mechanics. Adv Mater Deerfield Beach Fla. 2018; 30: e1707071. https://doi.org/10.1002/adma.201707071.

[151]

Ji D, Choi S, Kim J. A hydrogel-film casting to fabricate platelet-reinforced polymer composite films exhibiting superior mechanical properties. Small Weinh Bergstr Ger. 2018; 14: e1801042. https://doi.org/10.1002/smll.201801042.

[152]

Filippidi E, Cristiani TR, Eisenbach CD, Waite JH, Israelachvili JN, Ahn BK, et al. Toughening elastomers using mussel-inspired iron-catechol complexes. Science. 2017; 358: 502-5. https://doi.org/10.1126/science.aao0350.

[153]

Ronken S, Wirz D, Daniels AU, Kurokawa T, Gong JP, Arnold MP. Double-network acrylamide hydrogel compositions adapted to achieve cartilage-like dynamic stiffness. Biomech Model Mechanobiol. 2013; 12: 243-8. https://doi.org/10.1007/s10237-012-0395-6.

[154]

Sun JY, Zhao X, Illeperuma WRK, Chaudhuri O, Oh KH, Mooney DJ, et al. Highly stretchable and tough hydrogels. Nature. 2012; 489: 133-6. https://doi.org/10.1038/nature11409.

[155]

Yang Y, Wang X, Yang F, Shen H, Wu D. A universal soaking strategy to convert composite hydrogels into extremely tough and rapidly recoverable double-network hydrogels. Adv Mater Deerfield Beach Fla. 2016; 28: 7178-84. https://doi.org/10.1002/adma.201601742.

[156]

Nonoyama T, Lee YW, Ota K, Fujioka K, Hong W, Gong JP.Instant thermal switching from soft hydrogel to rigid plastics inspired by thermophile proteins. Adv Mater Deerfield Beach Fla. 2020; 32: e1905878. https://doi.org/10.1002/adma.201905878.

[157]

Young SA, Riahinezhad H, Amsden BG. In situ-forming, mechanically resilient hydrogels for cell delivery. J Mater Chem B. 2019; 7: 5742-61. https://doi.org/10.1039/C9TB01398A.

[158]

Zhao C, Zhang P, Zhou J, Qi S, Yamauchi Y, Shi R, et al. Layered nanocomposites by shear-flow-induced alignment of nanosheets. Nature. 2020; 580: 210-5. https://doi.org/10.1038/s41586-020-2161-8.

[159]

Spiller KL, Liu Y, Holloway JL, Maher SA, Cao Y, Liu W, et al. 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 Off J Control Release Soc. 2012; 157: 39-45. https://doi.org/10.1016/j.jconrel.2011.09.057.

[160]

Lange J, Follak N, Nowotny T, Merk H. Ergebnisse der SaluCartilage-implantation bei viertgradigen Knorpelschäden im Bereich des Kniegelenks. Unfallchirurg. 2006; 109: 193-9. https://doi.org/10.1007/s00113-005-1025-x.

[161]

Affatato S, Bersaglia G, Foltran I, Taddei P, Fini G, Toni A. The performance of gamma-and EtO-sterilised UHWMPE acetabular cups tested under severe simulator conditions. Part 1: role of the third-body wear process. Biomaterials. 2002; 23: 4839-46. https://doi.org/10.1016/S0142-9612(02)00238-7.

[162]

Raghunath J, Rollo J, Sales KM, Butler PE, Seifalian AM. Biomaterials and scaffold design: key to tissue-engineering cartilage. Biotechnol Appl Biochem. 2007; 46: 73-84. https://doi.org/10.1042/BA20060134.

[163]

Wu J, Chen Q, Deng C, Xu B, Zhang Z, Yang Y, et al. Exquisite design of injectable hydrogels in cartilage repair. Theranostics. 2020; 10: 9843-64. https://doi.org/10.7150/thno.46450.

[164]

Bertsch P, Diba M, Mooney DJ, Leeuwenburgh SCG. Self-healing injectable hydrogels for tissue regeneration. Chem Rev. 2023; 123: 834-73. https://doi.org/10.1021/acs.chemrev.2c00179.

[165]

Criado-Gonzalez M, Wagner D, Rodon Fores J, Blanck C, Schmutz M, Chaumont A, et al. Supramolecular hydrogel induced by electrostatic interactions between polycation and phosphorylated-Fmoc-tripeptide. Chem Mater. 2020; 32: 1946-56. https://doi.org/10.1021/acs.chemmater.9b04823.

[166]

Peng YY, Cheng Q, Wu M, Wang W, Zhao J, Diaz-Dussan D, et al. Highly stretchable, self-healing, injectable and pH responsive hydrogel from multiple hydrogen bonding and boron-carbohydrate interactions. Gels. 2023; 9: 709. https://doi.org/10.3390/gels9090709.

[167]

Meng L, Shao C, Cui C, Xu F, Lei J, Yang J. Autonomous self-healing silk fibroin injectable hydrogels formed via surfactant-free hydrophobic association. ACS Appl Mater Interfaces. 2020; 12: 1628-39. https://doi.org/10.1021/acsami.9b19415.

[168]

Muir VG, Burdick JA. Chemically-modified biopolymers for the formation of biomedical hydrogels. Chem Rev. 2021; 121: 10908-49. https://doi.org/10.1021/acs.chemrev.0c00923.

[169]

Yavvari PS, Pal S, Kumar S, Kar A, Awasthi AK, Naaz A, et al. Injectable, self-healing chimeric catechol-Fe(III) hydrogel for localized combination cancer therapy. ACS Biomater Sci Eng. 2017; 3: 3404-13. https://doi.org/10.1021/acsbiomaterials.7b00741.

[170]

Zhuang WR, Wang Y, Cui PF, Xing L, Lee J, Kim D, et al. Applications of π-π stacking interactions in the design of drug-delivery systems. J Control Release. 2019; 294: 311-26. https://doi.org/10.1016/j.jconrel.2018.12.014.

[171]

Feng Q, Xu J, Zhang K, Yao H, Zheng N, Zheng L, et al. Dynamic and cell-Infiltratable hydrogels as injectable carrier of therapeutic cells and drugs for treating challenging bone defects. ACS Cent Sci. 2019; 5: 440-50. https://doi.org/10.1021/acscentsci.8b00764.

[172]

Soltani S, Emadi R, Javanmard SH, Kharaziha M, Rahmati A. Shear-thinning and self-healing nanohybrid alginate-graphene oxide hydrogel based on guest-host assembly. Int J Biol Macromol. 2021; 180: 311-23. https://doi.org/10.1016/j.ijbiomac.2021.03.086.

[173]

Kang J, Li Y, Qin Y, Huang Z, Wu Y, Sun L, et al. In situ deposition of drug and gene nanoparticles on a patterned supramolecular hydrogel to construct a directionally osteochondral plug. Nano-Micro Lett. 2023; 16: 18. https://doi.org/10.1007/s40820-023-01228-w.

[174]

Quadrado RFN, Macagnan KL, Moreira AS, Fajardo AR. Chitosan-based hydrogel crosslinked through an aza-Michael addition catalyzed by boric acid. Int J Biol Macromol. 2021; 193: 1032-42. https://doi.org/10.1016/j.ijbiomac.2021.11.075.

[175]

Flégeau K, Pace R, Gautier H, Rethore G, Guicheux J, Le Visage C, et al. Toward the development of biomimetic injectable and macroporous biohydrogels for regenerative medicine. Adv Colloid Interf Sci. 2017; 247: 589-609. https://doi.org/10.1016/j.cis.2017.07.012.

[176]

Tan H, Li H, Rubin JP, Marra KG.Controlled gelation and degradation rates of injectable hyaluronic acid-based hydrogels through a double crosslinking strategy. J Tissue Eng Regen Med. 2011; 5: 790-7. https://doi.org/10.1002/term.378.

[177]

Wang X, Li Z, Shi T, Zhao P, An K, Lin C, et al. Injectable dextran hydrogels fabricated by metal-free click chemistry for cartilage tissue engineering. Mater Sci Eng C Mater Biol Appl. 2017; 73: 21-30. https://doi.org/10.1016/j.msec.2016.12.053.

[178]

Moreira Teixeira LS, Feijen J, van Blitterswijk CA, Dijkstra PJ, Karperien M. Enzyme-catalyzed crosslinkable hydrogels: emerging strategies for tissue engineering. Biomaterials. 2012; 33: 1281-90. https://doi.org/10.1016/j.biomaterials.2011.10.067.

[179]

Taylor DL, in het Panhuis M. Self-healing hydrogels. Adv Mater. 2016; 28: 9060-93. https://doi.org/10.1002/adma.201601613.

[180]

Hillewaere XKD, Du Prez FE. Fifteen chemistries for autonomous external self-healing polymers and composites. Prog Polym Sci. 2015; 49-50: 121-53. https://doi.org/10.1016/j.progpolymsci.2015.04.004.

[181]

Toohey KS, Sottos NR, Lewis JA, Moore JS, White SR. Self-healing materials with microvascular networks. Nat Mater. 2007; 6: 581-5. https://doi.org/10.1038/nmat1934.

[182]

Ahn BK, Lee DW, Israelachvili JN, Waite JH. Surface-initiated self-healing of polymers in aqueous media. Nat Mater. 2014; 13: 867-72. https://doi.org/10.1038/nmat4037.

[183]

Haines-Butterick L, Rajagopal K, Branco M, Salick D, Rughani R, Pilarz M, et al. Controlling hydrogelation kinetics by peptide design for three-dimensional encapsulation and injectable delivery of cells. Proc Natl Acad Sci USA. 2007; 104: 7791-6. https://doi.org/10.1073/pnas.0701980104.

[184]

Xu J, Feng Q, Lin S, Yuan W, Li R, Li J, et al. Injectable stem cell-laden supramolecular hydrogels enhance in situ osteochondral regeneration via the sustained co-delivery of hydrophilic and hydrophobic chondrogenic molecules. Biomaterials. 2019; 210: 51-61. https://doi.org/10.1016/j.biomaterials.2019.04.031.

[185]

Jeznach O, Kołbuk D, Sajkiewicz P. Injectable hydrogels and nanocomposite hydrogels for cartilage regeneration. J Biomed Mater Res A. 2018; 106: 2762-76. https://doi.org/10.1002/jbm.a.36449.

[186]

Yu HT, Gu CZ, Chen JQ. MiR-9 facilitates cartilage regeneration of osteoarthritis in rabbits through regulating notch signaling pathway. Eur Rev Med Pharmacol Sci. 2019; 23: 5051-8. https://doi.org/10.26355/eurrev_201906_18168.

[187]

Heirani-Tabasi A, Hosseinzadeh S, Rabbani S, Ahmadi Tafti SH, Jamshidi K, Soufizomorrod M, et al. Cartilage tissue engineering by co-transplantation of chondrocyte extracellular vesicles and mesenchymal stem cells, entrapped in chitosan-hyaluronic acid hydrogel. Biomed Mater Bristol Engl. 2021; 16: 055003. https://doi.org/10.1088/1748-605X/ac0cbf.

[188]

Wang L, Chen X, Wang S, Ma J, Yang X, Chen H, et al. Ferrous/ferric ions crosslinked type II collagen multifunctional hydrogel for advanced osteoarthritis treatment. Adv Healthc Mater. 2024; 13: e2302833. https://doi.org/10.1002/adhm.202302833.

[189]

Xu Y, Wang JY, Meng T, Ma XW, Li H, Li K. Role of hydrogels in osteoarthritis: a comprehensive review. Int J Rheum Dis. 2023; 26: 2390-401. https://doi.org/10.1111/1756-185X.14968.

[190]

Muthu S, Korpershoek JV, Novais EJ, Tawy GF, Hollander AP, Martin I. Failure of cartilage regeneration: emerging hypotheses and related therapeutic strategies. Nat Rev Rheumatol. 2023; 19: 403-16. https://doi.org/10.1038/s41584-023-00979-5.

[191]

Daneshmandi L, Shah S, Jafari T, Bhattacharjee M, Momah D, Saveh-Shemshaki N, et al. Emergence of the stem cell Secretome in regenerative engineering. Trends Biotechnol. 2020; 38: 1373-84. https://doi.org/10.1016/j.tibtech.2020.04.013.

[192]

Manferdini C, Gabusi E, Saleh Y, Lenzi E, D’Atri G, Ricotti L, et al. Mesenchymal stromal cells laden in hydrogels for osteoarthritis cartilage regeneration: a systematic review from In vitro studies to clinical applications. Cells. 2022; 11: 3969. https://doi.org/10.3390/cells11243969.

[193]

Shi W, Fang F, Kong Y, Greer SE, Kuss M, Liu B, et al. Dynamic hyaluronic acid hydrogel with covalent linked gelatin as an antioxidative bioink for cartilage tissue engineering. Biofabrication. 2021; 14: 014107. https://doi.org/10.1088/1758-5090/ac42de.

[194]

Vaca-González JJ, Culma JJS, Nova LMH, Garzón-Alvarado DA. Anatomy, molecular structures, and hyaluronic acid-Gelatin injectable hydrogels as a therapeutic alternative for hyaline cartilage recovery: a review. J Biomed Mater Res B Appl Biomater. 2023; 111: 1705-22. https://doi.org/10.1002/jbm.b.35261.

[195]

Feng W, Zhu C, Miao R, Li D, Xiong X, Wang R, et al. Comparative efficacy of endogenous stem cells recruiting hydrogels and stem cell-loaded hydrogels in knee cartilage regeneration: a meta-analysis. Curr Stem Cell Res Ther. 2024; 19: 993-1008. https://doi.org/10.2174/1574888X19666230914123443.

[196]

Choi B, Kim S, Lin B, Wu BM, Lee M. Cartilaginous extracellular matrix-modified chitosan hydrogels for cartilage tissue engineering. ACS Appl Mater Interfaces. 2014; 6: 20110-21. https://doi.org/10.1021/am505723k.

[197]

Nguyen TPT, Li F, Shrestha S, Tuan RS, Thissen H, Forsythe JS, et al. Cell-laden injectable microgels: current status and future prospects for cartilage regeneration. Biomaterials. 2021; 279: 121214. https://doi.org/10.1016/j.biomaterials.2021.121214.

[198]

Chung C, Burdick JA. Engineering cartilage tissue. Adv Drug Deliv Rev. 2008; 60: 243-62. https://doi.org/10.1016/j.addr.2007.08.027.

[199]

Ng SS, Su K, Li C, Chan-Park MB, Wang DA, Chan V. Biomechanical study of the edge outgrowth phenomenon of encapsulated chondrocytic isogenous groups in the surface layer of hydrogel scaffolds for cartilage tissue engineering. Acta Biomater. 2012; 8: 244-52. https://doi.org/10.1016/j.actbio.2011.08.018.

[200]

Gong Y, Su K, Lau TT, Zhou R, Wang DA. Microcavitary hydrogel-mediating phase transfer cell culture for cartilage tissue engineering. Tissue Eng Part A. 2010; 16: 3611-22. https://doi.org/10.1089/ten.tea.2010.0219.

[201]

Zeng L, Yao Y, Wang D, Chen X. Effect of microcavitary alginate hydrogel with different pore sizes on chondrocyte culture for cartilage tissue engineering. Mater Sci Eng C. 2014; 34: 168-75. https://doi.org/10.1016/j.msec.2013.09.003.

[202]

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: 1-22. https://doi.org/10.1155/2018/9079538.

[203]

Sun Y, You Y, Jiang W, Zhai Z, Dai K. 3D-bioprinting a genetically inspired cartilage scaffold with GDF5-conjugated BMSC-laden hydrogel and polymer for cartilage repair. Theranostics. 2019; 9: 6949-61. https://doi.org/10.7150/thno.38061.

[204]

Duan P, Pan Z, Cao L, He Y, Wang H, Qu Z, et al. The effects of pore size in bilayered poly(lactide-co-glycolide) scaffolds on restoring osteochondral defects in rabbits. J Biomed Mater Res A. 2014; 102: 180-92. https://doi.org/10.1002/jbm.a.34683.

[205]

Im GI. Regeneration of articular cartilage using adipose stem cells. J Biomed Mater Res A. 2016; 104: 1830-44. https://doi.org/10.1002/jbm.a.35705.

[206]

Oliveira JT, Gardel LS, Rada T, Martins L, Gomes ME, Reis RL. Injectable gellan gum hydrogels with autologous cells for the treatment of rabbit articular cartilage defects. J Orthop Res Off Publ Orthop Res Soc. 2010; 28: 1193-9. https://doi.org/10.1002/jor.21114.

[207]

Im GI, Shin YW, Lee KB. Do adipose tissue-derived mesenchymal stem cells have the same osteogenic and chondrogenic potential as bone marrow-derived cells? Osteoarthr Cartil. 2005; 13: 845-53. https://doi.org/10.1016/j.joca.2005.05.005.

[208]

Xie X, Wang Y, Zhao C, Guo S, Liu S, Jia W, et al. Comparative evaluation of MSCs from bone marrow and adipose tissue seeded in PRP-derived scaffold for cartilage regeneration. Biomaterials. 2012; 33: 7008-18. https://doi.org/10.1016/j.biomaterials.2012.06.058.

[209]

Chung JY, Song M, Ha CW, Kim JA, Lee CH, Park YB. Comparison of articular cartilage repair with different hydrogel-human umbilical cord blood-derived mesenchymal stem cell composites in a rat model. Stem Cell Res Ther. 2014; 5: 39. https://doi.org/10.1186/scrt427.

[210]

Lee JC, Min HJ, Park HJ, Lee S, Seong SC, Lee MC. Synovial membrane-derived mesenchymal stem cells supported by platelet-rich plasma can repair osteochondral defects in a rabbit model. Arthrosc J Arthrosc Relat Surg Off Publ Arthrosc Assoc N Am Int Arthrosc Assoc. 2013; 29: 1034-46. https://doi.org/10.1016/j.arthro.2013.02.026.

[211]

He P, Fu J, Wang DA. Murine pluripotent stem cells derived scaffold-free cartilage grafts from a micro-cavitary hydrogel platform. Acta Biomater. 2016; 35: 87-97. https://doi.org/10.1016/j.actbio.2016.02.026.

[212]

Okita K, Ichisaka T, Yamanaka S. Generation of germline-competent induced pluripotent stem cells. Nature. 2007; 448: 313-7. https://doi.org/10.1038/nature05934.

[213]

Xu X, Shi D, Liu Y, Yao Y, Dai J, Xu Z, et al. In vivo repair of full-thickness cartilage defect with human iPSC-derived mesenchymal progenitor cells in a rabbit model. Exp Ther Med. 2017; 14: 239-45. https://doi.org/10.3892/etm.2017.4474.

[214]

Tsumaki N, Okada M, Yamashita A. iPS cell technologies and cartilage regeneration. Bone. 2015; 70: 48-54. https://doi.org/10.1016/j.bone.2014.07.011.

[215]

He X, Ma J, Jabbari E. Migration of marrow stromal cells in response to sustained release of stromal-derived factor-1alpha from poly(lactide ethylene oxide fumarate) hydrogels. Int J Pharm. 2010; 390: 107-16. https://doi.org/10.1016/j.ijpharm.2009.12.063.

[216]

Purcell BP, Elser JA, Mu A, Margulies KB, Burdick JA. Synergistic effects of SDF-1α chemokine and hyaluronic acid release from degradable hydrogels on directing bone marrow derived cell homing to the myocardium. Biomaterials. 2012; 33: 7849-57. https://doi.org/10.1016/j.biomaterials.2012.07.005.

[217]

Lee JM, Ryu JH, Kim EA, Jo S, Kim BS, Lee H, et al. Adhesive barrier/directional controlled release for cartilage repair by endogenous progenitor cell recruitment. Biomaterials. 2015; 39: 173-81. https://doi.org/10.1016/j.biomaterials.2014.11.006.

[218]

Park MS, Kim YH, Jung Y, Kim SH, Park JC, Yoon DS, et al. In situ recruitment of human bone marrow-derived mesenchymal stem cells using chemokines for articular cartilage regeneration. Cell Transplant. 2015; 24: 1067-83. https://doi.org/10.3727/096368914X681018.

[219]

Vainieri ML, Lolli A, Kops N, D’Atri D, Eglin D, Yayon A, et al. Evaluation of biomimetic hyaluronic-based hydrogels with enhanced endogenous cell recruitment and cartilage matrix formation. Acta Biomater. 2020; 101: 293-303. https://doi.org/10.1016/j.actbio.2019.11.015.

[220]

Labour MN, Riffault M, Christensen ST, Hoey DA. TGFβ1-induced recruitment of human bone mesenchymal stem cells is mediated by the primary cilium in a SMAD3-dependent manner. Sci Rep. 2016; 6: 35542. https://doi.org/10.1038/srep35542.

[221]

Wang Y, He T, Liu J, Liu H, Zhou L, Hao W, et al. Synergistic effects of overexpression of BMP-2 and TGF-β3 on osteogenic differentiation of bone marrow mesenchymal stem cells. Mol Med Rep. 2016; 14: 5514-20. https://doi.org/10.3892/mmr.2016.5961.

[222]

Yan L, Wu X. Exosomes produced from 3D cultures of umbilical cord mesenchymal stem cells in a hollow-fiber bioreactor show improved osteochondral regeneration activity. Cell Biol Toxicol. 2020; 36: 165-78. https://doi.org/10.1007/s10565-019-09504-5.

[223]

Hakamivala A, Shuxin L, Robinson K, Huang Y, Yu S, Yuan B, et al. Recruitment of endogenous progenitor cells by erythropoietin loaded particles for in situ cartilage regeneration. Bioact Mater. 2020; 5: 142-52. https://doi.org/10.1016/j.bioactmat.2020.01.007.

[224]

Coryell PR, Diekman BO, Loeser RF. Mechanisms and therapeutic implications of cellular senescence in osteoarthritis. Nat Rev Rheumatol. 2021; 17: 47-57. https://doi.org/10.1038/s41584-020-00533-7.

[225]

Paez-Ribes M, González-Gualda E, Doherty GJ, Muñoz-Espín D. Targeting senescent cells in translational medicine. EMBO Mol Med. 2019; 11: e10234. https://doi.org/10.15252/emmm.201810234.

[226]

Tchkonia T, Zhu Y, van Deursen J, Campisi J, Kirkland JL. Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. J Clin Invest. 2013; 123: 966-72. https://doi.org/10.1172/JCI64098.

[227]

Choi SM, Lee KM, Ryu SB, Park YJ, Hwang YG, Baek D, et al. Enhanced articular cartilage regeneration with SIRT1-activated MSCs using gelatin-based hydrogel. Cell Death Dis. 2018; 9: 866. https://doi.org/10.1038/s41419-018-0914-1.

[228]

Xu L, Ma F, Huang J, Frankie Leung KL, Qin C, Lu WW, et al. Metformin hydrochloride encapsulation by alginate strontium hydrogel for cartilage regeneration by reliving cellular senescence. Biomacromolecules. 2021; 22: 671-80. https://doi.org/10.1021/acs.biomac.0c01488.

[229]

Zhu J, Yang S, Qi Y, Gong Z, Zhang H, Liang K, et al. Stem cell-homing hydrogel-based miR-29b-5p delivery promotes cartilage regeneration by suppressing senescence in an osteoarthritis rat model. Sci Adv. 2022; 8: eabk0011. https://doi.org/10.1126/sciadv.abk0011.

[230]

Jiang G, Li S, Yu K, He B, Hong J, Xu T, et al. A 3D-printed PRP-GelMA hydrogel promotes osteochondral regeneration through M2 macrophage polarization in a rabbit model. Acta Biomater. 2021; 128: 150-62. https://doi.org/10.1016/j.actbio.2021.04.010.

[231]

Yu H, Huang C, Kong X, Ma J, Ren P, Chen J, et al. Nanoarchitectonics of cartilage-targeting hydrogel microspheres with reactive oxygen species responsiveness for the repair of osteoarthritis. ACS Appl Mater Interfaces. 2022; 14: 40711-23. https://doi.org/10.1021/acsami.2c12703.

[232]

Xia X, Liu Y, Lu Y, Liu J, Deng Y, Wu Y, et al. Retuning mitochondrial apoptosis/mitophagy balance via SIRT3-energized and microenvironment-modulated hydrogel microspheres to impede osteoarthritis. Adv Healthc Mater. 2023; 12:e2302475. https://doi.org/10.1002/adhm.202302475.

[233]

Ye W, Yang Z, Cao F, Li H, Zhao T, Zhang H, et al. Articular cartilage reconstruction with TGF-β1-simulating self-assembling peptide hydrogel-based composite scaffold. Acta Biomater. 2022; 146: 94-106. https://doi.org/10.1016/j.actbio.2022.05.012.

[234]

Bordbar S, Li Z, Lotfibakhshaiesh N, Ai J, Tavassoli A, Beheshtizadeh N, et al. Cartilage tissue engineering using decellularized biomatrix hydrogel containing TGF-β-loaded alginate microspheres in mechanically loaded bioreactor. Sci Rep. 2024; 14: 11991. https://doi.org/10.1038/s41598-024-62474-5.

[235]

Thorpe SD, Buckley CT, Vinardell T, O’Brien FJ, Campbell VA, Kelly DJ. The response of bone marrow-derived mesenchymal stem cells to dynamic compression following TGF-beta3 induced chondrogenic differentiation. Ann Biomed Eng. 2010; 38: 2896-909. https://doi.org/10.1007/s10439-010-0059-6.

[236]

Lee CH, Cook JL, Mendelson A, Moioli EK, Yao H, Mao JJ. Regeneration of the articular surface of the rabbit synovial joint by cell homing: a proof of concept study. Lancet Lond Engl. 2010; 376: 440-8. https://doi.org/10.1016/S0140-6736(10)60668-X.

[237]

Wu SC, Chang JK, Wang CK, Wang GJ, Ho ML. Enhancement of chondrogenesis of human adipose derived stem cells in a hyaluronan-enriched microenvironment. Biomaterials. 2010; 31: 631-40. https://doi.org/10.1016/j.biomaterials.2009.09.089.

[238]

Deng ZH, Li YS, Gao X, Lei GH, Huard J. Bone morphogenetic proteins for articular cartilage regeneration. Osteoarthr Cartil. 2018; 26: 1153-61. https://doi.org/10.1016/j.joca.2018.03.007.

[239]

Jha AK, Yang W, Kirn-Safran CB, Farach-Carson MC, Jia X. Perlecan domain I-conjugated, hyaluronic acid-based hydrogel particles for enhanced chondrogenic differentiation via BMP-2 release. Biomaterials. 2009; 30: 6964-75. https://doi.org/10.1016/j.biomaterials.2009.09.009.

[240]

Reyes R, Delgado A, Sánchez E, Fernández A, Hernández A, Evora C. Repair of an osteochondral defect by sustained delivery of BMP-2 or TGFβ1 from a bilayered alginate-PLGA scaffold. J Tissue Eng Regen Med. 2014; 8: 521-33. https://doi.org/10.1002/term.1549.

[241]

Vayas R, Reyes R, Arnau MR, Évora C, Delgado A. Injectable scaffold for bone marrow stem cells and bone morphogenetic Protein-2 to repair cartilage. Cartilage. 2021; 12: 293-306. https://doi.org/10.1177/1947603519841682.

[242]

Sarsenova M, Raimagambetov Y, Issabekova A, Karzhauov M, Kudaibergen G, Akhmetkarimova Z, et al. Regeneration of osteochondral defects by combined delivery of synovium-derived mesenchymal stem cells, TGF-β1 and BMP-4 in heparin-conjugated fibrin hydrogel. Polymers. 2022; 14: 5343. https://doi.org/10.3390/polym14245343.

[243]

Ruan X, Jin X, Sun F, Pi J, Jinghu Y, Lin X, et al. IGF signaling pathway in bone and cartilage development, homeostasis, and disease. FASEB J Off Publ Fed Am Soc Exp Biol. 2024; 38:e70031. https://doi.org/10.1096/fj.202401298R.

[244]

Jiang X, Huang B, Yang H, Li G, Zhang C, Yang G, et al. TGF-β1 is involved in vitamin D-induced chondrogenic differentiation of bone marrow-derived mesenchymal stem cells by regulating the ERK/JNK pathway. Cell Physiol Biochem Int J Exp Cell Physiol Biochem Pharmacol. 2017; 42: 2230-41. https://doi.org/10.1159/000479997.

[245]

Robinson WH, Lepus CM, Wang Q, Raghu H, Mao R, Lindstrom TM, et al. Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis. Nat Rev Rheumatol. 2016; 12: 580-92. https://doi.org/10.1038/nrrheum.2016.136.

[246]

Evans CH, Ghivizzani SC, Robbins PD. Orthopaedic gene therapy: twenty-five years on. JBJS Rev. 2021; 9: 10.2106.

[247]

Sang X, Zhao X, Yan L, Jin X, Wang X, Wang J, et al. Thermosensitive hydrogel loaded with primary chondrocyte-derived exosomes promotes cartilage repair by regulating macrophage polarization in osteoarthritis. Tissue Eng Regen Med. 2022; 19: 629-42. https://doi.org/10.1007/s13770-022-00437-5.

[248]

Deng Z, Gao X, Sun X, Amra S, Lu A, Cui Y, et al. Characterization of articular cartilage homeostasis and the mechanism of superior cartilage regeneration of MRL/MpJ mice. FASEB J Off Publ Fed Am Soc Exp Biol. 2019; 33: 8809-21. https://doi.org/10.1096/fj.201802132RR.

[249]

Chen Y, Jiang W, Yong H, He M, Yang Y, Deng Z, et al. Macrophages in osteoarthritis: pathophysiology and therapeutics. Am J Transl Res. 2020; 12: 261-8.

[250]

Fernandes TL, Gomoll AH, Lattermann C, Hernandez AJ, Bueno DF, Amano MT. Macrophage: a potential target on cartilage regeneration. Front Immunol. 2020; 11: 111. https://doi.org/10.3389/fimmu.2020.00111.

[251]

Wu CL, Harasymowicz NS, Klimak MA, Collins KH, Guilak F. The role of macrophages in osteoarthritis and cartilage repair. Osteoarthr Cartil. 2020; 28: 544-54. https://doi.org/10.1016/j.joca.2019.12.007.

[252]

Ji X, Shao H, Li X, Ullah MW, Luo G, Xu Z, et al. Injectable immunomodulation-based porous chitosan microspheres/HPCH hydrogel composites as a controlled drug delivery system for osteochondral regeneration. Biomaterials. 2022; 285: 121530. https://doi.org/10.1016/j.biomaterials.2022.121530.

[253]

Peng L, Zhou Y, Lu W, Zhu W, Li Y, Chen K, et al. Characterization of a novel polyvinyl alcohol/chitosan porous hydrogel combined with bone marrow mesenchymal stem cells and its application in articular cartilage repair. BMC Musculoskelet Disord. 2019; 20: 257. https://doi.org/10.1186/s12891-019-2644-7.

[254]

Liu-Bryan R, Terkeltaub R. Emerging regulators of the inflammatory process in osteoarthritis. Nat Rev Rheumatol. 2015; 11: 35-44. https://doi.org/10.1038/nrrheum.2014.162.

[255]

Zheng L, Zhang Z, Sheng P, Mobasheri A. The role of metabolism in chondrocyte dysfunction and the progression of osteoarthritis. Ageing Res Rev. 2021; 66: 101249. https://doi.org/10.1016/j.arr.2020.101249.

[256]

Wang Q, Qi B, Shi S, Jiang W, Li D, Jiang X, et al. Melatonin alleviates osteoarthritis by regulating NADPH oxidase 4-induced ferroptosis and mitigating mitochondrial dysfunction. J Pineal Res. 2024; 76: e12992. https://doi.org/10.1111/jpi.12992.

[257]

Chiang MY, Cheng IY, Chou SH, Tsai JH, Chen YJ, Lu HE, et al. A smart injectable composite hydrogel with magnetic navigation and controlled glutathione release for promoting in situ chondrocyte array and self-healing in damaged cartilage tissue. J Mater Chem B. 2021; 9: 9370-82. https://doi.org/10.1039/D1TB02030G.

[258]

Green DR, Van Houten B. Mitochondrial quality control. Cell. 2011; 147: 950-950.e1. https://doi.org/10.1016/j.cell.2011.10.036.

[259]

Zhu Y, Ye L, Cai X, Li Z, Fan Y, Yang F. Icariin-loaded hydrogel regulates bone marrow mesenchymal stem cell chondrogenic differentiation and promotes cartilage repair in osteoarthritis. Front Bioeng Biotechnol. 2022; 10: 755260. https://doi.org/10.3389/fbioe.2022.755260.

[260]

Wang P, Xiong X, Zhang J, Qin S, Wang W, Liu Z. Icariin increases chondrocyte vitality by promoting hypoxia-inducible factor-1α expression and anaerobic glycolysis. Knee. 2020; 27: 18-25. https://doi.org/10.1016/j.knee.2019.09.012.

[261]

Yang X, Chen W, Zhao X, Chen L, Li W, Ran J, et al. Pyruvate kinase M2 modulates the glycolysis of chondrocyte and extracellular matrix in osteoarthritis. DNA Cell Biol. 2018; 37: 271-7. https://doi.org/10.1089/dna.2017.4048.

[262]

Patel JM, Saleh KS, Burdick JA, Mauck RL. Bioactive factors for cartilage repair and regeneration: improving delivery, retention, and activity. Acta Biomater. 2019; 93: 222-38. https://doi.org/10.1016/j.actbio.2019.01.061.

[263]

Sheehy EJ, Vinardell T, Buckley CT, Kelly DJ. Engineering osteochondral constructs through spatial regulation of endochondral ossification. Acta Biomater. 2013; 9: 5484-92. https://doi.org/10.1016/j.actbio.2012.11.008.

[264]

Atwal A, Dale TP, Snow M, Forsyth NR, Davoodi P. Injectable hydrogels: An emerging therapeutic strategy for cartilage regeneration. Adv Colloid Interf Sci. 2023; 321: 103030. https://doi.org/10.1016/j.cis.2023.103030.

[265]

Liu H, Cheng Y, Chen J, Chang F, Wang J, Ding J, et al. Component effect of stem cell-loaded thermosensitive polypeptide hydrogels on cartilage repair. Acta Biomater. 2018; 73: 103-11. https://doi.org/10.1016/j.actbio.2018.04.035.

[266]

Naghizadeh Z, Karkhaneh A, Nokhbatolfoghahaei H, Farzad-Mohajeri S, Rezai-Rad M, Dehghan MM, et al. Cartilage regeneration with dual-drug-releasing injectable hydrogel/microparticle system: In vitro and in vivo study. J Cell Physiol. 2021; 236: 2194-204. https://doi.org/10.1002/jcp.30006.

[267]

Shan BH, Wu FG. Hydrogel-based growth factor delivery platforms: strategies and recent advances. Adv Mater Deerfield Beach Fla. 2023; 36: e2210707. https://doi.org/10.1002/adma.202210707.

[268]

Zhang M, Hu W, Cai C, Wu Y, Li J, Dong S. Advanced application of stimuli-responsive drug delivery system for inflammatory arthritis treatment. Mater Today Bio. 2022; 14: 100223. https://doi.org/10.1016/j.mtbio.2022.100223.

[269]

Parmar PA, Skaalure SC, Chow LW, St-Pierre JP, Stoichevska V, Peng YY, et al. Temporally degradable collagen-mimetic hydrogels tuned to chondrogenesis of human mesenchymal stem cells. Biomaterials. 2016; 99: 56-71. https://doi.org/10.1016/j.biomaterials.2016.05.011.

[270]

Strehin I, Nahas Z, Arora K, Nguyen T, Elisseeff J. A versatile pH sensitive chondroitin sulfate-PEG tissue adhesive and hydrogel. Biomaterials. 2010; 31: 2788-97. https://doi.org/10.1016/j.biomaterials.2009.12.033.

[271]

Yuan X, Wan J, Yang Y, Huang L, Zhou C, Su J, et al. Thermosensitive hydrogel for cartilage regeneration via synergistic delivery of SDF-1α like polypeptides and kartogenin. Carbohydr Polym. 2023; 304: 120492. https://doi.org/10.1016/j.carbpol.2022.120492.

[272]

Li C, Armstrong JPK, Pence IJ, Kit-Anan W, Puetzer JL, Correia Carreira S, et al. Glycosylated superparamagnetic nanoparticle gradients for osteochondral tissue engineering. Biomaterials. 2018; 176: 24-33. https://doi.org/10.1016/j.biomaterials.2018.05.029.

[273]

Wu X, Li P, Cheng J, Xu Q, Lu B, Han C, et al. ROS-sensitive nanoparticles Co-delivering dexamethasone and CDMP-1 for the treatment of osteoarthritis through chondrogenic differentiation induction and inflammation inhibition. Front Bioeng Biotechnol. 2021; 9: 608150. https://doi.org/10.3389/fbioe.2021.608150.

[274]

Li J, Chen G, Xu X, Abdou P, Jiang Q, Shi D, et al. Advances of injectable hydrogel-based scaffolds for cartilage regeneration. Regen Biomater. 2019; 6: 129-40. https://doi.org/10.1093/rb/rbz022.

[275]

Singh YP, Moses JC, Bhardwaj N, Mandal BB. Injectable hydrogels: a new paradigm for osteochondral tissue engineering. J Mater Chem B. 2018; 6: 5499-529. https://doi.org/10.1039/C8TB01430B.

[276]

Olov N, Bagheri-Khoulenjani S, Mirzadeh H. Injectable hydrogels for bone and cartilage tissue engineering: a review. Prog Biomater. 2022; 11: 113-35. https://doi.org/10.1007/s40204-022-00185-8.

[277]

Rey-Rico A, Venkatesan JK, Frisch J, Rial-Hermida I, Schmitt G, Concheiro A, et al. PEO-PPO-PEO micelles as effective rAAV-mediated gene delivery systems to target human mesenchymal stem cells without altering their differentiation potency. Acta Biomater. 2015; 27: 42-52. https://doi.org/10.1016/j.actbio.2015.08.046.

[278]

Russo E, Villa C. Poloxamer hydrogels for biomedical applications. Pharmaceutics. 2019; 11: 671. https://doi.org/10.3390/pharmaceutics11120671.

[279]

Rizzo F, Kehr NS. Recent advances in injectable hydrogels for controlled and local drug delivery. Adv Healthc Mater. 2021; 10: e2001341. https://doi.org/10.1002/adhm.202001341.

[280]

Vinikoor T, Dzidotor GK, Le TT, Liu Y, Kan HM, Barui S, et al. Injectable and biodegradable piezoelectric hydrogel for osteoarthritis treatment. Nat Commun. 2023; 14: 6257. https://doi.org/10.1038/s41467-023-41594-y.

[281]

Bhogoju S, Khan S, Subramanian A. Continuous low-intensity ultrasound preserves chondrogenesis of mesenchymal stromal cells in the presence of cytokines by inhibiting NFκB activation. Biomolecules. 2022; 12: 434. https://doi.org/10.3390/biom12030434.

[282]

Chandan R, Mehta S, Banerjee R. Ultrasound-responsive carriers for therapeutic applications. ACS Biomater Sci Eng. 2020; 6: 4731-47. https://doi.org/10.1021/acsbiomaterials.9b01979.

[283]

Parate D, Kadir ND, Celik C, Lee EH, Hui JHP, Franco-Obregón A, et al. Pulsed electromagnetic fields potentiate the paracrine function of mesenchymal stem cells for cartilage regeneration. Stem Cell Res Ther. 2020; 11: 46. https://doi.org/10.1186/s13287-020-1566-5.

[284]

Zhang N, Lock J, Sallee A, Liu H. Magnetic nanocomposite hydrogel for potential cartilage tissue engineering: synthesis, characterization, and cytocompatibility with bone marrow derived mesenchymal stem cells. ACS Appl Mater Interfaces. 2015; 7: 20987-98. https://doi.org/10.1021/acsami.5b06939.

[285]

Wu Y, Zou J, Tang K, Xia Y, Wang X, Song L, et al. From electricity to vitality: the emerging use of piezoelectric materials in tissue regeneration. Burns Trauma. 2024; 12: tkae013. https://doi.org/10.1093/burnst/tkae013.

[286]

Karimi M, Sahandi Zangabad P, Baghaee-Ravari S, Ghazadeh M, Mirshekari H, Hamblin MR. Smart nanostructures for cargo delivery: uncaging and activating by light. J Am Chem Soc. 2017; 139: 4584-610. https://doi.org/10.1021/jacs.6b08313.

[287]

Hua Y, Xia H, Jia L, Zhao J, Zhao D, Yan X, et al. Ultrafast, tough, and adhesive hydrogel based on hybrid photocrosslinking for articular cartilage repair in water-filled arthroscopy. Sci Adv. 2021; 7:eabg0628. https://doi.org/10.1126/sciadv.abg0628.

[288]

Sharma B, Fermanian S, Gibson M, Unterman S, Herzka DA, Cascio B, et al. Human cartilage repair with a photoreactive adhesive-hydrogel composite. Sci Transl Med. 2013; 5: 167ra6. https://doi.org/10.1126/scitranslmed.3004838.

[289]

Zhang FX, Liu P, Ding W, Meng QB, Su DH, Zhang QC, et al. Injectable mussel-inspired highly adhesive hydrogel with exosomes for endogenous cell recruitment and cartilage defect regeneration. Biomaterials. 2021; 278: 121169. https://doi.org/10.1016/j.biomaterials.2021.121169.

[290]

Karami P, Laurent A, Philippe V, Applegate LA, Pioletti DP, Martin R. Cartilage repair: promise of adhesive Orthopedic hydrogels. Int J Mol Sci. 2024; 25: 9984. https://doi.org/10.3390/ijms25189984.

[291]

Awasthi S, Gaur JK, Pandey SK, Bobji MS, Srivastava C. High-strength, strongly bonded nanocomposite hydrogels for cartilage repair. ACS Appl Mater Interfaces. 2021; 13: 24505-23. https://doi.org/10.1021/acsami.1c05394.

[292]

Fang J, Liao J, Zhong C, Lu X, Ren F. High-strength, biomimetic functional chitosan-based hydrogels for full-thickness osteochondral defect repair. ACS Biomater Sci Eng. 2022; 8: 4449-61. https://doi.org/10.1021/acsbiomaterials.2c00187.

[293]

Costa AMS, Mano JF. Extremely strong and tough hydrogels as prospective candidates for tissue repair-a review. Eur Polym J. 2015; 72: 344-64. https://doi.org/10.1016/j.eurpolymj.2015.07.053.

[294]

Dai W, Sun M, Leng X, Hu X, Ao Y. Recent progress in 3D printing of elastic and high-strength hydrogels for the treatment of osteochondral and cartilage diseases. Front Bioeng Biotechnol. 2020; 8: 604814. https://doi.org/10.3389/fbioe.2020.604814.

[295]

Cui P, Pan P, Qin L, Wang X, Chen X, Deng Y, et al. Nanoengineered hydrogels as 3D biomimetic extracellular matrix with injectable and sustained delivery capability for cartilage regeneration. Bioact Mater. 2023; 19: 487-98. https://doi.org/10.1016/j.bioactmat.2022.03.032.

[296]

Lin J, Jia S, Cao F, Huang J, Chen J, Wang J, et al. Research progress on injectable microspheres as new strategies for the treatment of osteoarthritis through promotion of cartilage repair. Adv Funct Mater. 2024; 34: 2400585. https://doi.org/10.1002/adfm.202400585.

[297]

Censi R, Dubbini A, Matricardi P. Bioactive hydrogel scaffolds-advances in cartilage regeneration through controlled drug delivery. Curr Pharm Des. 2015; 21: 1545-55. https://doi.org/10.2174/1381612821666150115150712.

[298]

Zhou L, Jiao X, Liu S, Hao M, Cheng S, Zhang P, et al. Functional DNA-based hydrogel intelligent materials for biomedical applications. J Mater Chem B. 2020; 8: 1991-2009. https://doi.org/10.1039/C9TB02716E.

[299]

Gu Z, Wang J, Fu Y, Pan H, He H, Gan Q, et al. Smart biomaterials for articular cartilage repair and regeneration. Adv Funct Mater. 2023; 33: 2212561. https://doi.org/10.1002/adfm.202212561.

[300]

Mandal A, Clegg JR, Anselmo AC, Mitragotri S. Hydrogels in the clinic. Bioeng Transl Med. 2020; 5: e10158. https://doi.org/10.1002/btm2.10158.

[301]

Cascone S, Lamberti G. Hydrogel-based commercial products for biomedical applications: a review. Int J Pharm. 2020; 573: 118803. https://doi.org/10.1016/j.ijpharm.2019.118803.

[302]

Zhu H, Liu F, Zhai X, Tong Z, Li H, Dong W, et al. Revisiting matrix hydrogel composed of gelatin and hyaluronic acid and its application in cartilage regeneration. Biochem Biophys Res Commun. 2023; 681: 97-105. https://doi.org/10.1016/j.bbrc.2023.09.060.

[303]

Liang W, Yang R, Qin L, Liang T, Chen W. Current status and perspectives of research on polymer hydrogels in the treatment and protection of osteoarthritis. Macromol Biosci. 2025; e2500016. https://doi.org/10.1002/mabi.202500016.

[304]

VitroGel® RGD hydrogel for 3D cell culture. Cambridge, MA: TheWell Bioscience [Internet], 2023, [cited 2023 Nov 16]. Available from: https://www.thewellbio.com/product/vitrogel-rgd/.

[305]

Wang F, Nan L, Zhou S, Liu Y, Wang Z, Wang J, et al. Injectable hydrogel combined with nucleus pulposus-derived mesenchymal stem cells for the treatment of degenerative intervertebral disc in rats. Stem Cells Int. 2019; 2019: e8496025.

[306]

Li Z, Cao B, Wang X, Ye K, Li S, Ding J. Effects of RGD nanospacing on chondrogenic differentiation of mesenchymal stem cells. J Mater Chem B. 2015; 3: 5197-209. https://doi.org/10.1039/C5TB00455A.

[307]

EUFLEXXA [Internet]. Malvern, PA: Ferring Pharmaceuticals, 2023. [cited 2023 Nov 28]. Available from: https://www.euflexxa.com/.

[308]

Altman RD, Rosen JE, Bloch DA, Hatoum HT, Korner P. A double-blind, randomized, saline-controlled study of the efficacy and safety of EUFLEXXA for treatment of painful osteoarthritis of the knee, with an open-label safety extension (the FLEXX trial). Semin Arthritis Rheum. 2009; 39: 1-9. https://doi.org/10.1016/j.semarthrit.2009.04.001.

[309]

Webner D, Huang Y, Hummer CD. Intraarticular hyaluronic acid preparations for knee osteoarthritis: are some better than others? Cartilage. 2021; 13: 1619S-36. https://doi.org/10.1177/19476035211017320.

[310]

Euflexxa Side Effects: Common, Severe, Long Term [Internet]. Austin, TX: Drugs.com. [cited 2025 Jan 27]. Available from: https://www.drugs.com/sfx/euflexxa-side-effects.html.

[311]

Munns J, Park DK, Singh K. Role of osteogenic protein-1/bone morphogenetic protein-7 in spinal fusion. Orthop Res Rev. 2009; 1: 11-21.

[312]

Catros S, Molenberg A, Freilich M, Dard M. Evaluation of a polyethylene glycol-osteogenic Protein-1 system on alveolar bone regeneration in the mini-pig. J Oral Implantol. 2015; 41: e96-101. https://doi.org/10.1563/AAID-JOI-D-13-00307.

[313]

Sampath TK, Maliakal JC, Hauschka PV, Jones WK, Sasak H, Tucker RF, et al. Recombinant human osteogenic protein-1 (hOP-1) induces new bone formation in vivo with a specific activity comparable with natural bovine osteogenic protein and stimulates osteoblast proliferation and differentiation in vitro. J Biol Chem. 1992; 267: 20352-62. https://doi.org/10.1016/S0021-9258(19)88709-4.

[314]

Nishida Y, Knudson CB, Kuettner KE, Knudson W. Osteogenic protein-1 promotes the synthesis and retention of extracellular matrix within bovine articular cartilage and chondrocyte cultures. Osteoarthr Cartil. 2000; 8: 127-36. https://doi.org/10.1053/joca.1999.0281.

[315]

Menaa F. Hyaluronic acid and derivatives for tissue engineering. J Biotechnol Biomater. 2013; s3: 001. https://doi.org/10.4172/2155-952X.S3-001.

[316]

Pavesio A, Abatangelo G, Borrione A, Brocchetta D, Hollander AP, Kon E, et al. Hyaluronan-based scaffolds (Hyalograft C) in the treatment of knee cartilage defects: preliminary clinical findings. Novartis Found Symp. 2003; 249: 203-17, discussion 229-233, 234-8, 239-41. https://doi.org/10.1002/0470867973.ch15.

[317]

Riccio M, Battiston B, Pajardi G, Corradi M, Passaretti U, Atzei A, et al. Efficiency of Hyaloglide® in the prevention of the recurrence of adhesions after tenolysis of flexor tendons in zone II: a randomized, controlled, multicentre clinical trial. J Hand Surg Eur. 2010; 35: 130-8. https://doi.org/10.1177/1753193409342044.

[318]

Chiang H, Liao CJ, Wang YH, Huang HY, Chen CN, Hsieh CH, et al. Comparison of articular cartilage repair by autologous chondrocytes with and without in vitro cultivation. Tissue Eng Part C Methods. 2010; 16: 291-300. https://doi.org/10.1089/ten.tec.2009.0298.

[319]

Gel-One® Cross-linked Hyaluronate [Internet]. Warsaw, IN: Zimmer Biomet, 2023 [cited 2023 Nov 28]. Available from: https://www.zimmerbiomet.com/en/products-and-solutions/products/restorative-therapies/gel-one.html.

[320]

Ishikawa M, Yoshioka K, Urano K, Tanaka Y, Hatanaka T, Nii A. Biocompatibility of cross-linked hyaluronate (Gel-200) for the treatment of knee osteoarthritis. Osteoarthr Cartil. 2014; 22: 1902-9. https://doi.org/10.1016/j.joca.2014.08.002.

[321]

Peck J, Slovek A, Miro P, Vij N, Traube B, Lee C, et al. A comprehensive review of Viscosupplementation in osteoarthritis of the knee. Orthop Rev. 2021; 13: 25549. https://doi.org/10.52965/001c.25549.

[322]

Jeyachandran D, Murshed M, Haglund L, Cerruti M. A bioglass-poly(lactic-co-glycolic acid) scaffold@fibrin hydrogel construct to support endochondral bone formation. Adv Healthc Mater. 2023; 12: e2300211. https://doi.org/10.1002/adhm.202300211.

PDF (3460KB)

0

Accesses

0

Citation

Detail

Sections
Recommended

/

〈 〉