514
Views
5
CrossRef citations to date
0
Altmetric
REVIEW

Current and Novel Therapeutics for Articular Cartilage Repair and Regeneration

, , &
Pages 485-502 | Received 27 Feb 2023, Accepted 28 May 2023, Published online: 20 Jun 2023

References

  • Sophia Fox AJ, Bedi A, Rodeo SA. The basic science of articular cartilage: structure, composition, and function. Sports Health. 2009;1(6):461–468. doi:10.1177/1941738109350438
  • Chiang H, Jiang CC. Repair of articular cartilage defects: review and perspectives. J Formos Med Assoc. 2009;108(2):87–101. doi:10.1016/s0929-6646(09)60039-5
  • Borrelli J, Olson SA, Godbout C, Schemitsch EH, Stannard JP, Giannoudis PV. Understanding articular cartilage injury and potential treatments. J Orthop Trauma. 2019;33(Suppl 6):S6–s12. doi:10.1097/bot.0000000000001472
  • Chubinskaya S, Haudenschild D, Gasser S, Stannard J, Krettek C, Borrelli J. Articular cartilage injury and potential remedies. J Orthop Trauma. 2015;29(Suppl 12):S47–S52. doi:10.1097/bot.0000000000000462
  • Wilder FV, Hall BJ, Barrett JP, Lemrow NB. History of acute knee injury and osteoarthritis of the knee: a prospective epidemiological assessment. The Clearwater Osteoarthritis Study. Osteoarthritis Cartilage. 2002;10(8):611–616. doi:10.1053/joca.2002.0795
  • Liu Y, Shah KM, Luo J. Strategies for articular cartilage repair and regeneration. Front Bioeng Biotechnol. 2021;9:770655. doi:10.3389/fbioe.2021.770655
  • Solanki K, Shanmugasundaram S, Shetty N, Kim S-J. Articular cartilage repair & joint preservation: a review of the current status of biological approach. J Clin Orthopaed Trauma. 2021;22:101602. doi:10.1016/j.jcot.2021.101602
  • Roseti L, Grigolo B. Current concepts and perspectives for articular cartilage regeneration. J Exp Orthop. 2022;9(1):61. doi:10.1186/s40634-022-00498-4
  • Jiang S, Tian G, Li X, et al. Research progress on stem cell therapies for articular cartilage regeneration. Stem Cells Int. 2021;2021:8882505. doi:10.1155/2021/8882505
  • Steadman JR, Rodkey WG, Rodrigo JJ. Microfracture: surgical technique and rehabilitation to treat chondral defects. Clin Orthop Relat Res. 2001;391:S362–9. doi:10.1097/00003086-200110001-00033
  • Steadman JR, Rodkey WG, Briggs KK. Microfracture: its history and experience of the developing surgeon. Cartilage. 2010;1(2):78–86. doi:10.1177/1947603510365533
  • Erggelet C, Vavken P. Microfracture for the treatment of cartilage defects in the knee joint - A golden standard? J Clin Orthop Trauma. 2016;7(3):145–152. doi:10.1016/j.jcot.2016.06.015
  • Negrin L, Kutscha-Lissberg F, Gartlehner G, Vecsei V. Clinical outcome after microfracture of the knee: a meta-analysis of before/after-data of controlled studies. Int Orthop. 2012;36(1):43–50. doi:10.1007/s00264-011-1364-x
  • Fortier LM, Knapik DM, Dasari SP, et al. Clinical and magnetic resonance imaging outcomes after microfracture treatment with and without augmentation for focal chondral lesions in the knee: a systematic review and meta-analysis. Am J Sports Med. 2022;3635465221087365. doi:10.1177/03635465221087365
  • Goyal D, Keyhani S, Lee EH, Hui JH. Evidence-based status of microfracture technique: a systematic review of level I and II studies. Arthroscopy. 2013;29(9):1579–1588. doi:10.1016/j.arthro.2013.05.027
  • Mithoefer K, McAdams T, Williams RJ, Kreuz PC, Mandelbaum BR. Clinical efficacy of the microfracture technique for articular cartilage repair in the knee: an evidence-based systematic analysis. Am J Sports Med. 2009;37(10):2053–2063. doi:10.1177/0363546508328414
  • Kreuz PC, Steinwachs MR, Erggelet C, et al. Results after microfracture of full-thickness chondral defects in different compartments in the knee. Osteoarthritis Cartilage. 2006;14(11):1119–1125. doi:10.1016/j.joca.2006.05.003
  • Bae DK, Yoon KH, Song SJ. Cartilage healing after microfracture in osteoarthritic knees. Arthroscopy. 2006;22(4):367–374. doi:10.1016/j.arthro.2006.01.015
  • Riedl M, Rupp M, Walter N, et al. Practical relevance of institutional guidelines in translational large animal studies of cartilage repair-a multidisciplinary survey. Medicina. 2022;58(12):254.
  • Gao L, Goebel LKH, Orth P, Cucchiarini M, Madry H. Subchondral drilling for articular cartilage repair: a systematic review of translational research. Dis Model Mech. 2018;11(6):124.
  • Chen H, Sun J, Hoemann CD, et al. Drilling and microfracture lead to different bone structure and necrosis during bone-marrow stimulation for cartilage repair. J Orthop Res. 2009;27(11):1432–1438. doi:10.1002/jor.20905
  • Ozmeriç A, Alemdaroğlu KB, Aydoğan NH. Treatment for cartilage injuries of the knee with a new treatment algorithm. World J Orthop. 2014;5(5):677–684. doi:10.5312/wjo.v5.i5.677
  • Choi JI, Lee KB. Comparison of clinical outcomes between arthroscopic subchondral drilling and microfracture for osteochondral lesions of the talus. Knee Surg Sports Traumatol Arthrosc. 2016;24(7):2140–2147. doi:10.1007/s00167-015-3511-1
  • LaPrade RF, Botker JC. Donor-site morbidity after osteochondral autograft transfer procedures. Arthroscopy. 2004;20(7):e69–73. doi:10.1016/j.arthro.2004.06.022
  • Rowland R, Colello M, Wyland DJ. Osteochondral autograft transfer procedure: arthroscopic technique and technical pearls. Arthrosc Tech. 2019;8(7):e713–e719. doi:10.1016/j.eats.2019.03.006
  • Cook JL, Stoker AM, Stannard JP, et al. A novel system improves preservation of osteochondral allografts. Clin Orthop Relat Res. 2014;472(11):3404–3414. doi:10.1007/s11999-014-3773-9
  • Richter DL, Schenck RC, Wascher DC, Treme G. Knee articular cartilage repair and restoration techniques: a review of the literature. Sports Health. 2016;8(2):153–160. doi:10.1177/1941738115611350
  • Welch T, Mandelbaum B, Tom M. Autologous chondrocyte implantation: past, present, and future. Sports Med Arthrosc Rev. 2016;24(2):85–91. doi:10.1097/jsa.0000000000000115
  • Mistry H, Connock M, Pink J, et al. Autologous chondrocyte implantation in the knee: systematic review and economic evaluation. Health Technol Assess. 2017;21(6):1–294. doi:10.3310/hta21060
  • 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(3):156–163. doi:10.1302/2058-5241.5.190031
  • Brittberg M. Autologous chondrocyte implantation--technique and long-term follow-up. Injury. 2008;39(Suppl 1):S40–S49. doi:10.1016/j.injury.2008.01.040
  • Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med. 1994;331(14):889–895. doi:10.1056/nejm199410063311401
  • Bentley G, Greer RB. Homotransplantation of isolated epiphyseal and articular cartilage chondrocytes into joint surfaces of rabbits. Nature. 1971;230(5293):385–388. doi:10.1038/230385a0
  • Reverte-Vinaixa MM, Joshi N, Diaz-Ferreiro EW, Teixidor-Serra J, Dominguez-Oronoz R. Medium-term outcome of mosaicplasty for grade III-IV cartilage defects of the knee. J Orthop Surg. 2013;21(1):4–9. doi:10.1177/230949901302100104
  • Inderhaug E, Solheim E. Osteochondral autograft transplant (mosaicplasty) for knee articular cartilage defects. JBJS Essent Surg Tech. 2019;9(4):e34. doi:10.2106/JBJS.ST.18.00113
  • Park YB, Ha CW, Rhim JH, Lee HJ. Stem cell therapy for articular cartilage repair: review of the entity of cell populations used and the result of the clinical application of each entity. Am J Sports Med. 2018;46(10):2540–2552. doi:10.1177/0363546517729152
  • Olmsted-Davis EA, Gugala Z, Camargo F, et al. Primitive adult hematopoietic stem cells can function as osteoblast precursors. Proc Natl Acad Sci U S A. 2003;100(26):15877–15882. doi:10.1073/pnas.2632959100
  • Kacena MA, Gundberg CM, Horowitz MC. A reciprocal regulatory interaction between megakaryocytes, bone cells, and hematopoietic stem cells. Bone. 2006;39(5):978–984. doi:10.1016/j.bone.2006.05.019
  • Dominici M, Pritchard C, Garlits JE, Hofmann TJ, Persons DA, Horwitz EM. Hematopoietic cells and osteoblasts are derived from a common marrow progenitor after bone marrow transplantation. Proc Natl Acad Sci U S A. 2004;101(32):11761–11766. doi:10.1073/pnas.0404626101
  • Zaffagnini M, Boffa A, Andriolo L, Raggi F, Zaffagnini S, Filardo G. Orthobiologic injections for the treatment of hip osteoarthritis: a systematic review. J Clin Med. 2022;11(22):6663. doi:10.3390/jcm11226663
  • Cavallo C, Boffa A, de Girolamo L, et al. Bone marrow aspirate concentrate quality is affected by age and harvest site. Knee Surg Sports Traumatol Arthrosc. 2022. doi:10.1007/s00167-022-07153-6
  • Park YB, Ha CW, Lee CH, Yoon YC, Park YG. Cartilage regeneration in osteoarthritic patients by a composite of allogeneic umbilical cord blood-derived mesenchymal stem cells and hyaluronate hydrogel: results from a clinical trial for safety and proof-of-concept with 7 years of extended follow-up. Stem Cells Transl Med. 2017;6(2):613–621. doi:10.5966/sctm.2016-0157
  • Yamasaki S, Mera H, Itokazu M, Hashimoto Y, Wakitani S. Cartilage repair with autologous bone marrow mesenchymal stem cell transplantation: review of preclinical and clinical studies. Cartilage. 2014;5(4):196–202. doi:10.1177/1947603514534681
  • Teo AQA, Wong KL, Shen L, et al. Equivalent 10-year outcomes after implantation of autologous bone marrow–derived mesenchymal stem cells versus autologous chondrocyte implantation for chondral defects of the knee. Am J Sports Med. 2019;47(12):2881–2887. doi:10.1177/0363546519867933
  • Nejadnik H, Hui JH, Feng Choong EP, Tai BC, Lee EH. Autologous bone marrow-derived mesenchymal stem cells versus autologous chondrocyte implantation: an observational cohort study. Am J Sports Med. 2010;38(6):1110–1116. doi:10.1177/0363546509359067
  • Chahla J, Piuzzi NS, Mitchell JJ, et al. Intra-articular cellular therapy for osteoarthritis and focal cartilage defects of the knee: a systematic review of the literature and study quality analysis. J Bone Joint Surg Am. 2016;98(18):1511–1521. doi:10.2106/jbjs.15.01495
  • Houghton J, Stoicov C, Nomura S, et al. Gastric cancer originating from bone marrow-derived cells. Science. 2004;306(5701):1568–1571. doi:10.1126/science.1099513
  • Røsland GV, Svendsen A, Torsvik A, et al. Long-term cultures of bone marrow-derived human mesenchymal stem cells frequently undergo spontaneous malignant transformation. Cancer Res. 2009;69(13):5331–5339. doi:10.1158/0008-5472.Can-08-4630
  • Torsvik A, Røsland GV, Svendsen A, et al. Spontaneous malignant transformation of human mesenchymal stem cells reflects cross-contamination: putting the research field on track - letter. Cancer Res. 2010;70(15):6393–6396. doi:10.1158/0008-5472.Can-10-1305
  • Casiraghi F, Remuzzi G, Abbate M, Perico N. Multipotent mesenchymal stromal cell therapy and risk of malignancies. Stem Cell Rev Rep. 2013;9(1):65–79. doi:10.1007/s12015-011-9345-4
  • Peeters CM, Leijs MJ, Reijman M, van Osch GJ, Bos PK. Safety of intra-articular cell-therapy with culture-expanded stem cells in humans: a systematic literature review. Osteoarthritis Cartilage. 2013;21(10):1465–1473. doi:10.1016/j.joca.2013.06.025
  • Wakitani S, Okabe T, Horibe S, et al. Safety of autologous bone marrow-derived mesenchymal stem cell transplantation for cartilage repair in 41 patients with 45 joints followed for up to 11 years and 5 months. J Tissue Eng Regen Med. 2011;5(2):146–150. doi:10.1002/term.299
  • Reissis D, Tang QO, Cooper NC, et al. Current clinical evidence for the use of mesenchymal stem cells in articular cartilage repair. Expert Opin Biol Ther. 2016;16(4):535–557. doi:10.1517/14712598.2016.1145651
  • Filardo G, Perdisa F, Roffi A, Marcacci M, Kon E. Stem cells in articular cartilage regeneration. J Orthop Surg Res. 2016;11:42. doi:10.1186/s13018-016-0378-x
  • Bourin P, Bunnell BA, Casteilla L, et al. Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT). Cytotherapy. 2013;15(6):641–648. doi:10.1016/j.jcyt.2013.02.006
  • Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8(4):315–317. doi:10.1080/14653240600855905
  • Hass R, Kasper C, Böhm S, Jacobs R. Different populations and sources of human mesenchymal stem cells (MSC): a comparison of adult and neonatal tissue-derived MSC. Cell Commun Signal. 2011;9(1):1–14. doi:10.1186/1478-811X-9-12
  • Vinardell T, Thorpe SD, Buckley CT, Kelly DJ. Chondrogenesis and integration of mesenchymal stem cells within an in vitro cartilage defect repair model. Ann Biomed Eng. 2009;37(12):2556–2565. doi:10.1007/s10439-009-9791-1
  • de Vries–van Melle ML, Narcisi R, Kops N, et al. Chondrogenesis of mesenchymal stem cells in an osteochondral environment is mediated by the subchondral bone. Tissue Eng Part A. 2014;20(1–2):23–33. doi:10.1089/ten.tea.2013.0080
  • 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):1–19. doi:10.1186/s13075-014-0432-1
  • To K, Zhang B, Romain K, Mak C, Khan W. Synovium-derived mesenchymal stem cell transplantation in cartilage regeneration: a PRISMA review of in vivo studies. Front Bioengine Biotechnol. 2019;7:314. doi:10.3389/fbioe.2019.00314
  • Pak J. Regeneration of human bones in Hip osteonecrosis and human cartilage in knee osteoarthritis with autologous adipose-tissue-derived stem cells: a case series. J Med Case Rep. 2011;5:296. doi:10.1186/1752-1947-5-296
  • Meng HY, Lu V, Khan W. Adipose tissue-derived mesenchymal stem cells as a potential restorative treatment for cartilage defects: a PRISMA review and meta-analysis. Pharmaceuticals. 2021;14(12):1280. doi:10.3390/ph14121280
  • Koh Y-G, Kwon O-R, Kim Y-S, Choi Y-J, Tak D-H. Adipose-derived mesenchymal stem cells with microfracture versus microfracture alone: 2-year follow-up of a prospective randomized trial. Arthroscopy. 2016;32(1):97–109. doi:10.1016/j.arthro.2015.09.010
  • Freitag J, Wickham J, Shah K, Li D, Norsworthy C, Tenen A. Mesenchymal stem cell therapy combined with arthroscopic abrasion arthroplasty regenerates cartilage in patients with severe knee osteoarthritis: a case series. Regen Med. 2020;15(8):1957–1977. doi:10.2217/rme-2020-0128
  • Freitag J, Shah K, Wickham J, Li D, Norsworthy C, Tenen A. Evaluation of autologous adipose-derived mesenchymal stem cell therapy in focal chondral defects of the knee: a pilot case series. Regen Med. 2020;15(6):1703–1717. doi:10.2217/rme-2020-0027
  • Jo CH, Chai JW, Jeong EC, et al. Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a 2-year follow-up study. Am J Sports Med. 2017;45(12):2774–2783. doi:10.1177/0363546517716641
  • Castro-Viñuelas R, Sanjurjo-Rodríguez C, Piñeiro-Ramil M, et al. Induced pluripotent stem cells for cartilage repair: current status and future perspectives. Eur Cell Mater. 2018;36:96–109. doi:10.22203/eCM.v036a08
  • Steinert AF, Nöth U, Tuan RS. Concepts in gene therapy for cartilage repair. Injury. 2008;39(Suppl 1):S97–113. doi:10.1016/j.injury.2008.01.034
  • Sun Y, Huo C, Qiao Z, et al. Comparative proteomic analysis of exosomes and microvesicles in human saliva for lung cancer. J Proteome Res. 2018;17(3):1101–1107. doi:10.1021/acs.jproteome.7b00770
  • Li S, Li Y, Chen B, et al. exoRBase: a database of circRNA, lncRNA and mRNA in human blood exosomes. Nucleic Acids Res. 2017;46(D1):D106–D112. doi:10.1093/nar/gkx891
  • Cho S, Yang HC, Rhee WJ. Development and comparative analysis of human urine exosome isolation strategies. Process Biochem. 2020;88:197–203. doi:10.1016/j.procbio.2019.09.017
  • Vaswani K, Mitchell MD, Holland OJ, et al. A method for the isolation of exosomes from human and bovine milk. J Nutr Metab. 2019;2019:5764740. doi:10.1155/2019/5764740
  • Zhang Y, Liu Y, Liu H, Tang WH. Exosomes: biogenesis, biologic function and clinical potential. Cell Biosci. 2019;9(1):19. doi:10.1186/s13578-019-0282-2
  • Sun H, Hu S, Zhang Z, Lun J, Liao W, Zhang Z. Expression of exosomal microRNAs during chondrogenic differentiation of human bone mesenchymal stem cells. J Cell Biochem. 2019;120(1):171–181. doi:10.1002/jcb.27289
  • Vonk LA, van Dooremalen SFJ, Liv N, et al. Mesenchymal stromal/stem cell-derived extracellular vesicles promote human cartilage regeneration in vitro. Theranostics. 2018;8(4):906–920. doi:10.7150/thno.20746
  • Kim YG, Park U, Park BJ, Kim K. Exosome-mediated bidirectional signaling between mesenchymal stem cells and chondrocytes for enhanced chondrogenesis. Biotechnol Bioprocess Engine. 2019;24(5):734–744. doi:10.1007/s12257-019-0332-y
  • Woo CH, Kim HK, Jung GY, et al. Small extracellular vesicles from human adipose-derived stem cells attenuate cartilage degeneration. J Extracell Vesicles. 2020;9(1):1735249. doi:10.1080/20013078.2020.1735249
  • Harting MT, Srivastava AK, Zhaorigetu S, et al. Inflammation-stimulated mesenchymal stromal cell-derived extracellular vesicles attenuate inflammation. Stem Cells. 2018;36(1):79–90. doi:10.1002/stem.2730
  • Abraham A, Krasnodembskaya A. Mesenchymal stem cell-derived extracellular vesicles for the treatment of acute respiratory distress syndrome. Stem Cells Transl Med. 2020;9(1):28–38. doi:10.1002/sctm.19-0205
  • Zhang S, Teo KYW, Chuah SJ, Lai RC, Lim SK, Toh WS. MSC exosomes alleviate temporomandibular joint osteoarthritis by attenuating inflammation and restoring matrix homeostasis. Biomaterials. 2019;200:35–47. doi:10.1016/j.biomaterials.2019.02.006
  • Zhang J, Zhang J, Zhang Y, et al. Mesenchymal stem cells-derived exosomes ameliorate intervertebral disc degeneration through inhibiting pyroptosis. J Cell Mol Med. 2020;24(20):11742–11754. doi:10.1111/jcmm.15784
  • Yang W, Yu XH, Wang C, et al. Interleukin-1β in intervertebral disk degeneration. Clin Chim Acta. 2015;450:262–272. doi:10.1016/j.cca.2015.08.029
  • Xia C, Zeng Z, Fang B, et al. Mesenchymal stem cell-derived exosomes ameliorate intervertebral disc degeneration via anti-oxidant and anti-inflammatory effects. Free Radic Biol Med. 2019;143:1–15. doi:10.1016/j.freeradbiomed.2019.07.026
  • Fernandes TL, Gomoll AH, Lattermann C, Hernandez AJ, Bueno DF, Amano MT. Macrophage: a potential target on cartilage regeneration. Front Immunol. 2020;11:111. doi:10.3389/fimmu.2020.00111
  • Zhang J, Rong Y, Luo C, Cui W. Bone marrow mesenchymal stem cell-derived exosomes prevent osteoarthritis by regulating synovial macrophage polarization. Aging. 2020;12(24):25138–25152. doi:10.18632/aging.104110
  • He L, He T, Xing J, et al. Bone marrow mesenchymal stem cell-derived exosomes protect cartilage damage and relieve knee osteoarthritis pain in a rat model of osteoarthritis. Stem Cell Res Ther. 2020;11(1):276. doi:10.1186/s13287-020-01781-w
  • Lu K, Li HY, Yang K, et al. Exosomes as potential alternatives to stem cell therapy for intervertebral disc degeneration: in-vitro study on exosomes in interaction of nucleus pulposus cells and bone marrow mesenchymal stem cells. Stem Cell Res Ther. 2017;8(1):108. doi:10.1186/s13287-017-0563-9
  • Lan WR, Pan S, Li HY, et al. Inhibition of the Notch1 pathway promotes the effects of nucleus pulposus cell-derived exosomes on the differentiation of mesenchymal stem cells into nucleus pulposus-like cells in rats. Stem Cells Int. 2019;2019:8404168. doi:10.1155/2019/8404168
  • Li Z, Wang Y, Xiang S, et al. Chondrocytes-derived exosomal miR-8485 regulated the Wnt/β-catenin pathways to promote chondrogenic differentiation of BMSCs. Biochem Biophys Res Commun. 2020;523(2):506–513. doi:10.1016/j.bbrc.2019.12.065
  • Rong Y, Zhang J, Jiang D, et al. Hypoxic pretreatment of small extracellular vesicles mediates cartilage repair in osteoarthritis by delivering miR-216a-5p. Acta Biomater. 2021;122:325–342. doi:10.1016/j.actbio.2020.12.034
  • Yan L, Liu G, Wu X. Exosomes derived from umbilical cord mesenchymal stem cells in mechanical environment show improved osteochondral activity via upregulation of LncRNA H19. J Orthop Translat. 2021;26:111–120. doi:10.1016/j.jot.2020.03.005
  • Zhao C, Chen JY, Peng WM, Yuan B, Bi Q, Xu YJ. Exosomes from adipose‑derived stem cells promote chondrogenesis and suppress inflammation by upregulating miR‑145 and miR‑221. Mol Med Rep. 2020;21(4):1881–1889. doi:10.3892/mmr.2020.10982
  • Cheng X, Zhang G, Zhang L, et al. Mesenchymal stem cells deliver exogenous miR-21 via exosomes to inhibit nucleus pulposus cell apoptosis and reduce intervertebral disc degeneration. J Cell Mol Med. 2018;22(1):261–276. doi:10.1111/jcmm.13316
  • Liao Z, Luo R, Li G, et al. Exosomes from mesenchymal stem cells modulate endoplasmic reticulum stress to protect against nucleus pulposus cell death and ameliorate intervertebral disc degeneration in vivo. Theranostics. 2019;9(14):4084–4100. doi:10.7150/thno.33638
  • Xiang H, Su W, Wu X, et al. Exosomes derived from human urine-derived stem cells inhibit intervertebral disc degeneration by ameliorating endoplasmic reticulum stress. Oxid Med Cell Longev. 2020;2020:6697577. doi:10.1155/2020/6697577
  • Atala A, Kasper FK, Mikos AG. Engineering complex tissues. Sci Transl Med. 2012;4(160):160rv12. doi:10.1126/scitranslmed.3004890
  • Camarero-Espinosa S, Rothen-Rutishauser B, Foster EJ, Weder C. Articular cartilage: from formation to tissue engineering. Biomater Sci. 2016;4(5):734–767. doi:10.1039/C6BM00068A
  • Beris AE, Lykissas MG, Papageorgiou CD, Georgoulis AD. Advances in articular cartilage repair. Injury. 2005;36(Suppl 4):S14–23. doi:10.1016/j.injury.2005.10.007
  • Wasyłeczko M, Sikorska W, Chwojnowski A. Review of synthetic and hybrid scaffolds in cartilage tissue engineering. Membranes. 2020;10(11):100.
  • Moldovan NI, Moldovan L, Raghunath M. Of balls, inks and cages: hybrid biofabrication of 3D tissue analogs. Int J Bioprint. 2019;5(1):167. doi:10.18063/ijb.v5i1.167
  • Laternser S, Keller H, Leupin O, Rausch M, Graf-Hausner U, Rimann M. A novel microplate 3D bioprinting platform for the engineering of muscle and tendon tissues. SLAS Technol. 2018;23(6):599–613. doi:10.1177/2472630318776594
  • Daly AC, Critchley SE, Rencsok EM, Kelly DJ. A comparison of different bioinks for 3D bioprinting of fibrocartilage and hyaline cartilage. Biofabrication. 2016;8(4):045002. doi:10.1088/1758-5090/8/4/045002
  • Thorp H, Kim K, Kondo M, Grainger DW, Okano T. Fabrication of hyaline-like cartilage constructs using mesenchymal stem cell sheets. Sci Rep. 2020;10(1):20869. doi:10.1038/s41598-020-77842-0
  • Chen L, Liu J, Guan M, Zhou T, Duan X, Xiang Z. Growth factor and its polymer scaffold-based delivery system for cartilage tissue engineering. Int J Nanomedicine. 2020;15:6097–6111. doi:10.2147/ijn.S249829
  • Pezzana C, Agnely F, Bochot A, Siepmann J, Menasché P. Extracellular vesicles and biomaterial design: new therapies for cardiac repair. Trends Mol Med. 2021;27(3):231–247. doi:10.1016/j.molmed.2020.10.006
  • Chuang E-Y, Chiang C-W, Wong P-C, Chen C-H. Hydrogels for the application of articular cartilage tissue engineering: a review of hydrogels. Adv Mater Sci Engine. 2018;2018:4368910. doi:10.1155/2018/4368910
  • Liu X, Yang Y, Li Y, et al. Integration of stem cell-derived exosomes with in situ hydrogel glue as a promising tissue patch for articular cartilage regeneration. Nanoscale. 2017;9(13):4430–4438. doi:10.1039/c7nr00352h
  • Chen P, Zheng L, Wang Y, et al. Desktop-stereolithography 3D printing of a radially oriented extracellular matrix/mesenchymal stem cell exosome bioink for osteochondral defect regeneration. Theranostics. 2019;9(9):2439–2459. doi:10.7150/thno.31017
  • Du X, Cai L, Xie J, Zhou X. The role of TGF-beta 3 in cartilage development and osteoarthritis. Bone Res. 2023;11(1):2. doi:10.1038/s41413-022-00239-4
  • Li T, Liu B, Chen K, Lou Y, Jiang Y, Zhang D. Small molecule compounds promote the proliferation of chondrocytes and chondrogenic differentiation of stem cells in cartilage tissue engineering. Biomed Pharmacother. 2020;131:110652. doi:10.1016/j.biopha.2020.110652
  • Chawla S, Mainardi A, Majumder N, et al. Chondrocyte hypertrophy in osteoarthritis: mechanistic studies and models for the identification of new therapeutic strategies. Cells. 2022;11(24):248.
  • Johnson K, Zhu S, Tremblay MS, et al. A stem cell-based approach to cartilage repair. Science. 2012;336(6082):717–721. doi:10.1126/science.1215157
  • Zheng Z, Chen F, Zhang X. Editorial: potential of extracellular matrix molecules in pharmaceutical development. Editorial. Front Pharmacol. 2021;11. doi:10.3389/fphar.2020.636026
  • Gao Y, Liu S, Huang J, et al. The ECM-cell interaction of cartilage extracellular matrix on chondrocytes. Biomed Res Int. 2014;2014:648459. doi:10.1155/2014/648459
  • Shi Y, Hu X, Cheng J, et al. A small molecule promotes cartilage extracellular matrix generation and inhibits osteoarthritis development. Nat Commun. 2019;10(1):1914. doi:10.1038/s41467-019-09839-x
  • Zhang W, Chen R, Xu X, et al. Construction of biocompatible hydrogel scaffolds with a long-term drug release for facilitating cartilage repair. Front Pharmacol. 2022;13:922032. doi:10.3389/fphar.2022.922032
  • Xu X, Shi D, Shen Y, et al. Full-thickness cartilage defects are repaired via a microfracture technique and intraarticular injection of the small-molecule compound kartogenin. Arthritis Res Ther. 2015;17(1):20. doi:10.1186/s13075-015-0537-1
  • Yan H, Yu T, Li J, et al. Kartogenin improves osteogenesis of bone marrow mesenchymal stem cells via autophagy. Stem Cells Int. 2022;2022:1278921. doi:10.1155/2022/1278921
  • Zhang H, Fang W, Zhao T, et al. Real-time MRI monitoring of GelMA-based hydrogel-loaded kartogenin for in situ cartilage regeneration. Front Bioeng Biotechnol. 2022;10:940735. doi:10.3389/fbioe.2022.940735
  • Yano F, Hojo H, Ohba S, et al. A novel disease-modifying osteoarthritis drug candidate targeting Runx1. Ann Rheum Dis. 2013;72(5):748–753. doi:10.1136/annrheumdis-2012-201745
  • Park J, Lee SY. A review of osteoarthritis signaling intervention using small-molecule inhibitors. Medicine. 2022;101(32):e29501. doi:10.1097/md.0000000000029501
  • Zhang Y, Zhao Q. Salidroside attenuates interleukin-1β-induced inflammation in human osteoarthritis chondrocytes. J Cell Biochem. 2018. doi:10.1002/jcb.27076
  • Wu M, Hu R, Wang J, et al. Salidroside suppresses IL-1β-induced apoptosis in chondrocytes via phosphatidylinositol 3-kinases (PI3K)/Akt signaling inhibition. Med Sci Monit. 2019;25:5833–5840. doi:10.12659/msm.917851
  • Nagao M, Hamilton JL, Kc R, et al. Vascular endothelial growth factor in cartilage development and osteoarthritis. Sci Rep. 2017;7(1):13027. doi:10.1038/s41598-017-13417-w
  • Carmeliet P, Jain RK. Molecular mechanisms and clinical applications of angiogenesis. Nature. 2011;473(7347):298–307. doi:10.1038/nature10144
  • Ngo HX, Garneau-Tsodikova S. What are the drugs of the future? Medchemcomm. 2018;9(5):757–758. doi:10.1039/c8md90019a
  • da Costa BR, Pereira TV, Saadat P, et al. Effectiveness and safety of non-steroidal anti-inflammatory drugs and opioid treatment for knee and Hip osteoarthritis: network meta-analysis. BMJ. 2021;375:n2321. doi:10.1136/bmj.n2321
  • da Costa BR, Reichenbach S, Keller N, et al. Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and Hip osteoarthritis: a network meta-analysis. Lancet. 2017;390(10090):e21–e33. doi:10.1016/s0140-6736(17)31744-0
  • Magni A, Agostoni P, Bonezzi C, et al. Management of osteoarthritis: expert opinion on NSAIDs. Pain Ther. 2021;10(2):783–808. doi:10.1007/s40122-021-00260-1
  • Jüni P, Hari R, Rutjes AW, et al. Intra-articular corticosteroid for knee osteoarthritis. Cochrane Database Syst Rev. 2015;2015(10):Cd005328. doi:10.1002/14651858.CD005328.pub3
  • Smedslund G, Kjeken I, Musial F, Sexton J, Østerås N. Interventions for osteoarthritis pain: a systematic review with network meta-analysis of existing cochrane reviews. Osteoarthr Cartil Open. 2022;4(2):100242. doi:10.1016/j.ocarto.2022.100242
  • Garg N, Perry L, Deodhar A. Intra-articular and soft tissue injections, a systematic review of relative efficacy of various corticosteroids. Clin Rheumatol. 2014;33(12):1695–1706. doi:10.1007/s10067-014-2572-8
  • McAlindon TE, Bannuru RR, Sullivan MC, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthritis Cartilage. 2014;22(3):363–388. doi:10.1016/j.joca.2014.01.003
  • Bannuru RR, Osani MC, Vaysbrot EE, et al. OARSI guidelines for the non-surgical management of knee, Hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage. 2019;27(11):1578–1589. doi:10.1016/j.joca.2019.06.011
  • Evaniew N, Simunovic N, Karlsson J. Cochrane in CORR®: viscosupplementation for the treatment of osteoarthritis of the knee. Clin Orthop Relat Res. 2014;472(7):2028–2034. doi:10.1007/s11999-013-3378-8
  • Presti D, Scott JE. Hyaluronan-mediated protective effect against cell damage caused by enzymatically produced hydroxyl (OH.) radicals is dependent on hyaluronan molecular mass. Cell Biochem Funct. 1994;12(4):281–288. doi:10.1002/cbf.290120409
  • Pereira TV, Jüni P, Saadat P, et al. Viscosupplementation for knee osteoarthritis: systematic review and meta-analysis. BMJ. 2022;378:e069722. doi:10.1136/bmj-2022-069722
  • Jackson DW, Evans NA, Thomas BM. Accuracy of needle placement into the intra-articular space of the knee. J Bone Joint Surg Am. 2002;84(9):1522–1527. doi:10.2106/00004623-200209000-00003
  • Patel A, Chadwick N, von Beck K, et al. Ultrasound-guided joint interventions of the lower extremity. Skeletal Radiol. 2022. doi:10.1007/s00256-022-04168-5
  • Hussein M. An accurate full-flexion anterolateral portal for needle placement in the knee joint with dry osteoarthritis. J Am Acad Orthop Surg. 2017;25(7):e131–e137. doi:10.5435/jaaos-d-16-00338
  • Telikicherla M, Kamath SU. Accuracy of needle placement into the intra-articular space of the knee in osteoarthritis patients for viscosupplementation. J Clin Diagn Res. 2016;10(2):Rc15–7. doi:10.7860/jcdr/2016/17127.7275
  • Toda Y, Tsukimura N. A comparison of intra-articular hyaluronan injection accuracy rates between three approaches based on radiographic severity of knee osteoarthritis. Osteoarthritis Cartilage. 2008;16(9):980–985. doi:10.1016/j.joca.2008.01.003
  • Reeves KD, Sit RW, Rabago DP. Dextrose prolotherapy: a narrative review of basic science, clinical research, and best treatment recommendations. Phys Med Rehabil Clin N Am. 2016;27(4):783–823. doi:10.1016/j.pmr.2016.06.001
  • Sit RW, Chung V, Reeves KD, et al. Hypertonic dextrose injections (prolotherapy) in the treatment of symptomatic knee osteoarthritis: a systematic review and meta-analysis. Sci Rep. 2016;6:25247. doi:10.1038/srep25247
  • Wang J, Liang J, Yao J, et al. Meta-analysis of clinical trials focusing on hypertonic dextrose prolotherapy (HDP) for knee osteoarthritis. Aging Clin Exp Res. 2022;34(4):715–724. doi:10.1007/s40520-021-01963-3
  • Uebelhart D, Thonar EJ, Delmas PD, Chantraine A, Vignon E. Effects of oral chondroitin sulfate on the progression of knee osteoarthritis: a pilot study. Osteoarthritis Cartilage. 1998;6(Suppl A):39–46. doi:10.1016/s1063-4584(98)80011-3
  • Urbi Z, Azmi NS, Ming LC, Hossain MS. A concise review of extraction and characterization of chondroitin sulphate from fish and fish wastes for pharmacological application. Curr Issues Mol Biol. 2022;44(9):3905–3922. doi:10.3390/cimb44090268
  • Gallagher B, Tjoumakaris FP, Harwood MI, Good RP, Ciccotti MG, Freedman KB. Chondroprotection and the prevention of osteoarthritis progression of the knee: a systematic review of treatment agents. Am J Sports Med. 2015;43(3):734–744. doi:10.1177/0363546514533777
  • Simental-Mendía M, Sánchez-García A, Vilchez-Cavazos F, Acosta-Olivo CA, Peña-Martínez VM, Simental-Mendía LE. Effect of glucosamine and chondroitin sulfate in symptomatic knee osteoarthritis: a systematic review and meta-analysis of randomized placebo-controlled trials. Rheumatol Int. 2018;38(8):1413–1428. doi:10.1007/s00296-018-4077-2
  • Honvo G, Bruyère O, Geerinck A, Veronese N, Reginster JY. Efficacy of chondroitin sulfate in patients with knee osteoarthritis: a comprehensive meta-analysis exploring inconsistencies in randomized, placebo-controlled trials. Adv Ther. 2019;36(5):1085–1099. doi:10.1007/s12325-019-00921-w
  • Nelson AE, Allen KD, Golightly YM, Goode AP, Jordan JM. A systematic review of recommendations and guidelines for the management of osteoarthritis: the chronic osteoarthritis management initiative of the US bone and joint initiative. Semin Arthritis Rheum. 2014;43(6):701–712. doi:10.1016/j.semarthrit.2013.11.012
  • Smith JK. Exercise as an adjuvant to cartilage regeneration therapy. Int J Mol Sci. 2020;21(24):9471. doi:10.3390/ijms21249471
  • Chen J, Zhou R, Feng Y, Cheng L. Molecular mechanisms of exercise contributing to tissue regeneration. Signal Transduct Target Ther. 2022;7(1):383. doi:10.1038/s41392-022-01233-2
  • Sánchez Romero EA, Fernández-Carnero J, Calvo-Lobo C, Ochoa Sáez V, Burgos Caballero V, Pecos-Martín D. Is a combination of exercise and dry needling effective for knee OA? Pain Med. 2020;21(2):349–363. doi:10.1093/pm/pnz036
  • Alonso Pérez JL, Martín Pérez S, Battaglino A, Villafañe JH, Alonso-Sal A, Sánchez Romero EA. An up-date of the muscle strengthening exercise effectiveness in postmenopausal women with osteoporosis: a qualitative systematic review. J Clin Med. 2021;10(11):2229. doi:10.3390/jcm10112229
  • Cantero-Tellez R, García-Orza S, Sánchez Romero EA, Battaglino A, Cruz-Gambero L, Cuadros-Romero M. Effect of a proprioceptive exercise program on force sense for carpometacarpal joint osteoarthritis: a pilot study. Top Geriatr Rehabil. 2021;37(4):222–226. doi:10.1097/TGR.0000000000000336
  • Sánchez-Romero EA, González-Zamorano Y, Arribas-Romano A, et al. Efficacy of manual therapy on facilitatory nociception and endogenous pain modulation in older adults with knee osteoarthritis: a case series. Appl Sci. 2021;11(4):1895. doi:10.3390/app11041895
  • Sinatti P, Sánchez Romero EA, Martínez-Pozas O, Villafañe JH. Effects of patient education on pain and function and its impact on conservative treatment in elderly patients with pain related to hip and knee osteoarthritis: a systematic review. Int J Environ Res Public Health. 2022;19(10):6194. doi:10.3390/ijerph19106194
  • Nguyen C, Lefèvre-Colau MM, Poiraudeau S, Rannou F. Rehabilitation (exercise and strength training) and osteoarthritis: a critical narrative review. Ann Phys Rehabil Med. 2016;59(3):190–195. doi:10.1016/j.rehab.2016.02.010
  • Sharma L. Osteoarthritis year in review 2015: clinical. Osteoarthritis Cartilage. 2016;24(1):36–48. doi:10.1016/j.joca.2015.07.026
  • Duivenvoorden T, Brouwer RW, van Raaij TM, Verhagen AP, Verhaar JA, Bierma-Zeinstra SM. Braces and orthoses for treating osteoarthritis of the knee. Cochrane Database Syst Rev. 2015;2015(3):Cd004020. doi:10.1002/14651858.CD004020.pub3
  • Hunter CW, Deer TR, Jones MR, et al. Consensus guidelines on interventional therapies for knee pain (STEP Guidelines) from the American Society of Pain and Neuroscience. J Pain Res. 2022;15:2683–2745. doi:10.2147/jpr.S370469
  • Anandacoomarasamy A, Leibman S, Smith G, et al. Weight loss in obese people has structure-modifying effects on medial but not on lateral knee articular cartilage. Ann Rheum Dis. 2012;71(1):26–32. doi:10.1136/ard.2010.144725
  • Aaboe J, Bliddal H, Messier SP, Alkjær T, Henriksen M. Effects of an intensive weight loss program on knee joint loading in obese adults with knee osteoarthritis. Osteoarthritis Cartilage. 2011;19(7):822–828. doi:10.1016/j.joca.2011.03.006