{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T15:02:44Z","timestamp":1785164564028,"version":"3.55.0"},"reference-count":86,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Curr. Issues Mol. Biol.","CIMB"],"abstract":"<jats:p>Osteoarthritis (OA) is a chronic degenerative joint disorder characterized primarily by cartilage degradation and extensive inflammation. Its pathological progression is closely associated with the dysregulation of critical signaling pathways; consequently, the therapeutic targets of these pathways have become crucial for intervening underlying mechanisms of cartilage damage. Extensive laboratory studies have found that mesenchymal stem cell-derived exosomes (MSC-Exos) can deliver bioactive cargoes such as microRNAs (miRNAs) and antioxidant enzymes to modulate these targets, thereby exerting therapeutic effects that include mitigating inflammation, inhibiting chondrocyte apoptosis, maintaining extracellular matrix homeostasis, and promoting tissue repair. However, the clinical translation of MSC-Exos is significantly hampered by inherent limitations, including source variability, low stability, and rapid clearance from the joint cavity. Hydrogels, recognized for their excellent biocompatibility, three-dimensional biomimetic architecture, and controlled drug release capabilities, have been used for OA therapy. Therefore, this review summarizes current research on the combined application of exosomes and hydrogels for OA treatment, and proposes optimization strategies for exosome preconditioning, hydrogel material selection, and hydrogel functional design. These strategies aim to enhance exosome functionality as well as enable sustained responsive, and localized exosome release within the joint, thereby improving the therapeutic efficacy for OA.<\/jats:p>","DOI":"10.3390\/cimb48080764","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T14:08:14Z","timestamp":1785161294000},"page":"764","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mesenchymal Stem Cell Exosomes in Combination with Hydrogels for Osteoarthritis: From Exploratory Applications to Optimization and Translational Outlook"],"prefix":"10.3390","volume":"48","author":[{"given":"Xuemeng","family":"He","sequence":"first","affiliation":[{"name":"National Institutes for Food and Drug Control (NIFDC), No. 31, Huatuo Road, Daxing District, Beijing 102629, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5567-196X","authenticated-orcid":false,"given":"Menghang","family":"Guo","sequence":"additional","affiliation":[{"name":"National Institutes for Food and Drug Control (NIFDC), No. 31, Huatuo Road, Daxing District, Beijing 102629, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8227-9751","authenticated-orcid":false,"given":"Huan","family":"Lian","sequence":"additional","affiliation":[{"name":"National Institutes for Food and Drug Control (NIFDC), No. 31, Huatuo Road, Daxing District, Beijing 102629, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7484-7067","authenticated-orcid":false,"given":"Liang","family":"Chen","sequence":"additional","affiliation":[{"name":"National Institutes for Food and Drug Control (NIFDC), No. 31, Huatuo Road, Daxing District, Beijing 102629, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1186\/s13018-019-1394-4","article-title":"PI3K\/Akt inhibitor partly decreases TNF-\u03b1-induced activation of fibroblast-like synoviocytes in osteoarthritis","volume":"14","author":"Liu","year":"2019","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e2307338","DOI":"10.1002\/advs.202307338","article-title":"Inflammatory Fibroblast-Like Synoviocyte-Derived Exosomes Aggravate Osteoarthritis via Enhancing Macrophage Glycolysis","volume":"11","author":"Liu","year":"2024","journal-title":"Adv. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e202451381","DOI":"10.1002\/eji.202451381","article-title":"Metabolic Reprogramming in Stromal and Immune Cells in Rheumatoid Arthritis and Osteoarthritis: Therapeutic Possibilities","volume":"55","author":"Henry","year":"2025","journal-title":"Eur. J. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/j.cstres.2024.11.001","article-title":"Regulation of chondrocyte apoptosis in osteoarthritis by endoplasmic reticulum stress","volume":"29","author":"Li","year":"2024","journal-title":"Cell Stress Chaperones"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1097\/BOR.0000000000000923","article-title":"Inflammation in osteoarthritis: The latest progress and ongoing challenges","volume":"35","author":"Knights","year":"2023","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"16044","DOI":"10.1038\/boneres.2016.44","article-title":"Osteoarthritis: Toward a comprehensive understanding of pathological mechanism","volume":"5","author":"Chen","year":"2017","journal-title":"Bone Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"106014","DOI":"10.1016\/j.jbspin.2025.106014","article-title":"Platelet-rich plasma and knee osteoarthritis: A critical overview of the multiple biases and methodological complexity","volume":"93","author":"Bard","year":"2026","journal-title":"Jt. Bone Spine"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1007\/s13770-025-00716-x","article-title":"Exosomes Extracted from Human Umbilical Cord MSCs Contribute to Osteoarthritic Cartilage and Chondrocytes Repair Through Enhancing Autophagy While Suppressing the Wnt\/\u03b2-Catenin Pathway","volume":"22","author":"Qin","year":"2025","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"20417314241312563","DOI":"10.1177\/20417314241312563","article-title":"Cell-free osteoarthritis treatment with dual-engineered chondrocyte-targeted extracellular vesicles derived from mechanical loading primed mesenchymal stem cells","volume":"16","author":"Wang","year":"2025","journal-title":"J. Tissue Eng."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Chu, C.H., Lee, R.P., Wu, W.T., Chen, I.H., Yeh, K.T., and Wang, C.C. (2024). Advancing Osteoarthritis Treatment: The Therapeutic Potential of Mesenchymal Stem Cell-Derived Exosomes and Biomaterial Integration. Biomedicines, 12.","DOI":"10.3390\/biomedicines12112478"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Gan, X., Wang, X., Huang, Y., Li, G., and Kang, H. (2024). Applications of Hydrogels in Osteoarthritis Treatment. Biomedicines, 12.","DOI":"10.3390\/biomedicines12040923"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/s41392-023-01330-w","article-title":"Osteoarthritis: Pathogenic signaling pathways and therapeutic targets","volume":"8","author":"Yao","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Choi, M.C., Jo, J., Park, J., Kang, H.K., and Park, Y. (2019). NF-\u03baB Signaling Pathways in Osteoarthritic Cartilage Destruction. Cells, 8.","DOI":"10.3390\/cells8070734"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"103919","DOI":"10.4252\/wjsc.v17.i4.103919","article-title":"Human umbilical cord mesenchymal stem cell-derived exosomal miR-199a-3p inhibits the MAPK4\/NF-\u03baB signaling pathway to relieve osteoarthritis","volume":"17","author":"Chen","year":"2025","journal-title":"World J. Stem Cells"},{"key":"ref_15","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_16","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_17","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1186\/s13287-025-04412-4","article-title":"Unveiling the potential of MSC extracellular vesicles: MiR-122-5p enhancing chondrocyte regeneration in osteoarthritis via autophagy mechanism","volume":"16","author":"Zhang","year":"2025","journal-title":"Stem Cell Res. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"9455152","DOI":"10.1155\/2022\/9455152","article-title":"miR-3960 from Mesenchymal Stem Cell-Derived Extracellular Vesicles Inactivates SDC1\/Wnt\/\u03b2-Catenin Axis to Relieve Chondrocyte Injury in Osteoarthritis by Targeting PHLDA2","volume":"2022","author":"Ye","year":"2022","journal-title":"Stem Cells Int."},{"key":"ref_19","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_20","doi-asserted-by":"crossref","first-page":"115343","DOI":"10.1016\/j.bcp.2022.115343","article-title":"Exosome modification to better alleviates endoplasmic reticulum stress induced chondrocyte apoptosis and osteoarthritis","volume":"206","author":"Wang","year":"2022","journal-title":"Biochem. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Xia, C., Dai, Z., Jin, Y., and Chen, P. (2021). Emerging Antioxidant Paradigm of Mesenchymal Stem Cell-Derived Exosome Therapy. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.727272"},{"key":"ref_22","first-page":"57","article-title":"Exosomes in intercellular communication and implications for osteoarthritis","volume":"59","author":"Asghar","year":"2020","journal-title":"Rheumatology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1007\/s12031-018-1071-9","article-title":"Exosomes Secreted by Adipose-Derived Stem Cells Contribute to Angiogenesis of Brain Microvascular Endothelial Cells Following Oxygen-Glucose Deprivation In Vitro Through MicroRNA-181b\/TRPM7 Axis","volume":"65","author":"Yang","year":"2018","journal-title":"J. Mol. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"D1670","DOI":"10.1093\/nar\/gkae973","article-title":"Generic Diagramming Platform (GDP): A comprehensive database of high-quality biomedical graphics","volume":"53","author":"Jiang","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.21037\/atm-21-684","article-title":"Dexamethasone-loaded thermo-sensitive hydrogel attenuates osteoarthritis by protecting cartilage and providing effective pain relief","volume":"9","author":"Wang","year":"2021","journal-title":"Ann. Transl. Med."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Wei, X., Gao, J., Zhao, Y., Zhao, Y., Guo, L., Chen, C., Duan, Z., Li, P., and Wei, L. (2016). Intra-Articular Injection of Cross-Linked Hyaluronic Acid-Dexamethasone Hydrogel Attenuates Osteoarthritis: An Experimental Study in a Rat Model of Osteoarthritis. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17040411"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"40711","DOI":"10.1021\/acsami.2c12703","article-title":"Nanoarchitectonics of Cartilage-Targeting Hydrogel Microspheres with Reactive Oxygen Species Responsiveness for the Repair of Osteoarthritis","volume":"14","author":"Yu","year":"2022","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_28","first-page":"466","article-title":"Enhanced Chondrogenic Potential and Osteoarthritis Treatment Using Cyaonoside A-Induced MSC Delivered via a Hyaluronic Acid-Based Hydrogel System","volume":"17","author":"An","year":"2025","journal-title":"Aging Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6257","DOI":"10.1038\/s41467-023-41594-y","article-title":"Injectable and biodegradable piezoelectric hydrogel for osteoarthritis treatment","volume":"14","author":"Vinikoor","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2008793","DOI":"10.1002\/adma.202008793","article-title":"Polymeric Aggregate-Embodied Hybrid Nitric-Oxide-Scavenging and Sequential Drug-Releasing Hydrogel for Combinatorial Treatment of Rheumatoid Arthritis","volume":"33","author":"Kim","year":"2021","journal-title":"Adv. Mater."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4560","DOI":"10.1038\/s41598-021-83208-x","article-title":"Repair of full-thickness articular cartilage defects using IEIK13 self-assembling peptide hydrogel in a non-human primate model","volume":"11","author":"Dufour","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e34192","DOI":"10.1016\/j.heliyon.2024.e34192","article-title":"Mechanism study of BMSC-exosomes combined with hyaluronic acid gel in the treatment of posttraumatic osteoarthritis","volume":"10","author":"Liu","year":"2024","journal-title":"Heliyon"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e2402923","DOI":"10.1002\/adhm.202402923","article-title":"Controlled Release of Human Dental Pulp Stem Cell-Derived Exosomes from Hydrogels Attenuates Temporomandibular Joint Osteoarthritis","volume":"14","author":"Tian","year":"2025","journal-title":"Adv. Healthc. Mater."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1186\/s12951-024-02713-z","article-title":"Advancing osteoarthritis therapy with GMOCS hydrogel-loaded BMSCs-exos","volume":"22","author":"Zhou","year":"2024","journal-title":"J. Nanobiotechnology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e03492","DOI":"10.1002\/smll.202503492","article-title":"Self-Assembled Bifunctional Exosomes Simplify Chondrocyte-Targeted Sustained-Release Systems in Decellularized Cartilage Microgels for Synergistic Osteoarthritis Therapy","volume":"21","author":"Deng","year":"2025","journal-title":"Small"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"41729","DOI":"10.1021\/acsami.5c07676","article-title":"Exosome-Functionalized Hydrogels Improve Cartilage Repair by Modulating BMSCs Migration and Differentiation","volume":"17","author":"Pei","year":"2025","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_37","first-page":"73","article-title":"CAP-CD56(+)CD271(+) BMSCs exos-loaded PVA\/SA sustained-release hydrogel attenuates chondrocyte senescence and ameliorates lumbar facet joint osteoarthritis","volume":"57","author":"Xie","year":"2026","journal-title":"Bioact. Mater."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4924","DOI":"10.1021\/acsnano.4c16785","article-title":"Remodeling the Proinflammatory Microenvironment in Osteoarthritis through Interleukin-1 Beta Tailored Exosome Cargo for Inflammatory Regulation and Cartilage Regeneration","volume":"19","author":"Chen","year":"2025","journal-title":"ACS Nano"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e2300315","DOI":"10.1002\/adhm.202300315","article-title":"Treatment with Mesenchymal Stem Cell-Derived Nanovesicle-Containing Gelatin Methacryloyl Hydrogels Alleviates Osteoarthritis by Modulating Chondrogenesis and Macrophage Polarization","volume":"12","author":"Pang","year":"2023","journal-title":"Adv. Healthc. Mater."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"123595","DOI":"10.1016\/j.biomaterials.2025.123595","article-title":"Self-supported DNA hydrogel facilitates microenvironment remodeling and cartilage repair to prevent osteoarthritis progression via an ambidextrous strategy","volume":"325","author":"Liu","year":"2026","journal-title":"Biomaterials"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1186\/s12951-023-01865-8","article-title":"Exosome inspired photo-triggered gelation hydrogel composite on modulating immune pathogenesis for treating rheumatoid arthritis","volume":"21","author":"Rui","year":"2023","journal-title":"J. Nanobiotechnology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.jmst.2022.09.061","article-title":"Wharton\u2019s jelly MSC-derived extracellular vehicles\u2014Loaded hyaluronic acid-alginate adhesives for treatment of osteoarthritis","volume":"142","author":"Zhao","year":"2023","journal-title":"J. Mater. Sci. Technol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"115715","DOI":"10.1016\/j.biopha.2023.115715","article-title":"Exosomes loaded with chondrogenic stimuli agents combined with 3D bioprinting hydrogel in the treatment of osteoarthritis and cartilage degeneration","volume":"168","author":"Zhang","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"13358","DOI":"10.1021\/acsnano.3c01612","article-title":"Cell-Free Osteoarthritis Treatment with Sustained-Release of Chondrocyte-Targeting Exosomes from Umbilical Cord-Derived Mesenchymal Stem Cells to Rejuvenate Aging Chondrocytes","volume":"17","author":"Cao","year":"2023","journal-title":"ACS Nano"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1186\/s12951-023-02050-7","article-title":"Injectable photocrosslinking spherical hydrogel-encapsulated targeting peptide-modified engineered exosomes for osteoarthritis therapy","volume":"21","author":"Wan","year":"2023","journal-title":"J. Nanobiotechnology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"123088","DOI":"10.1016\/j.biomaterials.2025.123088","article-title":"Hydrogel-integrated exosome mimetics derived from osteogenically induced mesenchymal stem cells in spheroid culture enhance bone regeneration","volume":"317","author":"Xu","year":"2025","journal-title":"Biomaterials"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"20417314241306681","DOI":"10.1177\/20417314241306681","article-title":"Harnessing bone marrow mesenchymal stem cell-derived extracellular vesicles and biomimetic peptide WKYMVm in self-healing hydrogel for enhanced bone repair in femoral defects","volume":"15","author":"Luo","year":"2024","journal-title":"J. Tissue Eng."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1186\/s12951-023-01871-w","article-title":"Hydrogel armed with Bmp2 mRNA-enriched exosomes enhances bone regeneration","volume":"21","author":"Yang","year":"2023","journal-title":"J. Nanobiotechnology"},{"key":"ref_49","first-page":"100799","article-title":"Bone mesenchymal stem cell-derived exosomes involved co-delivery and synergism effect with icariin via mussel-inspired multifunctional hydrogel for cartilage protection","volume":"18","author":"Zeng","year":"2023","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"42658","DOI":"10.1021\/acsami.5c06750","article-title":"Engineered EVs from 3D-Cultured MSCs for Synergistic Modulation of Inflammatory Microenvironment and Cartilage Regeneration in Osteoarthritis","volume":"17","author":"Fu","year":"2025","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1186\/s12951-024-02765-1","article-title":"Stem cell recruitment polypeptide hydrogel microcarriers with exosome delivery for osteoarthritis treatment","volume":"22","author":"Yang","year":"2024","journal-title":"J. Nanobiotechnology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s12951-022-01245-8","article-title":"Exosomes derived from platelet-rich plasma administration in site mediate cartilage protection in subtalar osteoarthritis","volume":"20","author":"Zhang","year":"2022","journal-title":"J. Nanobiotechnology"},{"key":"ref_53","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_54","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1186\/s12951-024-02795-9","article-title":"Engineering exosomes derived from TNF-\u03b1 preconditioned IPFP-MSCs enhance both yield and therapeutic efficacy for osteoarthritis","volume":"22","author":"Wu","year":"2024","journal-title":"J. Nanobiotechnology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1186\/s13287-025-04416-0","article-title":"Let-7a-5p derived from parathyroid hormone (1-34)-preconditioned BMSCs exosomes delays the progression of osteoarthritis by promoting chondrocyte proliferation and migration","volume":"16","author":"Shao","year":"2025","journal-title":"Stem Cell Res. Ther."},{"key":"ref_56","first-page":"98","article-title":"Secretive derived from hypoxia preconditioned mesenchymal stem cells promote cartilage regeneration and mitigate joint inflammation via extracellular vesicles","volume":"27","author":"Yang","year":"2023","journal-title":"Bioact. Mater."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e3510","DOI":"10.1002\/jgm.3510","article-title":"Exosomes derived from bone marrow mesenchymal stem cells pretreated with decellularized extracellular matrix enhance the alleviation of osteoarthritis through miR-3473b\/phosphatase and tensin homolog axis","volume":"25","author":"Zhang","year":"2023","journal-title":"J. Gene Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1016\/j.jconrel.2025.02.030","article-title":"3D mesenchymal stem cell exosome-functionalized hydrogels for corneal wound healing","volume":"380","author":"Xu","year":"2025","journal-title":"J. Control. Release"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e2200079","DOI":"10.1002\/advs.202200079","article-title":"Transporting Hydrogel via Chinese Acupuncture Needles for Lesion Positioning Therapy","volume":"9","author":"Lin","year":"2022","journal-title":"Adv. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2489","DOI":"10.2174\/0113816128268132231016061548","article-title":"Fabrication and In vitro Evaluation of Carbopol\/Polyvinyl Alcohol-based pH-sensitive Hydrogels for Controlled Drug Delivery","volume":"29","author":"Suhail","year":"2023","journal-title":"Curr. Pharm. Des."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Xiao, Y., Hu, X., Jiang, P., and Qi, Z. (2023). Thermos-responsive hydrogel system encapsulated engineered exosomes attenuate inflammation and oxidative damage in acute spinal cord injury. Front. Bioeng. Biotechnol., 11.","DOI":"10.3389\/fbioe.2023.1216878"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1021\/acs.biomac.1c01636","article-title":"Controlled Release of Exosomes Using Atom Transfer Radical Polymerization-Based Hydrogels","volume":"23","author":"Yerneni","year":"2022","journal-title":"Biomacromolecules"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e2407820","DOI":"10.1002\/advs.202407820","article-title":"Wireless, Programmable, and Refillable Hydrogel Bioelectronics for Enhanced Diabetic Wound Healing","volume":"11","author":"Du","year":"2024","journal-title":"Adv. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"6682","DOI":"10.1016\/j.biomaterials.2012.06.005","article-title":"Cartilage-like mechanical properties of poly (ethylene glycol)-diacrylate hydrogels","volume":"33","author":"Nguyen","year":"2012","journal-title":"Biomaterials"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2309","DOI":"10.1038\/s41467-025-57653-5","article-title":"Cartilage-bioinspired tenacious concrete-like hydrogel verified via in-situ testing","volume":"16","author":"Liu","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1302\/2046-3758.1212.BJR-2023-0021.R2","article-title":"Classification of distinct osteoarthritis subtypes with different knee joint tissues by gene expression profiles","volume":"12","author":"Xue","year":"2023","journal-title":"Bone Jt. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/s13075-025-03561-4","article-title":"Beyond symptomatic alignment: Evaluating the integration of causal mechanisms in matching animal models with human pathotypes in osteoarthritis research","volume":"27","author":"Reihs","year":"2025","journal-title":"Arthritis Res. Ther."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Liu, X., Wei, Q., Lu, L., Cui, S., Ma, K., Zhang, W., Ma, F., Li, H., Fu, X., and Zhang, C. (2023). Immunomodulatory potential of mesenchymal stem cell-derived extracellular vesicles: Targeting immune cells. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1094685"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1038\/s41423-020-00587-3","article-title":"Olfactory ecto-mesenchymal stem cell-derived exosomes ameliorate murine Sj\u00f6gren\u2019s syndrome by modulating the function of myeloid-derived suppressor cells","volume":"18","author":"Rui","year":"2021","journal-title":"Cell Mol. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Reis, M., Mavin, E., Nicholson, L., Green, K., Dickinson, A.M., and Wang, X.N. (2018). Mesenchymal Stromal Cell-Derived Extracellular Vesicles Attenuate Dendritic Cell Maturation and Function. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02538"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"369","DOI":"10.3727\/096368911X582769b","article-title":"The immunosuppressive effect of mesenchymal stromal cells on B lymphocytes is mediated by membrane vesicles","volume":"22","author":"Budoni","year":"2013","journal-title":"Cell Transpl."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Adamo, A., Brandi, J., Caligola, S., Delfino, P., Bazzoni, R., Carusone, R., Cecconi, D., Giugno, R., Manfredi, M., and Robotti, E. (2019). Extracellular Vesicles Mediate Mesenchymal Stromal Cell-Dependent Regulation of B Cell PI3K-AKT Signaling Pathway and Actin Cytoskeleton. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00446"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Blazquez, R., Sanchez-Margallo, F.M., de la Rosa, O., Dalemans, W., Alvarez, V., Tarazona, R., and Casado, J.G. (2014). Immunomodulatory Potential of Human Adipose Mesenchymal Stem Cells Derived Exosomes on in vitro Stimulated T Cells. Front. Immunol., 5.","DOI":"10.3389\/fimmu.2014.00556"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Li, R., Qi, Q., Jiang, X., Gao, Z., Xie, X., Zhao, Y., Cheng, X., Wang, C., Hou, G., and Li, C. (2025). Exosome microsphere\/nano silver loaded injectable antibacterial hydrogel augments anti-infection and healing for scald wound. Front. Microbiol., 16.","DOI":"10.3389\/fmicb.2025.1550276"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Tanga, S., Aucamp, M., and Ramburrun, P. (2023). Injectable Thermoresponsive Hydrogels for Cancer Therapy: Challenges and Prospects. Gels, 9.","DOI":"10.3390\/gels9050418"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"19174","DOI":"10.1039\/D4NR02792B","article-title":"Harnessing exosomes for advanced osteoarthritis therapy","volume":"16","author":"Selvadoss","year":"2024","journal-title":"Nanoscale"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1186\/s12967-025-06623-y","article-title":"Injection of human umbilical cord mesenchymal stem cells exosomes for the treatment of knee osteoarthritis: From preclinical to clinical research","volume":"23","author":"Wang","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1007\/s11095-024-03757-4","article-title":"Quality and Safety Considerations for Therapeutic Products Based on Extracellular Vesicles","volume":"41","author":"Takakura","year":"2024","journal-title":"Pharm. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e12128","DOI":"10.1002\/jev2.12128","article-title":"Molecular evaluation of five different isolation methods for extracellular vesicles reveals different clinical applicability and subcellular origin","volume":"10","author":"Veerman","year":"2021","journal-title":"J. Extracell. Vesicles"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"23978","DOI":"10.1038\/srep23978","article-title":"ExtraPEG: A Polyethylene Glycol-Based Method for Enrichment of Extracellular Vesicles","volume":"6","author":"Rider","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"153034","DOI":"10.1016\/j.tox.2021.153034","article-title":"Iodixanol activation of mast cells: Implications in the pathogenesis of iodixanol-induced delayed cutaneous adverse reactions","volume":"465","author":"Zou","year":"2022","journal-title":"Toxicology"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"3283","DOI":"10.1038\/s41467-024-46327-3","article-title":"Impact of PEG sensitization on the efficacy of PEG hydrogel-mediated tissue engineering","volume":"15","author":"Isaac","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2403199","DOI":"10.1002\/adma.202403199","article-title":"Immunogenicity of Extracellular Vesicles","volume":"36","author":"Xia","year":"2024","journal-title":"Adv. Mater."},{"key":"ref_84","first-page":"103393","article-title":"Scaling up human mesenchymal stem cell manufacturing using bioreactors for clinical uses","volume":"71","author":"Jankovic","year":"2023","journal-title":"Curr. Res. Transl. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1186\/s13287-024-04005-7","article-title":"Different storage and freezing protocols for extracellular vesicles: A systematic review","volume":"15","author":"Ahmadian","year":"2024","journal-title":"Stem Cell Res. Ther."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"5044","DOI":"10.7150\/thno.131621","article-title":"From bench to bedside: The promise and roadblocks of extracellular vesicle therapeutics","volume":"16","author":"Zhang","year":"2026","journal-title":"Theranostics"}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/8\/764\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T14:40:53Z","timestamp":1785163253000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/8\/764"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,27]]},"references-count":86,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["cimb48080764"],"URL":"https:\/\/doi.org\/10.3390\/cimb48080764","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,27]]}}}