{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:24:00Z","timestamp":1787315040693,"version":"build-2736575974"},"reference-count":218,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T00:00:00Z","timestamp":1726012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health"},{"name":"Department of Defense"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Treating cartilage damage is challenging as its ability for self-regeneration is limited. Left untreated, it can progress to osteoarthritis (OA), a joint disorder characterized by the deterioration of articular cartilage and other joint tissues. Surgical options, such as microfracture and cell\/tissue transplantation, have shown promise as techniques to harness the body\u2019s endogenous regenerative capabilities to promote cartilage repair. Nonetheless, these techniques have been scrutinized due to reported inconsistencies in long-term outcomes and the tendency for the defects to regenerate as fibrocartilage instead of the smooth hyaline cartilage native to joint surfaces. Orthobiologics are medical therapies that utilize biologically derived substances to augment musculoskeletal healing. These treatments are rising in popularity because of their potential to enhance surgical standards of care. More recent developments in orthobiologics have focused on the role of exosomes in articular cartilage repair. Exosomes are nano-sized extracellular vesicles containing cargo such as proteins, lipids, and nucleic acids, and are known to facilitate intercellular communication, though their regenerative potential still needs to be fully understood. This review aims to demonstrate the advancements in cartilage regeneration, highlight surgical and biological treatment options, and discuss the recent strides in understanding the precise mechanisms of action involved.<\/jats:p>","DOI":"10.3390\/life14091149","type":"journal-article","created":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T05:45:12Z","timestamp":1726033512000},"page":"1149","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Enhancing Cartilage Repair: Surgical Approaches, Orthobiologics, and the Promise of Exosomes"],"prefix":"10.3390","volume":"14","author":[{"given":"Jacob","family":"Singer","sequence":"first","affiliation":[{"name":"Linda and Mitch Hart Regenerative and Personalized Medicine, Steadman Philippon Research Institute, Vail, CO 81657, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9009-0043","authenticated-orcid":false,"given":"Noah","family":"Knezic","sequence":"additional","affiliation":[{"name":"Linda and Mitch Hart Regenerative and Personalized Medicine, Steadman Philippon Research Institute, Vail, CO 81657, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9245-0989","authenticated-orcid":false,"given":"Jonathan","family":"Layne","sequence":"additional","affiliation":[{"name":"Linda and Mitch Hart Regenerative and Personalized Medicine, Steadman Philippon Research Institute, Vail, CO 81657, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greta","family":"Gohring","sequence":"additional","affiliation":[{"name":"Linda and Mitch Hart Regenerative and Personalized Medicine, Steadman Philippon Research Institute, Vail, CO 81657, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff","family":"Christiansen","sequence":"additional","affiliation":[{"name":"Linda and Mitch Hart Regenerative and Personalized Medicine, Steadman Philippon Research Institute, Vail, CO 81657, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Rothrauff","sequence":"additional","affiliation":[{"name":"Linda and Mitch Hart Regenerative and Personalized Medicine, Steadman Philippon Research Institute, Vail, CO 81657, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnny","family":"Huard","sequence":"additional","affiliation":[{"name":"Linda and Mitch Hart Regenerative and Personalized Medicine, Steadman Philippon Research Institute, Vail, CO 81657, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6850","DOI":"10.1111\/febs.15776","article-title":"A guide to the composition and functions of the extracellular matrix","volume":"288","author":"Karamanos","year":"2021","journal-title":"FEBS J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"177","DOI":"10.3390\/jdb3040177","article-title":"Role of chondrocytes in cartilage formation, progression of osteoarthritis and cartilage regeneration","volume":"3","author":"Akkiraju","year":"2015","journal-title":"J. Dev. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1177\/1941738109350438","article-title":"The basic science of articular cartilage: Structure, composition, and function","volume":"1","author":"Bedi","year":"2009","journal-title":"Sports Health"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Medvedeva, E.V., Grebenik, E.A., Gornostaeva, S.N., Telpuhov, V.I., Lychagin, A.V., Timashev, P.S., and Chagin, A.S. (2018). Repair of damaged articular cartilage: Current approaches and future directions. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082366"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1172\/JCI70050","article-title":"Bone marrow mesenchymal stem cells and TGF-\u03b2 signaling in bone remodeling","volume":"124","author":"Crane","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/20417314231164765","article-title":"Regeneration of articular cartilage defects: Therapeutic strategies and perspectives","volume":"14","author":"Guo","year":"2023","journal-title":"J. Tissue Eng."},{"key":"ref_7","first-page":"9","article-title":"Immunolocalization of matrix proteins in different human cartilage subtypes","volume":"21","author":"Wachsmuth","year":"2006","journal-title":"Histol. Histopathol."},{"key":"ref_8","first-page":"753","article-title":"The cell density of human articular and costal cartilage","volume":"101","author":"Stockwell","year":"1967","journal-title":"J. Anat."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1056\/NEJM197412122912406","article-title":"The reaction of articular cartilage to injury and osteoarthritis","volume":"291","author":"Mankin","year":"1974","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.matbio.2018.05.005","article-title":"Cartilage diseases","volume":"71\u201372","author":"Krishnan","year":"2018","journal-title":"Matrix Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1002\/bdrc.20050","article-title":"Mechanisms of synovial joint and articular cartilage formation: Recent advances, but many lingering mysteries","volume":"75","author":"Pacifici","year":"2005","journal-title":"Birth Defects Res. Part C Embryo Today Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1007\/s00018-005-5217-x","article-title":"Aggrecan, aging and assembly in articular cartilage","volume":"62","author":"Dudhia","year":"2005","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1113\/expphysiol.1996.sp003956","article-title":"The cellular physiology of articular cartilage","volume":"81","author":"Hall","year":"1996","journal-title":"Exp. Physiol. Transl. Integr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1177\/03635465980260022701","article-title":"Articular cartilage repair","volume":"26","author":"Newman","year":"1998","journal-title":"Am. J. Sports Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.semcdb.2016.10.005","article-title":"Articular cartilage and joint development from embryogenesis to adulthood","volume":"62","author":"Decker","year":"2017","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/ar396","article-title":"The life cycle of chondrocytes in the developing skeleton","volume":"4","author":"Shum","year":"2001","journal-title":"Arthritis Res. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1083\/jcb.8.3.719","article-title":"Chondrogenesis, studied with the electron microscope","volume":"8","author":"Godman","year":"1960","journal-title":"J. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1083\/jcb.102.4.1151","article-title":"Collagen gene expression during limb cartilage differentiation","volume":"102","author":"Kosher","year":"1986","journal-title":"J. Cell Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1053\/joca.1998.0129","article-title":"Differential effects of local application of BMP-2 or TGF-\u03b21 on both articular cartilage composition and osteophyte formation","volume":"6","author":"Glansbeek","year":"1998","journal-title":"Osteoarthr. Cartil."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Tekari, A., Luginbuehl, R., Hofstetter, W., and Egli, R.J. (2015). Transforming growth factor beta signaling is essential for the autonomous formation of cartilage-like tissue by expanded chondrocytes. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0120857"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1177\/0363546519898681","article-title":"Biologically regulated marrow stimulation by blocking TGF-\u03b21 with losartan oral administration results in hyaline-like cartilage repair: A rabbit osteochondral defect model","volume":"48","author":"Utsunomiya","year":"2020","journal-title":"Am. J. Sports Med."},{"key":"ref_22","first-page":"e78","article-title":"In vivo comparison of the effects of rhBMP-2 and rhBMP-4 in osteochondral tissue regeneration","volume":"20","author":"Abarrategi","year":"2010","journal-title":"Eur. Cells Mater."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1002\/(SICI)1097-4636(19980615)40:4<614::AID-JBM13>3.0.CO;2-F","article-title":"Osteogenic protein (OP-1, BMP-7) stimulates cartilage differentiation of human and goat perichondrium tissue in vitro","volume":"40","author":"Louwerse","year":"1998","journal-title":"J. Biomed. Mater. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1042\/bj2400423","article-title":"Stimulation of proteoglycan biosynthesis by serum and insulin-like growth factor-I in cultured bovine articular cartilage","volume":"240","author":"McQuillan","year":"1986","journal-title":"Biochem. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1006\/abbi.1994.1020","article-title":"Differential effects of bFGF and IGF-I on matrix metabolism in calf and adult bovine cartilage explants","volume":"308","author":"Sah","year":"1994","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_26","first-page":"64","article-title":"Suppression of intra-articular responses to interleukin-1 by transfer of the interleukin-1 receptor antagonist gene to synovium","volume":"1","author":"Hung","year":"1994","journal-title":"Gene Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1016\/j.joca.2017.08.004","article-title":"Sprifermin (rhFGF18) enables proliferation of chondrocytes producing a hyaline cartilage matrix","volume":"25","author":"Gigout","year":"2017","journal-title":"Osteoarthr. Cartil."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1002\/jbmr.2828","article-title":"Targeting VEGF and its receptors for the treatment of osteoarthritis and associated pain","volume":"31","author":"Hamilton","year":"2016","journal-title":"J. Bone Miner. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.joca.2005.10.011","article-title":"A review of the effects of insulin-like growth factor and platelet derived growth factor on in vivo cartilage healing and repair","volume":"14","author":"Schmidt","year":"2006","journal-title":"Osteoarthr. Cartil."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s11926-019-0868-z","article-title":"Adipokines: New therapeutic target for osteoarthritis?","volume":"21","author":"Xie","year":"2019","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"101658","DOI":"10.1016\/j.bonr.2023.101658","article-title":"Post-traumatic osteoarthritis: A review of pathogenic mechanisms and novel targets for mitigation","volume":"18","author":"Dilley","year":"2023","journal-title":"Bone Rep."},{"key":"ref_32","unstructured":"GBD 2019 Diseases and Injuries Collaborators (2020). Global burden of 369 diseases and injuries in 204 countries and territories, 1990\u20132019: A systematic analysis for the Global Burden of Disease Study 2019. Lancet, 396, 1204\u20131222."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1001\/jama.2017.15927","article-title":"Factors associated with increases in US health care spending, 1996\u20132013","volume":"318","author":"Dieleman","year":"2017","journal-title":"JAMA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1001\/jama.2020.0734","article-title":"US health care spending by payer and health condition, 1996\u20132016","volume":"323","author":"Dieleman","year":"2020","journal-title":"JAMA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1016\/S0140-6736(11)60243-2","article-title":"Osteoarthritis: An update with relevance for clinical practice","volume":"377","author":"Bijlsma","year":"2011","journal-title":"Lancet"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1002\/jor.21359","article-title":"Post-traumatic osteoarthritis: Improved understanding and opportunities for early intervention","volume":"29","author":"Anderson","year":"2011","journal-title":"J. Orthop. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1097\/01.bot.0000246468.80635.ef","article-title":"Posttraumatic osteoarthritis: A first estimate of incidence, prevalence, and burden of disease","volume":"20","author":"Brown","year":"2006","journal-title":"J. Orthop. Trauma"},{"key":"ref_38","first-page":"237","article-title":"The role of cytokines in osteoarthritis pathophysiology","volume":"39","author":"Fernandes","year":"2002","journal-title":"Biorheology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1038\/s41584-022-00749-9","article-title":"Synovial inflammation in osteoarthritis progression","volume":"18","author":"Coras","year":"2022","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.coph.2016.02.009","article-title":"New developments in osteoarthritis and cartilage biology","volume":"28","author":"Poulet","year":"2016","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1007\/s40122-021-00260-1","article-title":"Management of Osteoarthritis: Expert Opinion on NSAIDs","volume":"10","author":"Magni","year":"2021","journal-title":"Pain Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1053\/joca.2002.0801","article-title":"Articular cartilage repair: Basic science and clinical progress. A review of the current status and prospects","volume":"10","author":"Hunziker","year":"2002","journal-title":"Osteoarthr. Cartil."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1002\/cphy.c180020","article-title":"Mechanosensing and mechanoregulation of endothelial cell functions","volume":"9","author":"Fang","year":"2019","journal-title":"Compr. Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1160\/TH16-04-0300","article-title":"The prowess of platelets in immunity and inflammation","volume":"116","author":"Koenen","year":"2016","journal-title":"Thromb. Haemost."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"6692","DOI":"10.1016\/j.biomaterials.2011.05.078","article-title":"Immune responses to implants\u2013a review of the implications for the design of immunomodulatory biomaterials","volume":"32","author":"Franz","year":"2011","journal-title":"Biomaterials"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"585","DOI":"10.3109\/17453674.2013.854666","article-title":"Toll-like receptors in human chondrocytes and osteoarthritic cartilage","volume":"84","author":"Sillat","year":"2013","journal-title":"Acta Orthop."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2152","DOI":"10.1002\/art.21951","article-title":"The catabolic pathway mediated by Toll-like receptors in human osteoarthritic chondrocytes","volume":"54","author":"Kim","year":"2006","journal-title":"Arthritis Rheum. Off. J. Am. Coll. Rheumatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s11926-017-0672-6","article-title":"Innate immune responses and osteoarthritis","volume":"19","author":"Kalaitzoglou","year":"2017","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"192415","DOI":"10.1155\/2015\/192415","article-title":"Recognition of immune response for the early diagnosis and treatment of osteoarthritis","volume":"2015","author":"Kandahari","year":"2015","journal-title":"J. Immunol. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/jor.24457","article-title":"Role of inflammation and the immune system in the progression of osteoarthritis","volume":"38","author":"Sommerfeld","year":"2020","journal-title":"J. Orthop. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.addr.2018.12.015","article-title":"Articular fibrocartilage\u2014Why does hyaline cartilage fail to repair?","volume":"146","author":"Armiento","year":"2019","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0074-7696(04)33001-9","article-title":"Biology of fibrocartilage cells","volume":"233","author":"Benjamin","year":"2004","journal-title":"Int. Rev. Cytol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Yasui, N., and Nimni, M.E. (2018). Cartilage collagens. Collagen, CRC Press.","DOI":"10.1201\/9781351070799-10"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1055\/s-0030-1248228","article-title":"The future of cartilage restoration","volume":"17","author":"Sgaglione","year":"2004","journal-title":"J. Knee Surg."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s11914-015-0290-z","article-title":"Articular cartilage: Structural and developmental intricacies and questions","volume":"13","author":"Decker","year":"2015","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/j.actbio.2007.04.005","article-title":"Mechanical properties of hyaline and repair cartilage studied by nanoindentation","volume":"3","author":"Franke","year":"2007","journal-title":"Acta Biomater."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Davis, S., Roldo, M., Blunn, G., Tozzi, G., and Roncada, T. (2021). Influence of the mechanical environment on the regeneration of osteochondral defects. Front. Bioeng. Biotechnol., 9.","DOI":"10.3389\/fbioe.2021.603408"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"S271","DOI":"10.1097\/00003086-200110001-00025","article-title":"Matrices for cartilage repair","volume":"391","author":"Coutts","year":"2001","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.joca.2008.07.004","article-title":"Hyaline cartilage cells outperform mandibular condylar cartilage cells in a TMJ fibrocartilage tissue engineering application","volume":"17","author":"Wang","year":"2009","journal-title":"Osteoarthr. Cartil."},{"key":"ref_60","first-page":"4830","article-title":"Articular cartilage and osteochondral tissue engineering techniques: Recent advances and challenges","volume":"6","author":"Wei","year":"2021","journal-title":"Bioact. Mater."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.cpm.2022.02.001","article-title":"Types of fibrocartilage","volume":"39","author":"Buchanan","year":"2022","journal-title":"Clin. Podiatr. Med. Surg."},{"key":"ref_62","first-page":"189","article-title":"Current concepts in the treatment of cartilage damage. A review","volume":"118","author":"Musumeci","year":"2013","journal-title":"Ital. J. Anat. Embryol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1302\/0301-620X.87B4.15971","article-title":"A clinical review of cartilage repair techniques","volume":"87","author":"Smith","year":"2005","journal-title":"J. Bone Jt. Surg. Br. Vol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/nrrheum.2014.157","article-title":"Repair and tissue engineering techniques for articular cartilage","volume":"11","author":"Makris","year":"2015","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1177\/1759720X12448454","article-title":"Chondrogenesis, chondrocyte differentiation, and articular cartilage metabolism in health and osteoarthritis","volume":"4","author":"Goldring","year":"2012","journal-title":"Ther. Adv. Musculoskelet. Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"S362","DOI":"10.1097\/00003086-200110001-00033","article-title":"Microfracture: Surgical technique and rehabilitation to treat chondral defects","volume":"391","author":"Steadman","year":"2001","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/S1048-6666(97)80033-X","article-title":"Microfracture technique forfull-thickness chondral defects: Technique and clinical results","volume":"7","author":"Steadman","year":"1997","journal-title":"Oper. Tech. Orthop."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1177\/1947603510365533","article-title":"Microfracture: Its history and experience of the developing surgeon","volume":"1","author":"Steadman","year":"2010","journal-title":"Cartilage"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/s41413-021-00147-z","article-title":"Subchondral bone microenvironment in osteoarthritis and pain","volume":"9","author":"Hu","year":"2021","journal-title":"Bone Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1002\/jcb.20652","article-title":"The control of chondrogenesis","volume":"97","author":"Goldring","year":"2006","journal-title":"J. Cell. Biochem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1097\/00132585-200311040-00004","article-title":"Microfracture Chondroplasty: Indications, Techniques, and Outcomes","volume":"11","author":"Steadman","year":"2003","journal-title":"Sports Med. Arthrosc. Rev."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S0278-5919(05)70130-7","article-title":"Osteochondral allograft transplantation","volume":"18","author":"Bugbee","year":"1999","journal-title":"Clin. Sports Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1055\/s-0037-1618592","article-title":"Cartilage restoration: Microfracture and osteochondral autograft transplantation","volume":"31","author":"Redondo","year":"2018","journal-title":"J. Knee Surg."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.pmr.2022.08.016","article-title":"Regulatory Considerations of Orthobiologic Procedures","volume":"34","author":"Jang","year":"2023","journal-title":"Phys. Med. Rehabil. Clin."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/23259671221101626","article-title":"Regulatory and Ethical Aspects of Orthobiologic Therapies","volume":"10","author":"Murray","year":"2022","journal-title":"Orthop. J. Sports Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1002\/cpt.549","article-title":"Emerging translation of regenerative therapies","volume":"101","author":"Allickson","year":"2017","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Jessop, Z.M., Al-Sabah, A., Francis, W.R., and Whitaker, I.S. (2016). Transforming healthcare through regenerative medicine. BMC Med., 14.","DOI":"10.1186\/s12916-016-0669-4"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1177\/03635465211061606","article-title":"The biological use of platelet-rich plasma in skeletal muscle injury and repair","volume":"51","author":"Boivin","year":"2023","journal-title":"Am. J. Sports Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1089\/ten.teb.2019.0292","article-title":"Platelet-rich plasma therapy in the treatment of diseases associated with orthopedic injuries","volume":"26","author":"Fang","year":"2020","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1517\/14712598.2015.1038234","article-title":"Platelet-rich plasma in the treatment of skeletal muscle injuries","volume":"15","author":"Andia","year":"2015","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/S0889-8588(18)30580-X","article-title":"Structure and function of the bone marrow and hematopoiesis","volume":"2","author":"Gulati","year":"1988","journal-title":"Hematol.\/Oncol. Clin."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e441","DOI":"10.1016\/j.eats.2016.10.024","article-title":"Bone marrow aspirate concentrate harvesting and processing technique","volume":"6","author":"Chahla","year":"2017","journal-title":"Arthrosc. Tech."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1007\/s00264-020-04703-w","article-title":"Bone marrow concentrate injections for the treatment of osteoarthritis: Evidence from preclinical findings to the clinical application","volume":"45","author":"Cavallo","year":"2021","journal-title":"Int. Orthop."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.2106\/JBJS.I.01284","article-title":"Concentrated bone marrow aspirate improves full-thickness cartilage repair compared with microfracture in the equine model","volume":"92","author":"Fortier","year":"2010","journal-title":"JBJS"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1186\/s13287-020-01781-w","article-title":"Bone marrow mesenchymal stem cell-derived exosomes protect cartilage damage and relieve knee osteoarthritis pain in a rat model of osteoarthritis","volume":"11","author":"He","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1177\/0363546515609597","article-title":"Bone marrow concentrate improves early cartilage phase maturation of a scaffold plug in the knee: A comparative magnetic resonance imaging analysis to platelet-rich plasma and control","volume":"44","author":"Krych","year":"2016","journal-title":"Am. J. Sports Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1089\/scd.2012.0373","article-title":"Clinical use of bone marrow, bone marrow concentrate, and expanded bone marrow mesenchymal stem cells in cartilage disease","volume":"22","author":"Veronesi","year":"2013","journal-title":"Stem Cells Dev."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/2473011417S000055","article-title":"Effects of Micronized Cartilage Matrix on Cartilage Repair in Osteochondral Lesions of the Talus","volume":"2","author":"Kreulen","year":"2017","journal-title":"Foot Ankle Orthop."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s10856-006-0059-0","article-title":"Mineralised collagen\u2014An artificial, extracellular bone matrix\u2014Improves osteogenic differentiation of bone marrow stromal cells","volume":"19","author":"Bernhardt","year":"2008","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1089\/ten.tec.2016.0276","article-title":"Development of a micronized meniscus extracellular matrix scaffold for potential augmentation of meniscal repair and regeneration","volume":"22","author":"Monibi","year":"2016","journal-title":"Tissue Eng. Part C Methods"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"e519","DOI":"10.1016\/j.eats.2014.05.014","article-title":"Treatment of glenoid chondral defect using micronized allogeneic cartilage matrix implantation","volume":"3","author":"Shin","year":"2014","journal-title":"Arthrosc. Tech."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/2041731413508668","article-title":"Reconstitution of bone-like matrix in osteogenically differentiated mesenchymal stem cell\u2013collagen constructs: A three-dimensional in vitro model to study hematopoietic stem cell niche","volume":"4","author":"Lai","year":"2013","journal-title":"J. Tissue Eng."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Bretschneider, H., Quade, M., Lode, A., Gelinsky, M., Rammelt, S., and Vater, C. (2021). Chemotactic and angiogenic potential of mineralized collagen scaffolds functionalized with naturally occurring bioactive factor mixtures to stimulate bone regeneration. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115836"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.csm.2018.09.002","article-title":"Ortho-biologics for osteoarthritis","volume":"38","author":"Huebner","year":"2019","journal-title":"Clin. Sports Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1007\/s00264-023-05803-z","article-title":"Orthobiologics: A review","volume":"47","author":"Mavrogenis","year":"2023","journal-title":"Int. Orthop."},{"key":"ref_96","first-page":"30","article-title":"Losartan protects against osteoarthritis by repressing the TGF-\u03b21 signaling pathway via upregulation of PPAR\u03b3","volume":"29","author":"Deng","year":"2021","journal-title":"J. Orthop. Transl."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1186\/s13075-014-0427-y","article-title":"Bevacizumab, an anti-vascular endothelial growth factor antibody, inhibits osteoarthritis","volume":"16","author":"Nagai","year":"2014","journal-title":"Arthritis Res. Ther."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Park, S., Kim, B.-K., and Park, S.-K. (2022). Effects of fisetin, a plant-derived flavonoid, on response to oxidative stress, aging, and age-related diseases in Caenorhabditis elegans. Pharmaceuticals, 15.","DOI":"10.3390\/ph15121528"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1056\/NEJM199411103311907","article-title":"Transforming growth factor \u03b2 in tissue fibrosis","volume":"331","author":"Border","year":"1994","journal-title":"N. Engl. J. Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1177\/03635465211008655","article-title":"The beneficial effect of an intra-articular injection of losartan on microfracture-mediated cartilage repair is dose dependent","volume":"49","author":"Logan","year":"2021","journal-title":"Am. J. Sports Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.joca.2022.11.014","article-title":"The effects of losartan or angiotensin II receptor antagonists on cartilage: A systematic review","volume":"31","author":"Yamaura","year":"2023","journal-title":"Osteoarthr. Cartil."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"16009","DOI":"10.1038\/boneres.2016.9","article-title":"TGF-\u03b2 and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease","volume":"4","author":"Wu","year":"2016","journal-title":"Bone Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/s41413-017-0005-4","article-title":"Transforming growth factor-\u03b2 in stem cells and tissue homeostasis","volume":"6","author":"Xu","year":"2018","journal-title":"Bone Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.bbrc.2005.05.132","article-title":"Bevacizumab (Avastin), a humanized anti-VEGF monoclonal antibody for cancer therapy","volume":"333","author":"Ferrara","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Lien, S., and Lowman, H. (2008). Therapeutic anti-VEGF antibodies. Therapeutic Antibodies, Springer.","DOI":"10.1007\/978-3-540-73259-4_6"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"R178","DOI":"10.1186\/ar3142","article-title":"Intravenous administration of anti-vascular endothelial growth factor humanized monoclonal antibody bevacizumab improves articular cartilage repair","volume":"12","author":"Nagai","year":"2010","journal-title":"Arthritis Res. Ther."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1177\/03635465211005102","article-title":"Intra-articular injection of bevacizumab enhances bone marrow stimulation\u2013mediated cartilage repair in a rabbit osteochondral defect model","volume":"49","author":"Utsunomiya","year":"2021","journal-title":"Am. J. Sports Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1016\/j.joca.2006.04.004","article-title":"Microfracture and bone morphogenetic protein 7 (BMP-7) synergistically stimulate articular cartilage repair","volume":"14","author":"Kuo","year":"2006","journal-title":"Osteoarthr. Cartil."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1089\/ten.tea.2010.0540","article-title":"Hyaline cartilage regeneration by combined therapy of microfracture and long-term bone morphogenetic protein-2 delivery","volume":"17","author":"Yang","year":"2011","journal-title":"Tissue Eng. Part A"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Kumari, R., and Jat, P. (2021). Mechanisms of cellular senescence: Cell cycle arrest and senescence associated secretory phenotype. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.645593"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1111\/cas.13184","article-title":"Impact of senescence-associated secretory phenotype and its potential as a therapeutic target for senescence-associated diseases","volume":"108","author":"Watanabe","year":"2017","journal-title":"Cancer Sci."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/s41584-020-00533-7","article-title":"Mechanisms and therapeutic implications of cellular senescence in osteoarthritis","volume":"17","author":"Coryell","year":"2021","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"101249","DOI":"10.1016\/j.arr.2020.101249","article-title":"The role of metabolism in chondrocyte dysfunction and the progression of osteoarthritis","volume":"66","author":"Zheng","year":"2021","journal-title":"Ageing Res. Rev."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/nrrheum.2016.65","article-title":"Ageing and the pathogenesis of osteoarthritis","volume":"12","author":"Loeser","year":"2016","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Huard, C.A., Gao, X., Dey Hazra, M.E., Dey Hazra, R.-O., Lebsock, K., Easley, J.T., Millett, P.J., and Huard, J. (2023). Effects of Fisetin treatment on cellular senescence of various tissues and organs of old sheep. Antioxidants, 12.","DOI":"10.20944\/preprints202306.1922.v1"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"955","DOI":"10.18632\/aging.101202","article-title":"New agents that target senescent cells: The flavone, fisetin, and the BCL-XL inhibitors, A1331852 and A1155463","volume":"9","author":"Zhu","year":"2017","journal-title":"Aging"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/2325967121S00604","article-title":"Paper 40: Improved Cartilage Healing with Microfracture Augmented with Fisetin & Bone Marrow Aspirate Concentrate in Acute Osteochondral Defect","volume":"10","author":"Gao","year":"2022","journal-title":"Orthop. J. Sports Med."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1177\/0963689717723636","article-title":"Exosomes and stem cells in degenerative disease diagnosis and therapy","volume":"27","author":"Chang","year":"2018","journal-title":"Cell Transplant."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/s13287-018-0791-7","article-title":"Mesenchymal stem cell-derived extracellular vesicles: Novel frontiers in regenerative medicine","volume":"9","author":"Keshtkar","year":"2018","journal-title":"Stem Cell Res. Ther."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"2318","DOI":"10.1016\/j.biopha.2018.11.099","article-title":"Mesenchymal stem cell-based therapy of osteoarthritis: Current knowledge and future perspectives","volume":"109","author":"Harrell","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.1016\/j.biocel.2012.08.007","article-title":"Exosomes: New players in cell\u2013cell communication","volume":"44","author":"Bang","year":"2012","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Alzahrani, F.A., and Saadeldin, I.M. (2021). Role of Exosomes in Biological Communication Systems, Springer.","DOI":"10.1007\/978-981-15-6599-1"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1800149","DOI":"10.1002\/pmic.201800149","article-title":"Exosomes in inflammation and inflammatory disease","volume":"19","author":"Chan","year":"2019","journal-title":"Proteomics"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.cca.2018.11.009","article-title":"Exosomes in inflammation and role as biomarkers","volume":"488","author":"Console","year":"2019","journal-title":"Clin. Chim. Acta"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"eaau6977","DOI":"10.1126\/science.aau6977","article-title":"The biology, function, and biomedical applications of exosomes","volume":"367","author":"Kalluri","year":"2020","journal-title":"Science"},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Aheget, H., Mazini, L., Martin, F., Belqat, B., Marchal, J.A., and Benabdellah, K. (2020). Exosomes: Their role in pathogenesis, diagnosis and treatment of diseases. Cancers, 13.","DOI":"10.3390\/cancers13010084"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"3477","DOI":"10.1038\/ncomms4477","article-title":"Syntenin-ALIX exosome biogenesis and budding into multivesicular bodies are controlled by ARF6 and PLD2","volume":"5","author":"Ghossoub","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1002\/jcb.22733","article-title":"Visualizing of the cellular uptake and intracellular trafficking of exosomes by live-cell microscopy","volume":"111","author":"Tian","year":"2010","journal-title":"J. Cell. Biochem."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1186\/s13045-020-00987-y","article-title":"Isolation and characterization of exosomes for cancer research","volume":"13","author":"Zhu","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1007\/s00018-019-03071-y","article-title":"Extracellular vesicle isolation methods: Rising impact of size-exclusion chromatography","volume":"76","author":"Roura","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1158\/1541-7786.MCR-18-0891","article-title":"Internalization of exosomes through receptor-mediated endocytosis","volume":"17","author":"Gonda","year":"2019","journal-title":"Mol. Cancer Res."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1016\/j.jprot.2010.06.006","article-title":"Exosomes: Extracellular organelles important in intercellular communication","volume":"73","author":"Mathivanan","year":"2010","journal-title":"J. Proteom."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"5338","DOI":"10.3390\/ijms14035338","article-title":"Exosomes as intercellular signaling organelles involved in health and disease: Basic science and clinical applications","volume":"14","author":"Corrado","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.biocel.2011.10.005","article-title":"Exosomes: Small vesicles participating in intercellular communication","volume":"44","author":"Ludwig","year":"2012","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"2103222","DOI":"10.1002\/advs.202103222","article-title":"Exosome processing and characterization approaches for research and technology development","volume":"9","author":"Lai","year":"2022","journal-title":"Adv. Sci."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"eaav8521","DOI":"10.1126\/scitranslmed.aav8521","article-title":"Advances in therapeutic applications of extracellular vesicles","volume":"11","author":"Wiklander","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.7150\/ijms.52768","article-title":"Subpopulations of exosomes purified via different exosomal markers carry different microRNA contents","volume":"18","author":"Wu","year":"2021","journal-title":"Int. J. Med. Sci."},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Zhou, Q., Cai, Y., Jiang, Y., and Lin, X. (2020). Exosomes in osteoarthritis and cartilage injury: Advanced development and potential therapeutic strategies. Int. J. Biol. Sci., 16.","DOI":"10.7150\/ijbs.41637"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nrm.2017.125","article-title":"Shedding light on the cell biology of extracellular vesicles","volume":"19","author":"Raposo","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/15330338211041203","article-title":"Diagnostic and therapeutic potential of extracellular vesicles","volume":"20","author":"Kodam","year":"2021","journal-title":"Technol. Cancer Res. Treat."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1038\/cr.2015.39","article-title":"Resolving sorting mechanisms into exosomes","volume":"25","author":"Stoorvogel","year":"2015","journal-title":"Cell Res."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/0963689720968495","article-title":"Compositional variation and functional mechanism of exosomes in the articular microenvironment in knee osteoarthritis","volume":"29","author":"Li","year":"2020","journal-title":"Cell Transplant."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Mosquera-Heredia, M.I., Morales, L.C., Vidal, O.M., Barcelo, E., Silvera-Redondo, C., V\u00e9lez, J.I., and Garavito-Galofre, P. (2021). Exosomes: Potential disease biomarkers and new therapeutic targets. Biomedicines, 9.","DOI":"10.3390\/biomedicines9081061"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"3257","DOI":"10.1182\/blood-2004-03-0824","article-title":"Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells","volume":"104","author":"Morelli","year":"2004","journal-title":"Blood"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1111\/j.1600-0854.2004.00223.x","article-title":"Exosome secretion: The art of reutilizing nonrecycled proteins?","volume":"5","author":"Hoekstra","year":"2004","journal-title":"Traffic"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"14402","DOI":"10.1021\/acs.analchem.8b03959","article-title":"ExoAPP: Exosome-oriented, aptamer nanoprobe-enabled surface proteins profiling and detection","volume":"90","author":"Jin","year":"2018","journal-title":"Anal. Chem."},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Bunggulawa, E.J., Wang, W., Yin, T., Wang, N., Durkan, C., Wang, Y., and Wang, G. (2018). Recent advancements in the use of exosomes as drug delivery systems. J. Nanobiotechnol., 16.","DOI":"10.1186\/s12951-018-0403-9"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.reth.2020.07.007","article-title":"Degenerative osteoarthritis a reversible chronic disease","volume":"15","year":"2020","journal-title":"Regen. Ther."},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Alcaraz, M.J., Compa\u00f1, A., and Guill\u00e9n, M.I. (2019). Extracellular vesicles from mesenchymal stem cells as novel treatments for musculoskeletal diseases. Cells, 9.","DOI":"10.3390\/cells9010098"},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Fan, W.-J., Liu, D., Pan, L.-Y., Wang, W.-Y., Ding, Y.-L., Zhang, Y.-Y., Ye, R.-X., Zhou, Y., An, S.-B., and Xiao, W.-F. (2022). Exosomes in osteoarthritis: Updated insights on pathogenesis, diagnosis, and treatment. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.949690"},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Butreddy, A., Kommineni, N., and Dudhipala, N. (2021). Exosomes as naturally occurring vehicles for delivery of biopharmaceuticals: Insights from drug delivery to clinical perspectives. Nanomaterials, 11.","DOI":"10.3390\/nano11061481"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.apsb.2016.02.001","article-title":"Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes: Current perspectives and future challenges","volume":"6","author":"Ha","year":"2016","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_153","first-page":"1525","article-title":"Exosome mimetics: A novel class of drug delivery systems","volume":"7","author":"Kooijmans","year":"2012","journal-title":"Int. J. Nanomed."},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Rodeo, S.A. (2023). Exosomes: The New Kid on the Block in Orthobiologics, SAGE Publications.","DOI":"10.1177\/03635465231207060"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1186\/s13018-019-1529-7","article-title":"Exosomes derived from platelet-rich plasma present a novel potential in alleviating knee osteoarthritis by promoting proliferation and inhibiting apoptosis of chondrocyte via Wnt\/\u03b2-catenin signaling pathway","volume":"14","author":"Liu","year":"2019","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"733","DOI":"10.7150\/thno.17450","article-title":"Exosomes derived from human platelet-rich plasma prevent apoptosis induced by glucocorticoid-associated endoplasmic reticulum stress in rat osteonecrosis of the femoral head via the Akt\/Bad\/Bcl-2 signal pathway","volume":"7","author":"Tao","year":"2017","journal-title":"Theranostics"},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Wang, X., Chen, J., Qian, D., Gao, P., Qin, T., Jiang, T., Yi, J., Xu, T., and Huang, Y. (2022). Exosomes derived from platelet-rich plasma administration in site mediate cartilage protection in subtalar osteoarthritis. J. Nanobiotechnol., 20.","DOI":"10.1186\/s12951-022-01245-8"},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Khayambashi, P., Iyer, J., Pillai, S., Upadhyay, A., Zhang, Y., and Tran, S.D. (2021). Hydrogel encapsulation of mesenchymal stem cells and their derived exosomes for tissue engineering. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22020684"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"18472","DOI":"10.1021\/acsami.0c22671","article-title":"Umbilical mesenchymal stem cell-derived exosome-encapsulated hydrogels accelerate bone repair by enhancing angiogenesis","volume":"13","author":"Zhang","year":"2021","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"2101741","DOI":"10.1002\/smll.202101741","article-title":"Bone-a-petite: Engineering exosomes towards bone, osteochondral, and cartilage repair","volume":"17","author":"Bei","year":"2021","journal-title":"Small"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"8740","DOI":"10.1039\/D1NR01314A","article-title":"Cell-free exosome-laden scaffolds for tissue repair","volume":"13","author":"Huang","year":"2021","journal-title":"Nanoscale"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1902\/jop.2003.74.6.849","article-title":"Platelet-rich plasma contains high levels of platelet-derived growth factor and transforming growth factor-\u03b2 and modulates the proliferation of periodontally related cells in vitro","volume":"74","author":"Okuda","year":"2003","journal-title":"J. Periodontol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1097\/JSA.0b013e3182999712","article-title":"The basic science of platelet-rich plasma (PRP): What clinicians need to know","volume":"21","author":"Arnoczky","year":"2013","journal-title":"Sports Med. Arthrosc. Rev."},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"B\u00f6rger, V., Bremer, M., Ferrer-Tur, R., Gockeln, L., Stambouli, O., Becic, A., and Giebel, B. (2017). Mesenchymal stem\/stromal cell-derived extracellular vesicles and their potential as novel immunomodulatory therapeutic agents. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18071450"},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Ferreira, J.R., Teixeira, G.Q., Santos, S.G., Barbosa, M.A., Almeida-Porada, G., and Gon\u00e7alves, R.M. (2018). Mesenchymal stromal cell secretome: Influencing therapeutic potential by cellular pre-conditioning. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02837"},{"key":"ref_166","doi-asserted-by":"crossref","unstructured":"Harrell, C.R., Fellabaum, C., Jovicic, N., Djonov, V., Arsenijevic, N., and Volarevic, V. (2019). Molecular mechanisms responsible for therapeutic potential of mesenchymal stem cell-derived secretome. Cells, 8.","DOI":"10.3390\/cells8050467"},{"key":"ref_167","first-page":"6275","article-title":"Mesenchymal stem cell related therapies for cartilage lesions and osteoarthritis","volume":"11","author":"Zhang","year":"2019","journal-title":"Am. J. Transl. Res."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1002\/stem.2575","article-title":"Concise review: MSC-derived exosomes for cell-free therapy","volume":"35","author":"Phinney","year":"2017","journal-title":"Stem Cells"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/s41536-019-0083-6","article-title":"Mesenchymal stem cell perspective: Cell biology to clinical progress","volume":"4","author":"Pittenger","year":"2019","journal-title":"NPJ Regen. Med."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1002\/jcb.22399","article-title":"Bone marrow mesenchymal stem cells","volume":"109","author":"Ohishi","year":"2010","journal-title":"J. Cell. Biochem."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.jcyt.2015.10.008","article-title":"The current landscape of the mesenchymal stromal cell secretome: A new paradigm for cell-free regeneration","volume":"18","author":"Konala","year":"2016","journal-title":"Cytotherapy"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"2771","DOI":"10.1007\/s00018-020-03454-6","article-title":"Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy","volume":"77","author":"Fan","year":"2020","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1093\/rheumatology\/kem206","article-title":"Human bone marrow mesenchymal stem cells in vivo","volume":"47","author":"Jones","year":"2008","journal-title":"Rheumatology"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1089\/hum.2010.115","article-title":"Bone marrow mesenchymal stem cells: Historical overview and concepts","volume":"21","author":"Charbord","year":"2010","journal-title":"Hum. Gene Ther."},{"key":"ref_175","doi-asserted-by":"crossref","unstructured":"Harrell, C.R., Jovicic, N., Djonov, V., Arsenijevic, N., and Volarevic, V. (2019). Mesenchymal stem cell-derived exosomes and other extracellular vesicles as new remedies in the therapy of inflammatory diseases. Cells, 8.","DOI":"10.3390\/cells8121605"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.amjms.2020.07.025","article-title":"Human bone marrow mesenchymal stem cell-derived exosomes attenuate IL-1\u03b2-induced annulus fibrosus cell damage","volume":"360","author":"Li","year":"2020","journal-title":"Am. J. Med. Sci."},{"key":"ref_177","doi-asserted-by":"crossref","unstructured":"Cosenza, S., Ruiz, M., Toupet, K., Jorgensen, C., and No\u00ebl, D. (2017). Mesenchymal stem cells derived exosomes and microparticles protect cartilage and bone from degradation in osteoarthritis. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-15376-8"},{"key":"ref_178","doi-asserted-by":"crossref","unstructured":"Yano, F., Ohba, S., Murahashi, Y., Tanaka, S., Saito, T., and Chung, U.-I. (2019). Runx1 contributes to articular cartilage maintenance by enhancement of cartilage matrix production and suppression of hypertrophic differentiation. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-43948-3"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/s41413-022-00231-y","article-title":"Runx1 is a key regulator of articular cartilage homeostasis by orchestrating YAP, TGF\u03b2, and Wnt signaling in articular cartilage formation and osteoarthritis","volume":"10","author":"Zhang","year":"2022","journal-title":"Bone Res."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"9281","DOI":"10.1111\/jcmm.16860","article-title":"Therapeutic effects of bone marrow mesenchymal stem cells-derived exosomes on osteoarthritis","volume":"25","author":"Jin","year":"2021","journal-title":"J. Cell. Mol. Med."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/s13287-017-0563-9","article-title":"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","volume":"8","author":"Lu","year":"2017","journal-title":"Stem Cell Res. Ther."},{"key":"ref_182","doi-asserted-by":"crossref","unstructured":"Zhang, X., Wang, W., Zhu, W., Dong, J., Cheng, Y., Yin, Z., and Shen, F. (2019). Mechanisms and functions of long non-coding RNAs at multiple regulatory levels. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20225573"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/nrm2347","article-title":"Small non-coding RNAs in animal development","volume":"9","author":"Stefani","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_184","unstructured":"Velez, C. (2023). Unraveling the Mystery of Non-Coding Genomic Content: Evolution, Regulation, and Functional Significance. [Master\u2019s Thesis, SUNY Downstate Health Sciences University]."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1186\/s13287-015-0116-z","article-title":"Human bone marrow-and adipose-mesenchymal stem cells secrete exosomes enriched in distinctive miRNA and tRNA species","volume":"6","author":"Baglio","year":"2015","journal-title":"Stem Cell Res. Ther."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1186\/s12964-020-00650-6","article-title":"Exosomal microRNAs derived from mesenchymal stem cells: Cell-to-cell messages","volume":"18","author":"Asgarpour","year":"2020","journal-title":"Cell Commun. Signal."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"3930","DOI":"10.1096\/fj.13-249318","article-title":"MicroRNA-1 regulates chondrocyte phenotype by repressing histone deacetylase 4 during growth plate development","volume":"28","author":"Li","year":"2014","journal-title":"FASEB J."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1016\/j.omtn.2020.09.014","article-title":"Synovial mesenchymal stem cell-derived EV-packaged miR-31 downregulates histone demethylase KDM2A to prevent knee osteoarthritis","volume":"22","author":"Wang","year":"2020","journal-title":"Mol. Ther.-Nucleic Acids"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"4877","DOI":"10.3892\/mmr.2015.4008","article-title":"Presence and function of microRNA-92a in chondrogenic ATDC5 and adipose-derived mesenchymal stem cells","volume":"12","author":"Hou","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1186\/s13287-018-1004-0","article-title":"Exosomes derived from miR-92a-3p-overexpressing human mesenchymal stem cells enhance chondrogenesis and suppress cartilage degradation via targeting WNT5A","volume":"9","author":"Mao","year":"2018","journal-title":"Stem Cell Res. Ther."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"5354","DOI":"10.1111\/jcmm.13808","article-title":"Exosomal miR-95-5p regulates chondrogenesis and cartilage degradation via histone deacetylase 2\/8","volume":"22","author":"Mao","year":"2018","journal-title":"J. Cell. Mol. Med."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.biomaterials.2019.03.022","article-title":"miR-100-5p-abundant exosomes derived from infrapatellar fat pad MSCs protect articular cartilage and ameliorate gait abnormalities via inhibition of mTOR in osteoarthritis","volume":"206","author":"Wu","year":"2019","journal-title":"Biomaterials"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"2756","DOI":"10.1080\/15384101.2018.1556063","article-title":"TGF-\u03b21 promoted chondrocyte proliferation by regulating Sp1 through MSC-exosomes derived miR-135b","volume":"17","author":"Wang","year":"2018","journal-title":"Cell Cycle"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"180","DOI":"10.7150\/thno.17133","article-title":"Exosomes derived from miR-140-5p-overexpressing human synovial mesenchymal stem cells enhance cartilage tissue regeneration and prevent osteoarthritis of the knee in a rat model","volume":"7","author":"Tao","year":"2017","journal-title":"Theranostics"},{"key":"ref_195","first-page":"1881","article-title":"Exosomes from adipose-derived stem cells promote chondrogenesis and suppress inflammation by upregulating miR-145 and miR-221","volume":"21","author":"Zhao","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s10565-020-09559-9","article-title":"Exosomes derived from miR-155-5p\u2013overexpressing synovial mesenchymal stem cells prevent osteoarthritis via enhancing proliferation and migration, attenuating apoptosis, and modulating extracellular matrix secretion in chondrocytes","volume":"37","author":"Wang","year":"2021","journal-title":"Cell Biol. Toxicol."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1016\/j.joca.2015.12.012","article-title":"MicroRNA-320 regulates matrix metalloproteinase-13 expression in chondrogenesis and interleukin-1\u03b2-induced chondrocyte responses","volume":"24","author":"Meng","year":"2016","journal-title":"Osteoarthr. Cartil."},{"key":"ref_198","first-page":"502","article-title":"miR-486-5p is upregulated in osteoarthritis and inhibits chondrocyte proliferation and migration by suppressing SMAD2","volume":"18","author":"Shi","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"S108","DOI":"10.21037\/atm.2019.05.11","article-title":"Microfracture for cartilage repair in the knee: Current concepts and limitations of systematic reviews","volume":"7","author":"Song","year":"2019","journal-title":"Ann. Transl. Med."},{"key":"ref_200","doi-asserted-by":"crossref","unstructured":"Budhiparama, N.C., Putramega, D., and Lumban-Gaol, I. (2024). Orthobiologics in knee osteoarthritis, dream or reality?. Arch. Orthop. Trauma Surg.","DOI":"10.1007\/s00402-024-05310-9"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"S311","DOI":"10.1098\/rsif.2008.0448.focus","article-title":"Biomaterial technology for tissue engineering applications","volume":"6","author":"Tabata","year":"2009","journal-title":"J. R. Soc. Interface"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/S1369-7021(11)70058-X","article-title":"Biomaterials & scaffolds for tissue engineering","volume":"14","year":"2011","journal-title":"Mater. Today"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1615\/CritRevEukaryotGeneExpr.2018024574","article-title":"The use of scaffolds in cartilage regeneration","volume":"28","author":"Kalkan","year":"2018","journal-title":"Crit. Rev.\u2122 Eukaryot. Gene Expr."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"290602","DOI":"10.1155\/2011\/290602","article-title":"Polymeric scaffolds in tissue engineering application: A review","volume":"2011","author":"Dhandayuthapani","year":"2011","journal-title":"Int. J. Polym. Sci."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"28p","DOI":"10.1615\/CritRevEukarGeneExpr.v12.i3.40","article-title":"Scaffolds for tissue engineering of cartilage","volume":"12","author":"Woodfield","year":"2002","journal-title":"Crit. Rev.\u2122 Eukaryot. Gene Expr."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.tibtech.2004.05.005","article-title":"Scaffold-based tissue engineering: Rationale for computer-aided design and solid free-form fabrication systems","volume":"22","author":"Hutmacher","year":"2004","journal-title":"Trends Biotechnol."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1089\/ten.tec.2009.0444","article-title":"Fabrication and repair of cartilage defects with a novel acellular cartilage matrix scaffold","volume":"16","author":"Yang","year":"2010","journal-title":"Tissue Eng. Part C Methods"},{"key":"ref_208","doi-asserted-by":"crossref","unstructured":"Jia, L., Zhang, P., Ci, Z., Hao, X., Bai, B., Zhang, W., Jiang, H., and Zhou, G. (2022). Acellular cartilage matrix biomimetic scaffold with immediate enrichment of autologous bone marrow mononuclear cells to repair articular cartilage defects. Mater. Today Bio, 15.","DOI":"10.1016\/j.mtbio.2022.100310"},{"key":"ref_209","doi-asserted-by":"crossref","unstructured":"Wang, Y., Xu, Y., Zhou, G., Liu, Y., and Cao, Y. (2021). Biological evaluation of acellular cartilaginous and dermal matrixes as tissue engineering scaffolds for cartilage regeneration. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.624337"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"585","DOI":"10.3390\/cimb46010038","article-title":"Harnessing Natural Polymers for Nano-Scaffolds in Bone Tissue Engineering: A Comprehensive Overview of Bone Disease Treatment","volume":"46","author":"Saurav","year":"2024","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_211","first-page":"100180","article-title":"Acellular scaffolds, cellular therapy and next generation approaches for knee cartilage repair","volume":"4","author":"Debieux","year":"2024","journal-title":"J. Cartil. Jt. Preserv."},{"key":"ref_212","doi-asserted-by":"crossref","unstructured":"Demmer, W., Schinacher, J., Wiggenhauser, P.S., and Giunta, R.E. (2024). Use of Acellular Matrices as Scaffolds in Cartilage Regeneration: A Systematic Review. Adv. Wound Care.","DOI":"10.1089\/wound.2024.0065"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.mser.2007.12.001","article-title":"Advanced biomaterials for skeletal tissue regeneration: Instructive and smart functions","volume":"59","author":"Barrere","year":"2008","journal-title":"Mater. Sci. Eng. R Rep."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/1559325819892702","article-title":"Exosomes: A novel therapeutic agent for cartilage and bone tissue regeneration","volume":"17","author":"Liu","year":"2019","journal-title":"Dose-Response"},{"key":"ref_215","doi-asserted-by":"crossref","unstructured":"Benrashed, M.A., Alyousef, N.I., AlQahtani, N.H., AlMaimouni, Y.K., Khan, M., and Khan, A.S. (2022). Conventional to advanced endodontics: Use of bioactive materials. Biomaterials in Endodontics, Elsevier.","DOI":"10.1016\/B978-0-12-821746-7.00008-5"},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1007\/s10924-022-02615-x","article-title":"Preparation and in vitro osteogenic evaluation of biomimetic hybrid nanocomposite scaffolds based on gelatin\/plasma rich in growth factors (PRGF) and lithium-doped 45s5 bioactive glass nanoparticles","volume":"31","author":"Farmani","year":"2023","journal-title":"J. Polym. Environ."},{"key":"ref_217","first-page":"172","article-title":"Biological evaluation of bioceramic materials\u2014A review","volume":"24","author":"Thamaraiselvi","year":"2004","journal-title":"Carbon"},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"134168","DOI":"10.1016\/j.colsurfa.2024.134168","article-title":"Influence of lithium ion doping and mitoxantrone hydrochloride loading on the structure and in vitro biological properties of mesoporous bioactive glass microspheres in the treatment of multiple myeloma","volume":"695","author":"Zhang","year":"2024","journal-title":"Colloids Surf. A Physicochem. Eng. 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