{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T21:51:45Z","timestamp":1792014705930,"version":"4.4.0"},"reference-count":168,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,2,27]],"date-time":"2022-02-27T00:00:00Z","timestamp":1645920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Osteoarthritis (OA) is a prevalent and debilitating age-related joint disease characterized by articular cartilage degeneration, synovial membrane inflammation, osteophyte formation, as well as subchondral bone sclerosis. OA drugs at present are mainly palliative and do not halt or reverse disease progression. Currently, no disease-modifying OA drugs (DMOADs) are available and total joint arthroplasty remains a last resort. Therefore, there is an urgent need for the development of efficacious treatments for OA management. Among all novel pharmaco-therapeutical options, exosome-based therapeutic strategies are highly promising. Exosome cargoes, which include proteins, lipids, cytokines, and various RNA subtypes, are potentially capable of regulating intercellular communications and gene expression in target cells and tissues involved in OA development. With extensive research in recent years, exosomes in OA studies are no longer limited to classic, mesenchymal stem cell (MSC)-derived vesicles. New origins, structures, and functions of exosomes are constantly being discovered and investigated. This review systematically summarizes the non-classic origins, biosynthesis, and extraction of exosomes, describes modification and delivery techniques, explores their role in OA pathogenesis and progression, and discusses their therapeutic potential and hurdles to overcome in OA treatment.<\/jats:p>","DOI":"10.3390\/bioengineering9030099","type":"journal-article","created":{"date-parts":[[2022,2,27]],"date-time":"2022-02-27T20:46:17Z","timestamp":1645994777000},"page":"99","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Exosomes in the Pathogenesis, Progression, and Treatment of Osteoarthritis"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0909-2859","authenticated-orcid":false,"given":"Yishu","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6009-629X","authenticated-orcid":false,"given":"Zhong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA"},{"name":"Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3985-7779","authenticated-orcid":false,"given":"Yuchen","family":"He","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha 410008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"118602","DOI":"10.1016\/j.lfs.2020.118602","article-title":"Role of mitochondria in mediating chondrocyte response to mechanical stimuli","volume":"263","author":"He","year":"2020","journal-title":"Life Sci."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"He, Y., Li, Z., Alexander, P.G., Ocasio-Nieves, B.D., Yocum, L., Lin, H., and Tuan, R.S. (2020). Pathogenesis of osteoarthritis: Risk factors, regulatory pathways in chondrocytes, and experimental models. Biol., 9.","DOI":"10.3390\/biology9080194"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1016\/j.joca.2019.07.002","article-title":"Clinical, humanistic, and economic burden of osteoarthritis among noninstitutionalized adults in the United States","volume":"27","author":"Zhao","year":"2019","journal-title":"Osteoarthr. Cartil."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.joca.2020.10.006","article-title":"Osteoarthritis year in review 2020: Biology","volume":"29","author":"Bosch","year":"2021","journal-title":"Osteoarthr. Cartil."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.1093\/rheumatology\/kex287","article-title":"Infrapatellar fat pad features in osteoarthritis: A histopathological and molecular study","volume":"56","author":"Favero","year":"2017","journal-title":"Rheumatology (Oxford)"},{"key":"ref_6","first-page":"1659","article-title":"Incidence and risk factors for clinically diagnosed knee, hip and hand osteoarthritis: Influences of age, gender and osteoarthritis affecting other joints","volume":"73","author":"Judge","year":"2013","journal-title":"Ann. Rheum. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1097\/BOR.0000000000000479","article-title":"Epidemiology of osteoarthritis: Literature update","volume":"30","author":"Vina","year":"2018","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.bcp.2019.02.037","article-title":"Osteoarthritis phenotypes and novel therapeutic targets","volume":"165","author":"Kubassova","year":"2019","journal-title":"Biochem. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.mcna.2019.10.007","article-title":"Osteoarthritis: Pathology, diagnosis, and treatment options","volume":"104","author":"Abramoff","year":"2020","journal-title":"Med. Clin. N. Am."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1038\/s41584-020-00518-6","article-title":"Emerging pharmaceutical therapies for osteoarthritis","volume":"16","author":"Latourte","year":"2020","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1016\/S0140-6736(19)30417-9","article-title":"Osteoarthritis","volume":"393","author":"Hunter","year":"2019","journal-title":"Lancet"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Salgado, C., Jordan, O., and All\u00e9mann, E. (2021). Osteoarthritis in vitro models: Applications and implications in development of intra-articular drug delivery systems. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13010060"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3.22.1","DOI":"10.1002\/0471143030.cb0322s30","article-title":"Isolation and characterization of exosomes from cell culture supernatants and biological fluids","volume":"30","author":"Thery","year":"2006","journal-title":"Curr. Protoc. Cell Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"751079","DOI":"10.3389\/fcell.2021.751079","article-title":"Exosomes, a new star for targeted delivery","volume":"9","author":"Chen","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.2147\/IJN.S291956","article-title":"A comprehensive review on factors influences biogenesis, functions, therapeutic and clinical implications of exosomes","volume":"16","author":"Gurunathan","year":"2021","journal-title":"Int. J. Nanomed."},{"key":"ref_16","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_17","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_18","doi-asserted-by":"crossref","first-page":"10855","DOI":"10.1111\/jcmm.15714","article-title":"Curcumin reinforces MSC-derived exosomes in attenuating osteoarthritis via modulating the miR-124\/NF-kB and miR-143\/ROCK1\/TLR9 signalling pathways","volume":"24","author":"Qiu","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/s41413-020-0100-9","article-title":"Exosomes: Roles and therapeutic potential in osteoarthritis","volume":"8","author":"Ni","year":"2020","journal-title":"Bone Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/0005-2736(81)90512-5","article-title":"Exfoliation of membrane ecto-enzymes in the form of micro-vesicles","volume":"645","author":"Trams","year":"1981","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1016\/0092-8674(83)90040-5","article-title":"Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: Selective externalization of the receptor","volume":"33","author":"Pan","year":"1983","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"11973","DOI":"10.1021\/acsnano.0c05122","article-title":"Generation of small RNA-modulated exosome mimetics for bone regeneration","volume":"14","author":"Fan","year":"2020","journal-title":"ACS Nano"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6917","DOI":"10.2147\/IJN.S264498","article-title":"Exosome: A review of its classification, isolation techniques, storage, diagnostic and targeted therapy applications","volume":"15","author":"Zhang","year":"2020","journal-title":"Int. J. Nanomed."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"585","DOI":"10.2147\/IJN.S154458","article-title":"Engineered exosome-mediated delivery of functionally active miR-26a and its enhanced suppression effect in HepG2 cells","volume":"13","author":"Liang","year":"2018","journal-title":"Int. J. Nanomed."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.biomaterials.2016.09.031","article-title":"Exosome-based tumor antigens\u2013adjuvant co-delivery utilizing genetically engineered tumor cell-derived exosomes with immunostimulatory CpG DNA","volume":"111","author":"Morishita","year":"2016","journal-title":"Biomater."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1002\/art.34453","article-title":"Osteoarthritis: A disease of the joint as an organ","volume":"64","author":"Loeser","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Mustonen, A.-M., and Nieminen, P. (2021). Extracellular vesicles and their potential significance in the pathogenesis and treatment of osteoarthritis. Pharmaceuticals, 14.","DOI":"10.3390\/ph14040315"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Li, D., Gupta, P., Sgaglione, N., and Grande, D. (2021). Exosomes derived from non-classic sources for treatment of post-traumatic osteoarthritis and cartilage injury of the knee: In vivo review. J. Clin. Med., 10.","DOI":"10.3390\/jcm10092001"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4647","DOI":"10.18632\/aging.202506","article-title":"Vascular endothelial cell-secreted exosomes facilitate osteoarthritis pathogenesis by promoting chondrocyte apoptosis","volume":"13","author":"Yang","year":"2021","journal-title":"Aging (Albany NY)"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41419-019-1739-2","article-title":"The exosome-like vesicles from osteoarthritic chondrocyte enhanced mature IL-1\u03b2 production of macrophages and aggravated synovitis in osteoarthritis","volume":"10","author":"Ni","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3193","DOI":"10.2217\/nnm-2018-0498","article-title":"Primary chondrocyte exosomes mediate osteoarthritis progression by regulating mitochondrion and immune reactivity","volume":"14","author":"Zheng","year":"2019","journal-title":"Nanomedicine (Lond)"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Wu, X., Crawford, R., Xiao, Y., Mao, X., and Prasadam, I. (2021). Osteoarthritic subchondral bone release exosomes that promote cartilage degeneration. Cells, 10.","DOI":"10.3390\/cells10020251"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2411","DOI":"10.1080\/15384101.2018.1526603","article-title":"MSC-derived exosomes promote proliferation and inhibit apoptosis of chondrocytes via lncRNA-KLF3-AS1\/miR-206\/GIT1 axis in osteoarthritis","volume":"17","author":"Liu","year":"2018","journal-title":"Cell Cycle"},{"key":"ref_34","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_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-017-15376-8","article-title":"Mesenchymal stem cells derived exosomes and microparticles protect cartilage and bone from degradation in osteoarthritis","volume":"7","author":"Cosenza","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2439","DOI":"10.7150\/thno.31017","article-title":"Desktop-stereolithography 3D printing of a radially oriented extracellular matrix\/mesenchymal stem cell exosome bioink for osteochondral defect regeneration","volume":"9","author":"Chen","year":"2019","journal-title":"Theranostics"},{"key":"ref_37","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_38","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_39","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.biomaterials.2019.02.006","article-title":"MSC exosomes alleviate temporomandibular joint osteoarthritis by attenuating inflammation and restoring matrix homeostasis","volume":"200","author":"Zhang","year":"2019","journal-title":"Biomaterials"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13287-017-0632-0","article-title":"Exosomes from embryonic mesenchymal stem cells alleviate osteoarthritis through balancing synthesis and degradation of cartilage extracellular matrix","volume":"8","author":"Wang","year":"2017","journal-title":"Stem Cell Res. Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s13287-017-0510-9","article-title":"Comparison of exosomes secreted by induced pluripotent stem cell-derived mesenchymal stem cells and synovial membrane-derived mesenchymal stem cells for the treatment of osteoarthritis","volume":"8","author":"Zhu","year":"2017","journal-title":"Stem Cell Res. Ther."},{"key":"ref_42","first-page":"111","article-title":"Exosomes derived from umbilical cord mesenchymal stem cells in mechanical environment show improved osteochondral activity via upregulation of LncRNA H19","volume":"26","author":"Yan","year":"2021","journal-title":"J. Orthop. Transl."},{"key":"ref_43","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_44","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_45","doi-asserted-by":"crossref","first-page":"1735249","DOI":"10.1080\/20013078.2020.1735249","article-title":"Small extracellular vesicles from human adipose-derived stem cells attenuate cartilage degeneration","volume":"9","author":"Woo","year":"2020","journal-title":"J. Extracell. Vesicles"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1002\/biof.1576","article-title":"Comparison of the therapeutic effect of amniotic fluid stem cells and their exosomes on monoiodoacetate-induced animal model of osteoarthritis","volume":"46","author":"Zavatti","year":"2020","journal-title":"BioFactors"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"36938","DOI":"10.1021\/acsami.0c10458","article-title":"Chondrocyte-targeted microRNA delivery by engineered exosomes toward a cell-free osteoarthritis therapy","volume":"12","author":"Liang","year":"2020","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s13287-020-01594-x","article-title":"Intra-articular delivery of extracellular vesicles secreted by chondrogenic progenitor cells from MRL\/MpJ superhealer mice enhances articular cartilage repair in a mouse injury model","volume":"11","author":"Wang","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_49","first-page":"1","article-title":"Fibroblast-like synoviocytes-derived exosomal PCGEM1 accelerates IL-1\u03b2-induced apoptosis and cartilage matrix degradation by miR-142-5p\/RUNX2 in chondrocytes","volume":"10","author":"Zeng","year":"2021","journal-title":"Immunol. Investig."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/s41420-021-00418-y","article-title":"Exosomes derived from miR-126-3p-overexpressing synovial fibroblasts suppress chondrocyte inflammation and cartilage degradation in a rat model of osteoarthritis","volume":"7","author":"Zhou","year":"2021","journal-title":"Cell Death Discov."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"584050","DOI":"10.3389\/fbioe.2020.584050","article-title":"Characterization and chondroprotective effects of extracellular vesicles from plasma- and serum-based autologous blood-derived products for osteoarthritis therapy","volume":"8","author":"Otahal","year":"2020","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5475","DOI":"10.1111\/jcmm.14430","article-title":"Exosomes from tendon stem cells promote injury tendon healing through balancing synthesis and degradation of the tendon extracellular matrix","volume":"23","author":"Wang","year":"2019","journal-title":"J. Cell. Mol. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s10616-018-0264-y","article-title":"Tenocyte-derived exosomes induce the tenogenic differentiation of mesenchymal stem cells through TGF-\u03b2","volume":"71","author":"Xu","year":"2019","journal-title":"Cytotechnology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.3389\/fimmu.2019.01310","article-title":"Cyclic stretch force induces periodontal ligament cells to secrete exosomes that suppress IL-1\u03b2 production through the inhibition of the NF-\u03baB signaling pathway in macrophages","volume":"10","author":"Wang","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.archoralbio.2019.06.002","article-title":"Periodontal ligament fibroblasts regulate osteoblasts by exosome secretion induced by inflammatory stimuli","volume":"105","author":"Zhao","year":"2019","journal-title":"Arch. Oral Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"105263","DOI":"10.1016\/j.archoralbio.2021.105263","article-title":"Periodontal ligament fibroblast-derived exosomes induced by compressive force promote macrophage M1 polarization via Yes-associated protein","volume":"132","author":"Zhao","year":"2021","journal-title":"Arch. Oral Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1007\/s00167-018-5118-9","article-title":"Injective mesenchymal stem cell-based treatments for knee osteoarthritis: From mechanisms of action to current clinical evidences","volume":"27","author":"Lopa","year":"2019","journal-title":"Knee Surg. Sports Traumatol. Arthrosc."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"768771","DOI":"10.3389\/fimmu.2021.768771","article-title":"Role of microRNA shuttled in small extracellular vesicles derived from mesenchymal stem\/stromal cells for osteoarticular disease treatment","volume":"12","author":"Araya","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.biomaterials.2017.11.028","article-title":"MSC exosomes mediate cartilage repair by enhancing proliferation, attenuating apoptosis and modulating immune reactivity","volume":"156","author":"Zhang","year":"2018","journal-title":"Biomaterials"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1517\/14712598.2016.1131976","article-title":"Exosomes for repair, regeneration and rejuvenation","volume":"16","author":"Basu","year":"2016","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.3892\/ijmm.2015.2114","article-title":"Integrin-\u03b21 regulates chondrocyte proliferation and apoptosis through the upregulation of GIT1 expression","volume":"35","author":"Zhang","year":"2015","journal-title":"Int. J. Mol. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"7197598","DOI":"10.1155\/2017\/7197598","article-title":"Extracellular vesicles from adipose-derived mesenchymal stem cells downregulate senescence features in osteoarthritic osteoblasts","volume":"2017","author":"Alcaraz","year":"2017","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1089\/scd.2021.0010","article-title":"Anti-inflammatory effects of conditioned medium of periodontal ligament-derived stem cells on chondrocytes, synoviocytes, and meniscus cells","volume":"30","author":"Huang","year":"2021","journal-title":"Stem Cells Dev."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"6624874","DOI":"10.1155\/2021\/6624874","article-title":"Exosomes from kartogenin-pretreated infrapatellar fat pad mesenchymal stem cells enhance chondrocyte anabolism and articular cartilage regeneration","volume":"2021","author":"Shao","year":"2021","journal-title":"Stem Cells Int."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"179","DOI":"10.5792\/ksrr.17.061","article-title":"Infrapatellar fat pad-derived stem cell-based regenerative strategies in orthopedic surgery","volume":"30","author":"Huri","year":"2018","journal-title":"Knee Surg. Relat. Res."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Lin, J., Wang, L., Lin, J., and Liu, Q. (2021). The role of extracellular vesicles in the pathogenesis, diagnosis, and treatment of osteoarthritis. Molecules, 26.","DOI":"10.3390\/molecules26164987"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.bone.2015.05.013","article-title":"Matrix vesicles: Are they anchored exosomes?","volume":"79","author":"Shapiro","year":"2015","journal-title":"Bone"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.bbrc.2009.08.038","article-title":"Articular cartilage vesicles contain RNA","volume":"388","author":"Mitton","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.bbrc.2019.12.065","article-title":"Chondrocytes-derived exosomal miR-8485 regulated the Wnt\/\u03b2-catenin pathways to promote chondrogenic differentiation of BMSCs","volume":"523","author":"Li","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.stem.2009.01.015","article-title":"Migratory chondrogenic progenitor cells from repair tissue during the later stages of human osteoarthritis","volume":"4","author":"Koelling","year":"2009","journal-title":"Cell Stem Cell"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"R163","DOI":"10.1186\/ar4679","article-title":"Exosomes from IL-1\u03b2 stimulated synovial fibroblasts induce osteoarthritic changes in articular chondrocytes","volume":"16","author":"Kato","year":"2014","journal-title":"Arthritis Res. Ther."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13075-017-1229-9","article-title":"Synovitis in osteoarthritis: Current understanding with therapeutic implications","volume":"19","author":"Mathiessen","year":"2017","journal-title":"Arthritis Res. Ther."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1002\/prca.201500064","article-title":"Effects of methotrexate and salazosulfapyridine on protein profiles of exosomes derived from a human synovial sarcoma cell line of SW982","volume":"10","author":"Tsuno","year":"2015","journal-title":"Proteom. Clin. Appl."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1007\/s10753-020-01227-8","article-title":"The fibroblast-like synoviocyte derived exosomal long non-coding RNA H19 alleviates osteoarthritis progression through the miR-106b-5p\/TIMP2 axis","volume":"43","author":"Tan","year":"2020","journal-title":"Inflammation"},{"key":"ref_75","first-page":"261","article-title":"Macrophages in osteoarthritis: Pathophysiology and therapeutics","volume":"12","author":"Chen","year":"2020","journal-title":"Am J Transl Res"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13075-015-0735-x","article-title":"A systematic review of the relationship between subchondral bone features, pain and structural pathology in peripheral joint osteoarthritis","volume":"17","author":"Barr","year":"2015","journal-title":"Arthritis Res. Ther."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"223","DOI":"10.3892\/br.2016.824","article-title":"Circulating osteocyte-derived exosomes contain miRNAs which are enriched in exosomes from MLO-Y4 cells","volume":"6","author":"Sato","year":"2017","journal-title":"Biomed. Rep."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13287-020-01815-3","article-title":"Osteocyte-derived exosomes induced by mechanical strain promote human periodontal ligament stem cell proliferation and osteogenic differentiation via the miR-181b-5p\/PTEN\/AKT signaling pathway","volume":"11","author":"Lv","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"11021","DOI":"10.1074\/jbc.M116.770941","article-title":"Myostatin inhibits osteoblastic differentiation by suppressing osteocyte-derived exosomal microRNA-218: A novel mechanism in muscle-bone communication","volume":"292","author":"Qin","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"111301","DOI":"10.1016\/j.mce.2021.111301","article-title":"Osteocyte exosomes accelerate benign prostatic hyperplasia development","volume":"531","author":"Wang","year":"2021","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1016\/j.joca.2018.03.004","article-title":"Systemic and local adipose tissue in knee osteoarthritis","volume":"26","author":"Chang","year":"2018","journal-title":"Osteoarthr. Cartil."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1007\/s10930-015-9616-z","article-title":"Proteomic analysis of extracellular vesicles released by adipocytes of Otsuka Long-Evans Tokushima fatty (OLETF) rats","volume":"34","author":"Lee","year":"2015","journal-title":"J. Protein Chem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.bbrc.2014.01.183","article-title":"Lipid synthesis is promoted by hypoxic adipocyte-derived exosomes in 3T3-L1 cells","volume":"445","author":"Sano","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"4041","DOI":"10.1172\/JCI129193","article-title":"Interorgan communication by exosomes, adipose tissue, and adiponectin in metabolic syndrome","volume":"129","author":"Kita","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e007442","DOI":"10.1161\/JAHA.117.007442","article-title":"Adipose-derived exosomes exert proatherogenic effects by regulating macrophage foam cell formation and polarization","volume":"7","author":"Xie","year":"2018","journal-title":"J. Am. Hear. Assoc."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.2337\/db09-0216","article-title":"Adipose tissue exosome-like vesicles mediate activation of macrophage-induced insulin resistance","volume":"58","author":"Deng","year":"2009","journal-title":"Diabetes"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"235","DOI":"10.2337\/db17-0356","article-title":"Exosomes from adipose-derived stem cells attenuate adipose inflammation and obesity through polarizing M2 macrophages and beiging in white adipose tissue","volume":"67","author":"Zhao","year":"2018","journal-title":"Diabetes"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1016\/j.biopha.2018.05.019","article-title":"Platelet rich plasma, stromal vascular fraction and autologous conditioned serum in treatment of knee osteoarthritis","volume":"104","author":"Fotouhi","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13018-017-0521-3","article-title":"The temporal effect of platelet-rich plasma on pain and physical function in the treatment of knee osteoarthritis: Systematic review and meta-analysis of randomized controlled trials","volume":"12","author":"Shen","year":"2017","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1097\/MOH.0b013e3283632e6b","article-title":"Advances in platelet granule biology","volume":"20","author":"Koseoglu","year":"2013","journal-title":"Curr. Opin. Hematol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2617","DOI":"10.1182\/bloodadvances.2018028969","article-title":"Mechanism of platelet \u03b1-granule biogenesis: Study of cargo transport and the VPS33B-VPS16B complex in a model system","volume":"3","author":"Ambrosio","year":"2019","journal-title":"Blood Adv."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1007\/s00296-019-04337-1","article-title":"Characterization of cell-derived microparticles in synovial fluid and plasma of patients with rheumatoid arthritis","volume":"39","author":"Michael","year":"2019","journal-title":"Rheumatol. Int."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2019\/6720819","article-title":"Circulating CD3+HLA-DR+extracellular vesicles as a marker for Th1\/Tc1-Type immune responses","volume":"2019","author":"Oba","year":"2019","journal-title":"J. Immunol. Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2892","DOI":"10.1073\/pnas.0409781102","article-title":"The induction of matrix metalloproteinase and cytokine expression in synovial fibroblasts stimulated with immune cell microparticles","volume":"102","author":"Distler","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1136\/annrheumdis-2014-206965","article-title":"Activated human B cells induce inflammatory fibroblasts with cartilage-destructive properties and become functionally suppressed in return","volume":"75","author":"Zimmermann","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.3389\/fimmu.2019.01989","article-title":"Synovial tissue inflammation mediated by autoimmune T cells","volume":"10","author":"Takeuchi","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.intimp.2019.03.008","article-title":"T-cells interact with B cells, dendritic cells, and fibroblast-like synoviocytes as hub-like key cells in rheumatoid arthritis","volume":"70","author":"Hu","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref_98","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_99","first-page":"57","article-title":"Exosomes in intercellular communication and implications for osteoarthritis","volume":"59","author":"Asghar","year":"2019","journal-title":"Rheumatology (Oxford)"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/978-1-4939-9769-5_4","article-title":"Exosomes extraction and identification","volume":"2054","author":"Wu","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1515\/cclm-2018-1297","article-title":"Comparison of six commercial serum exosome isolation methods suitable for clinical laboratories. Effect in cytokine analysis","volume":"57","author":"Rebmann","year":"2019","journal-title":"Clin. Chem. Lab. Med. (CCLM)"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/978-1-4939-2550-6_15","article-title":"A Protocol for exosome isolation and characterization: Evaluation of ultracentrifugation, density-gradient separation, and immunoaffinity capture methods","volume":"1295","author":"Greening","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"3684","DOI":"10.7150\/thno.41580","article-title":"Progress, opportunity, and perspective on exosome isolation\u2014efforts for efficient exosome-based theranostics","volume":"10","author":"Yang","year":"2020","journal-title":"Theranostics"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Helwa, I., Cai, J., Drewry, M.D., Zimmerman, A., Dinkins, M.B., Khaled, M.L., Seremwe, M., Dismuke, W.M., Bieberich, E., and Stamer, W.D. (2017). A comparative study of serum exosome isolation using differential ultracentrifugation and three commercial reagents. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0170628"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"221","DOI":"10.3389\/fimmu.2020.00221","article-title":"Engineered tumor-derived extracellular vesicles: Potentials in cancer immunotherapy","volume":"11","author":"Taghikhani","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"6631","DOI":"10.1039\/C5AN00688K","article-title":"Exosomes: Improved methods to characterize their morphology, RNA content, and surface protein biomarkers","volume":"140","author":"Wu","year":"2015","journal-title":"Analyst"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1194\/jlr.R084343","article-title":"Exosomal lipid composition and the role of ether lipids and phosphoinositides in exosome biology","volume":"60","author":"Skotland","year":"2019","journal-title":"J. Lipid Res."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Gurunathan, S., Kang, M.-H., Jeyaraj, M., Qasim, M., and Kim, J.-H. (2019). Review of the isolation, characterization, biological function, and multifarious therapeutic approaches of exosomes. Cells, 8.","DOI":"10.3390\/cells8040307"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"20360","DOI":"10.3402\/jev.v2i0.20360","article-title":"Standardization of sample collection, isolation and analysis methods in extracellular vesicle research","volume":"2","author":"Witwer","year":"2013","journal-title":"J. Extracell. Vesicles"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/23144599.2019.1704992","article-title":"Preservation techniques of stem cells extracellular vesicles: A gate for manufacturing of clinical grade therapeutic extracellular vesicles and long-term clinical trials","volume":"8","author":"Bahr","year":"2020","journal-title":"Int. J. Veter- Sci. Med."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1248\/bpb.b18-00133","article-title":"Possibility of exosome-based therapeutics and challenges in production of exosomes eligible for therapeutic application","volume":"41","author":"Yamashita","year":"2018","journal-title":"Biol. Pharm. Bull."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijpharm.2018.10.032","article-title":"Preservation of exosomes at room temperature using lyophilization","volume":"553","author":"Charoenviriyakul","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.3389\/fphar.2018.01199","article-title":"To protect and to preserve: Novel preservation strategies for extracellular vesicles","volume":"9","author":"Kusuma","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_114","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_115","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_116","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13287-019-1445-0","article-title":"Mesenchymal stem cell-derived exosomes: A new therapeutic approach to osteoarthritis?","volume":"10","author":"Mianehsaz","year":"2019","journal-title":"Stem Cell Res. Ther."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.bbrc.2020.04.159","article-title":"Mechanical stress promotes angiogenesis through fibroblast exosomes","volume":"533","author":"Xie","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s13287-019-1142-z","article-title":"Low-intensity pulsed ultrasound promotes chondrogenesis of mesenchymal stem cells via regulation of autophagy","volume":"10","author":"Wang","year":"2019","journal-title":"Stem Cell Res. Ther."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.actbio.2020.12.034","article-title":"Hypoxic pretreatment of small extracellular vesicles mediates cartilage repair in osteoarthritis by delivering miR-216a-5p","volume":"122","author":"Rong","year":"2021","journal-title":"Acta Biomater."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1186\/s13287-021-02317-6","article-title":"Curcumin-primed human BMSC-derived extracellular vesicles reverse IL-1\u03b2-induced catabolic responses of OA chondrocytes by upregulating miR-126-3p","volume":"12","author":"Li","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"120539","DOI":"10.1016\/j.biomaterials.2020.120539","article-title":"Exosome-mediated delivery of kartogenin for chondrogenesis of synovial fluid-derived mesenchymal stem cells and cartilage regeneration","volume":"269","author":"Xu","year":"2021","journal-title":"Biomaterials"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/s00441-020-03319-1","article-title":"TGF-\u03b21-modified MSC-derived exosomal miR-135b attenuates cartilage injury via promoting M2 synovial macrophage polarization by targeting MAPK6","volume":"384","author":"Wang","year":"2021","journal-title":"Cell Tissue Res."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1002\/iub.2414","article-title":"ATF4 -modified serum exosomes derived from osteoarthritic mice inhibit osteoarthritis by inducing autophagy","volume":"73","author":"Wang","year":"2021","journal-title":"IUBMB Life"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"67","DOI":"10.31138\/mjr.29.2.67","article-title":"The involvement of microRNAs in osteoarthritis and recent developments: A narrative review","volume":"29","author":"Panagopoulos","year":"2018","journal-title":"Mediterr. J. Rheumatol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-017-01905-y","article-title":"Gender-specific differential expression of exosomal miRNA in synovial fluid of patients with osteoarthritis","volume":"7","author":"Kolhe","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.pharmthera.2017.02.020","article-title":"Exosomes: Therapy delivery tools and biomarkers of diseases","volume":"174","author":"Barile","year":"2017","journal-title":"Pharmacol. Ther."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1039\/D0NR07622H","article-title":"Exosome-mediated delivery of gene vectors for gene therapy","volume":"13","author":"Duan","year":"2020","journal-title":"Nanoscale"},{"key":"ref_128","first-page":"73","article-title":"Extracellular vesicles: Potential role in osteoarthritis regenerative medicine","volume":"21","author":"Wu","year":"2020","journal-title":"J. Orthop. Transl."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"118987","DOI":"10.1016\/j.lfs.2020.118987","article-title":"MiR-129-5p shuttled by human synovial mesenchymal stem cell-derived exosomes relieves IL-1\u03b2 induced osteoarthritis via targeting HMGB1","volume":"269","author":"Qiu","year":"2021","journal-title":"Life Sci."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13287-021-02431-5","article-title":"Exosome-transported circRNA_0001236 enhances chondrogenesis and suppress cartilage degradation via the miR-3677-3p\/Sox9 axis","volume":"12","author":"Mao","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"531","DOI":"10.2147\/IJN.S191313","article-title":"Drug-loaded exosomal preparations from different cell types exhibit distinctive loading capability, yield, and antitumor efficacies: A comparative analysis","volume":"14","author":"Kanchanapally","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1016\/j.nano.2017.03.001","article-title":"Milk-derived exosomes for oral delivery of paclitaxel","volume":"13","author":"Agrawal","year":"2017","journal-title":"Nanomedicine"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11010-019-03545-4","article-title":"Exosomes: Cell-created drug delivery systems","volume":"459","author":"Familtseva","year":"2019","journal-title":"Mol. Cell. Biochem."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1007\/s40259-020-00434-x","article-title":"Designer exosomes: A new platform for biotechnology therapeutics","volume":"34","author":"Jafari","year":"2020","journal-title":"BioDrugs"},{"key":"ref_135","first-page":"61","article-title":"Drug loading techniques for exosome-based drug delivery systems","volume":"76","author":"Xi","year":"2021","journal-title":"Pharmazie"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"5261","DOI":"10.7150\/thno.33183","article-title":"Focused ultrasound-augmented targeting delivery of nanosonosensitizers from homogenous exosomes for enhanced sonodynamic cancer therapy","volume":"9","author":"Liu","year":"2019","journal-title":"Theranostics"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1146\/annurev-biochem-013118-111902","article-title":"Exosomes","volume":"88","author":"Pegtel","year":"2019","journal-title":"Annu. Rev. Biochem."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"9355","DOI":"10.2147\/IJN.S281890","article-title":"Advances in exosome-based drug delivery and tumor targeting: From tissue distribution to intracellular fate","volume":"15","author":"Shao","year":"2020","journal-title":"Int. J. Nanomed."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"e1800161","DOI":"10.1002\/pmic.201800161","article-title":"Proteomic and post-translational modification profiling of exosome-mimetic nanovesicles compared to exosomes","volume":"19","author":"Kenari","year":"2019","journal-title":"Proteom."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"2838","DOI":"10.1016\/j.ymthe.2018.09.015","article-title":"Exosomes produced from 3D cultures of MSCs by tangential flow filtration show higher yield and improved activity","volume":"26","author":"Haraszti","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_141","first-page":"1","article-title":"Exosome-mimetic nanovesicles from hepatocytes promote hepatocyte proliferation in vitro and liver regeneration in vivo","volume":"8","author":"Wu","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.3389\/fphar.2018.01116","article-title":"A new approach for loading anticancer drugs into mesenchymal stem cell-derived exosome mimetics for cancer therapy","volume":"9","author":"Kalimuthu","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"5828","DOI":"10.7150\/thno.34837","article-title":"Homotypic cell membrane-cloaked biomimetic nanocarrier for the targeted chemotherapy of hepatocellular carcinoma","volume":"9","author":"Liu","year":"2019","journal-title":"Theranostics"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"34937","DOI":"10.1038\/srep34937","article-title":"Vectorization of biomacromolecules into cells using extracellular vesicles with enhanced internalization induced by macropinocytosis","volume":"6","author":"Nakase","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1039\/C9BM01232J","article-title":"Nanogel hybrid assembly for exosome intracellular delivery: Effects on endocytosis and fusion by exosome surface polymer engineering","volume":"8","author":"Sawada","year":"2020","journal-title":"Biomater. Sci."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1700611","DOI":"10.1002\/advs.201700611","article-title":"Exosome-liposome hybrid nanoparticles deliver CRISPR\/Cas9 system in MSCs","volume":"5","author":"Lin","year":"2018","journal-title":"Adv. Sci."},{"key":"ref_147","first-page":"29","article-title":"Virus-mimetic fusogenic exosomes for direct delivery of integral membrane proteins to target cell membranes","volume":"29","author":"Yang","year":"2017","journal-title":"Adv. Mater."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.actbio.2019.07.006","article-title":"Cell-free synthesis of connexin 43-integrated exosome-mimetic nanoparticles for siRNA delivery","volume":"96","author":"Lu","year":"2019","journal-title":"Acta Biomater."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"8","DOI":"10.3389\/fbioe.2020.575057","article-title":"Immunomodulation of MSCs and MSC-derived extracellular vesicles in osteoarthritis","volume":"8","author":"Zhao","year":"2020","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"4430","DOI":"10.1039\/C7NR00352H","article-title":"Integration of stem cell-derived exosomes with in situ hydrogel glue as a promising tissue patch for articular cartilage regeneration","volume":"9","author":"Liu","year":"2017","journal-title":"Nanoscale"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"30081","DOI":"10.1021\/acsami.8b08449","article-title":"Enhanced therapeutic effects of mesenchymal stem cell-derived exosomes with an injectable hydrogel for hindlimb ischemia treatment","volume":"10","author":"Zhang","year":"2018","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"8694","DOI":"10.1021\/acsnano.9b00376","article-title":"The kinetics of small extracellular vesicle delivery impacts skin tissue regeneration","volume":"13","author":"Cardoso","year":"2019","journal-title":"ACS Nano"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/s41565-020-0636-2","article-title":"Matrix mechanics and water permeation regulate extracellular vesicle transport","volume":"15","author":"Lenzini","year":"2020","journal-title":"Nat. Nanotechnol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"121169","DOI":"10.1016\/j.biomaterials.2021.121169","article-title":"Injectable Mussel-Inspired highly adhesive hydrogel with exosomes for endogenous cell recruitment and cartilage defect regeneration","volume":"278","author":"Zhang","year":"2021","journal-title":"Biomater."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"e2000082","DOI":"10.1002\/biot.202000082","article-title":"Mesenchymal stem cell-derived exosomes for effective cartilage tissue repair and treatment of osteoarthritis","volume":"15","author":"Kim","year":"2020","journal-title":"Biotechnol. J."},{"key":"ref_156","first-page":"112881","article-title":"Identification of exosomal mRNA, lncRNA and circRNA signatures in an osteoarthritis synovial fluid-exosomal study","volume":"410","author":"Xiaomin","year":"2021","journal-title":"Exp. Cell Res."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1172\/jci.insight.125019","article-title":"Senescence cell\u2013associated extracellular vesicles serve as osteoarthritis disease and therapeutic markers","volume":"4","author":"Jeon","year":"2019","journal-title":"JCI Insight"},{"key":"ref_158","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_159","doi-asserted-by":"crossref","first-page":"eaat8800","DOI":"10.1126\/scitranslmed.aat8800","article-title":"Cartilage-penetrating nanocarriers improve delivery and efficacy of growth factor treatment of osteoarthritis","volume":"10","author":"Geiger","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1002\/jor.22841","article-title":"A rabbit model demonstrates the influence of cartilage thickness on intra-articular drug delivery and retention within cartilage","volume":"33","author":"Bajpayee","year":"2015","journal-title":"J. Orthop. Res."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"6749","DOI":"10.2147\/IJN.S327059","article-title":"Potential of exosomes as cell-free therapy in articular cartilage regeneration: A review","volume":"16","author":"Ng","year":"2021","journal-title":"Int. J. Nanomed."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.biomaterials.2013.09.091","article-title":"Avidin as a model for charge driven transport into cartilage and drug delivery for treating early stage post-traumatic osteoarthritis","volume":"35","author":"Bajpayee","year":"2014","journal-title":"Biomater."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/nrrheum.2016.210","article-title":"Cartilage-targeting drug delivery: Can electrostatic interactions help?","volume":"13","author":"Bajpayee","year":"2017","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"100898","DOI":"10.1016\/j.nantod.2020.100898","article-title":"Overcoming negatively charged tissue barriers: Drug delivery using cationic peptides and proteins","volume":"34","author":"Vedadghavami","year":"2020","journal-title":"Nano Today"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.actbio.2018.12.004","article-title":"Cartilage penetrating cationic peptide carriers for applications in drug delivery to avascular negatively charged tissues","volume":"93","author":"Vedadghavami","year":"2019","journal-title":"Acta Biomater."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.jconrel.2019.12.020","article-title":"Multi-arm Avidin nano-construct for intra-cartilage delivery of small molecule drugs","volume":"318","author":"He","year":"2020","journal-title":"J. Control. Release"},{"key":"ref_167","first-page":"1","article-title":"Safety and efficacy of umbilical cord-derived Wharton\u2019s jelly compared to hyaluronic acid and saline for knee osteoarthritis: Study protocol for a randomized, controlled, single-blind, multi-center trial","volume":"16","author":"Gupta","year":"2021","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_168","first-page":"1","article-title":"Umbilical cord-derived Wharton\u2019s jelly for treatment of knee osteoarthritis: Study protocol for a non-randomized, open-label, multi-center trial","volume":"16","author":"Gupta","year":"2021","journal-title":"J. Orthop. Surg. Res."}],"container-title":["Bioengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-5354\/9\/3\/99\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:28:45Z","timestamp":1760135325000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-5354\/9\/3\/99"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,27]]},"references-count":168,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["bioengineering9030099"],"URL":"https:\/\/doi.org\/10.3390\/bioengineering9030099","relation":{},"ISSN":["2306-5354"],"issn-type":[{"value":"2306-5354","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,27]]}}}