{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T02:34:21Z","timestamp":1790217261362,"version":"4.1.0"},"reference-count":142,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF)","doi-asserted-by":"publisher","award":["NRF-2022R1I1A1A01068652"],"award-info":[{"award-number":["NRF-2022R1I1A1A01068652"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["CIMB"],"abstract":"<jats:p>Extracellular vesicles (EVs) are nanoscale, membrane-bound particles secreted by diverse cell types and act as pivotal mediators of intercellular communication during bone regeneration. These vesicles transport bioactive cargo including proteins, lipids, mRNAs, and microRNAs that modulate osteogenesis, angiogenesis, and immune responses within the bone microenvironment. EVs originating from mesenchymal stem cells, osteoblasts, endothelial cells, and macrophages have demonstrated substantial potential to promote bone formation, inhibit bone resorption, and enhance vascularization. This review examines the biogenesis, classification, and cellular uptake mechanisms of EVs, focusing on their roles in osteogenesis and their therapeutic applications in fracture healing, osteoporosis, and bone tissue engineering. Despite their promise, significant challenges remain, including the need for standardization, scalable production, and assessment of long-term safety to enable clinical translation of EV-based therapies. Here, we provide a comprehensive overview of EV biology, elucidate the molecular mechanisms of EVs in bone regeneration, and discuss innovative strategies to optimize their therapeutic efficacy, highlighting their potential as next-generation orthobiologics.<\/jats:p>","DOI":"10.3390\/cimb47080675","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T15:19:02Z","timestamp":1755789542000},"page":"675","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Extracellular Vesicles in Osteogenesis: A Comprehensive Review of Mechanisms and Therapeutic Potential for Bone Regeneration"],"prefix":"10.3390","volume":"47","author":[{"given":"Sreyee","family":"Biswas","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Heritage Institute of Technology, Kolkata 700107, West Bengal, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0658-4604","authenticated-orcid":false,"given":"Prakash","family":"Gangadaran","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea"},{"name":"Cardiovascular Research Institute, Kyungpook National University, Daegu 41944, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandrajeet","family":"Dhara","sequence":"additional","affiliation":[{"name":"School of Biosciences, Apeejay Stya University, Sohna-Palwal Road, Sohna, Gurugram 122103, Haryana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shreya","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Department of Microbiology, St. Xavier\u2019s College, Kolkata 700016, West Bengal, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soumya Deep","family":"Phadikar","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Biology, Indian Institute of Technology (ISM), Dhanbad 826004, Jharkhand, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akash","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Indian Institute of Technology Madras, Chennai 600036, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8099-8127","authenticated-orcid":false,"given":"Atharva Anand","family":"Mahajan","sequence":"additional","affiliation":[{"name":"Advanced Centre for Treatment, Research and Education in Cancer, Navi Mumbai 410210, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranit","family":"Mondal","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, West Bengal, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6016-4487","authenticated-orcid":false,"given":"Debdeep","family":"Chattopadhyay","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, St. Xavier\u2019s College, Kolkata 700016, West Bengal, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trisha","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Department of Microbiology, St. Xavier\u2019s College, Kolkata 700016, West Bengal, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8098-7372","authenticated-orcid":false,"given":"Anuvab","family":"Dey","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, North Guwahati 781039, Assam, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1528-423X","authenticated-orcid":false,"given":"Subhrojyoti","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Indian Institute of Technology Madras, Chennai 600036, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8886-8482","authenticated-orcid":false,"given":"Anand","family":"Krishnan","sequence":"additional","affiliation":[{"name":"Precision Medicine and Integrated Nano-Diagnostics (P-MIND) Research Group, Office of the Dean, Faculty of Health Sciences, University of the Free State, Bloemfontein 9300, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7700-3929","authenticated-orcid":false,"given":"Byeong-Cheol","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea"},{"name":"Cardiovascular Research Institute, Kyungpook National University, Daegu 41944, Republic of Korea"},{"name":"BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea"},{"name":"Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu 41944, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6987-0854","authenticated-orcid":false,"given":"Ramya Lakshmi","family":"Rajendran","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea"},{"name":"Cardiovascular Research Institute, Kyungpook National University, Daegu 41944, Republic of Korea"},{"name":"BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,21]]},"reference":[{"key":"ref_1","first-page":"425","article-title":"Small Extracellular Vesicles with Nanomorphology Memory Promote Osteogenesis","volume":"17","author":"Ma","year":"2022","journal-title":"Bioact. Mater."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Ravi Mythili, V.M., Rajendran, R.L., Arun, R., Thasma Loganathbabu, V.K., Reyaz, D., Nagarajan, A.K., Ahn, B.-C., and Gangadaran, P. (2025). Emerging Strategies for Revascularization: Use of Cell-Derived Extracellular Vesicles and Artificial Nanovesicles in Critical Limb Ischemia. Bioengineering, 12.","DOI":"10.3390\/bioengineering12010092"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Dimitriou, R., Jones, E., McGonagle, D., and Giannoudis, P.V. (2011). Bone Regeneration: Current Concepts and Future Directions. BMC Med., 9.","DOI":"10.1186\/1741-7015-9-66"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Wang, Z.-X., Lin, X., Cao, J., Liu, Y.-W., Luo, Z.-W., Rao, S.-S., Wang, Q., Wang, Y.-Y., Chen, C.-Y., and Zhu, G.-Q. (2024). Young Osteocyte-Derived Extracellular Vesicles Facilitate Osteogenesis by Transferring Tropomyosin-1. J. Nanobiotechnol., 22.","DOI":"10.1186\/s12951-024-02367-x"},{"key":"ref_5","first-page":"100945","article-title":"Extracellular Vesicle-Functionalized Bioactive Scaffolds for Bone Regeneration","volume":"19","author":"Yu","year":"2024","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.cell.2019.02.029","article-title":"Reassessment of Exosome Composition","volume":"177","author":"Jeppesen","year":"2019","journal-title":"Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2981","DOI":"10.1021\/acschemneuro.3c00386","article-title":"Clinical Theragnostic Signature of Extracellular Vesicles in Traumatic Brain Injury (TBI)","volume":"14","author":"Dey","year":"2023","journal-title":"ACS Chem. Neurosci."},{"key":"ref_8","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_9","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_10","doi-asserted-by":"crossref","unstructured":"Eguchi, T., Sogawa, C., Ono, K., Matsumoto, M., Tran, M.T., Okusha, Y., Lang, B.J., Okamoto, K., and Calderwood, S.K. (2020). Cell Stress Induced Stressome Release Including Damaged Membrane Vesicles and Extracellular HSP90 by Prostate Cancer Cells. Cells, 9.","DOI":"10.3390\/cells9030755"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Okusha, Y., Eguchi, T., Tran, M.T., Sogawa, C., Yoshida, K., Itagaki, M., Taha, E.A., Ono, K., Aoyama, E., and Okamura, H. (2020). Extracellular Vesicles Enriched with Moonlighting Metalloproteinase Are Highly Transmissive, Pro-Tumorigenic, and Trans-Activates Cellular Communication Network Factor (CCN2\/CTGF): CRISPR against Cancer. Cancers, 12.","DOI":"10.3390\/cancers12040881"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2306","DOI":"10.1158\/0008-5472.CAN-16-2942","article-title":"MYC Mediates Large Oncosome-Induced Fibroblast Reprogramming in Prostate Cancer","volume":"77","author":"Minciacchi","year":"2017","journal-title":"Cancer Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1038\/s41556-019-0367-5","article-title":"Migrasome Formation Is Mediated by Assembly of Micron-Scale Tetraspanin Macrodomains","volume":"21","author":"Huang","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1016\/j.celrep.2019.01.009","article-title":"Transfer of Functional Cargo in Exomeres","volume":"27","author":"Zhang","year":"2019","journal-title":"Cell Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5876","DOI":"10.1046\/j.0014-2956.2001.02536.x","article-title":"Biosynthesis of the Cancer-Related Sialyl-Alpha 2,6-Lactosaminyl Epitope in Colon Cancer Cell Lines Expressing Beta-Galactoside Alpha 2,6-Sialyltransferase under a Constitutive Promoter","volume":"268","author":"Chiricolo","year":"2001","journal-title":"Eur. J. Biochem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1535750","DOI":"10.1080\/20013078.2018.1535750","article-title":"Minimal Information for Studies of Extracellular Vesicles 2018 (MISEV2018): A Position Statement of the International Society for Extracellular Vesicles and Update of the MISEV2014 Guidelines","volume":"7","author":"Witwer","year":"2018","journal-title":"J. Extracell. Vesicles"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Gangadaran, P., Khan, F., Rajendran, R.L., Onkar, A., Goenka, A., and Ahn, B.-C. (2024). Unveiling Invisible Extracellular Vesicles: Cutting-Edge Technologies for Their in Vivo Visualization. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol., 16.","DOI":"10.1002\/wnan.2009"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6709","DOI":"10.1021\/acsami.3c16839","article-title":"Smart Nanoscale Extracellular Vesicles in the Brain: Unveiling Their Biology, Diagnostic Potential, and Therapeutic Applications","volume":"16","author":"Onkar","year":"2024","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/j.reth.2024.10.005","article-title":"Extracellular Vesicle Mimetics Engineered from Mesenchymal Stem Cells and Curcumin Promote Fibrosis Regression in a Mouse Model of Thioacetamide-Induced Liver Fibrosis","volume":"26","author":"Gopal","year":"2024","journal-title":"Regen. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"119","DOI":"10.6065\/apem.2016.21.3.119","article-title":"Exosomes as the Source of Biomarkers of Metabolic Diseases","volume":"21","author":"Lee","year":"2016","journal-title":"Ann. Pediatr. Endocrinol. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1146\/annurev-cellbio-101512-122326","article-title":"Biogenesis, Secretion, and Intercellular Interactions of Exosomes and Other Extracellular Vesicles","volume":"30","author":"Colombo","year":"2014","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"22614","DOI":"10.3402\/jev.v2i0.22614","article-title":"Therapeutic MSC Exosomes Are Derived from Lipid Raft Microdomains in the Plasma Membrane","volume":"2","author":"Tan","year":"2013","journal-title":"J. Extracell. Vesicles"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11060-013-1084-8","article-title":"Biogenesis of Extracellular Vesicles (EV): Exosomes, Microvesicles, Retrovirus-like Vesicles, and Apoptotic Bodies","volume":"113","author":"Akers","year":"2013","journal-title":"J. Neurooncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4019","DOI":"10.1002\/pmic.200400876","article-title":"Proteomic Analysis of Melanoma-Derived Exosomes by Two-Dimensional Polyacrylamide Gel Electrophoresis and Mass Spectrometry","volume":"4","author":"Mears","year":"2004","journal-title":"Proteomics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.semcdb.2017.08.020","article-title":"ESCRT-Dependent Cargo Sorting at Multivesicular Endosomes","volume":"74","author":"Frankel","year":"2018","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2678","DOI":"10.1080\/21645515.2017.1363935","article-title":"Extracellular Vesicles as an Efficient Nanoplatform for the Delivery of Therapeutics","volume":"13","author":"Liu","year":"2017","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Campanella, C., Bucchieri, F., Merendino, A.M., Fucarino, A., Burgio, G., Corona, D.F.V., Barbieri, G., David, S., Farina, F., and Zummo, G. (2012). The Odyssey of Hsp60 from Tumor Cells to Other Destinations Includes Plasma Membrane-Associated Stages and Golgi and Exosomal Protein-Trafficking Modalities. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0042008"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/1475-2840-13-37","article-title":"Extracellular Vesicle Markers in Relation to Obesity and Metabolic Complications in Patients with Manifest Cardiovascular Disease","volume":"13","author":"Kranendonk","year":"2014","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1111\/j.1600-0854.2009.00920.x","article-title":"Multivesicular Endosome Biogenesis in the Absence of ESCRTs","volume":"10","author":"Stuffers","year":"2009","journal-title":"Traffic"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2505","DOI":"10.1242\/jcs.115.12.2505","article-title":"The Exosome Pathway in K562 Cells Is Regulated by Rab11","volume":"115","author":"Savina","year":"2002","journal-title":"J. Cell Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.ymeth.2012.01.002","article-title":"Comparison of Ultracentrifugation, Density Gradient Separation, and Immunoaffinity Capture Methods for Isolating Human Colon Cancer Cell Line LIM1863-Derived Exosomes","volume":"56","author":"Tauro","year":"2012","journal-title":"Methods"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1126\/science.1153124","article-title":"Ceramide Triggers Budding of Exosome Vesicles into Multivesicular Endosomes","volume":"319","author":"Trajkovic","year":"2008","journal-title":"Science"},{"key":"ref_33","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_34","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1074\/mcp.M112.021303","article-title":"Two Distinct Populations of Exosomes Are Released from LIM1863 Colon Carcinoma Cell-Derived Organoids","volume":"12","author":"Tauro","year":"2013","journal-title":"Mol. Cell. Proteom. MCP"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1074\/mcp.M111.012732","article-title":"Characterization of Membrane-Shed Microvesicles from Cytokine-Stimulated \u03b2-Cells Using Proteomics Strategies","volume":"11","author":"Palmisano","year":"2012","journal-title":"Mol. Cell. Proteom. MCP"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/j.bbrc.2013.12.070","article-title":"In-Depth Proteomic Analyses of Ovarian Cancer Cell Line Exosomes Reveals Differential Enrichment of Functional Categories Compared to the NCI 60 Proteome","volume":"445","author":"Sinha","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1038\/icb.2010.64","article-title":"MHC Class II-Associated Proteins in B-Cell Exosomes and Potential Functional Implications for Exosome Biogenesis","volume":"88","author":"Buschow","year":"2010","journal-title":"Immunol. Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/ncb1596","article-title":"Exosome-Mediated Transfer of mRNAs and microRNAs Is a Novel Mechanism of Genetic Exchange between Cells","volume":"9","author":"Valadi","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1182\/blood-2011-02-338004","article-title":"Mechanism of Transfer of Functional microRNAs between Mouse Dendritic Cells via Exosomes","volume":"119","author":"Montecalvo","year":"2012","journal-title":"Blood"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"107078","DOI":"10.4252\/wjsc.v17.i5.107078","article-title":"Potential of Mesenchymal Stem Cell-Derived Exosomes in the Treatment of Androgenetic Alopecia","volume":"17","author":"Rajendran","year":"2025","journal-title":"World J. Stem Cells"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"24641","DOI":"10.3402\/jev.v3.24641","article-title":"Routes and Mechanisms of Extracellular Vesicle Uptake","volume":"3","author":"Mulcahy","year":"2014","journal-title":"J. Extracell. Vesicles"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1074\/jbc.M115.686295","article-title":"Fibronectin on the Surface of Myeloma Cell-Derived Exosomes Mediates Exosome-Cell Interactions","volume":"291","author":"Purushothaman","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1016\/j.jacc.2015.02.026","article-title":"Plasma Exosomes Protect the Myocardium from Ischemia-Reperfusion Injury","volume":"65","author":"Vicencio","year":"2015","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1002\/stem.2618","article-title":"Hypoxia Inducible Factor-1\u03b1 Potentiates Jagged 1-Mediated Angiogenesis by Mesenchymal Stem Cell-Derived Exosomes","volume":"35","author":"Ciria","year":"2017","journal-title":"Stem Cells"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Prada, I., and Meldolesi, J. (2016). Binding and Fusion of Extracellular Vesicles to the Plasma Membrane of Their Cell Targets. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17081296"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Whitlock, J.M., and Chernomordik, L.V. (2021). Flagging Fusion: Phosphatidylserine Signaling in Cell-Cell Fusion. J. Biol. Chem., 296.","DOI":"10.1016\/j.jbc.2021.100411"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"34211","DOI":"10.1074\/jbc.M109.041152","article-title":"Microenvironmental pH Is a Key Factor for Exosome Traffic in Tumor Cells","volume":"284","author":"Parolini","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Han, K.-Y., Tran, J.A., Chang, J.-H., Azar, D.T., and Zieske, J.D. (2017). Potential Role of Corneal Epithelial Cell-Derived Exosomes in Corneal Wound Healing and Neovascularization. Sci. Rep., 7.","DOI":"10.1038\/srep40548"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"6581","DOI":"10.7150\/thno.45528","article-title":"Proinflammatory Macrophage-Derived Microvesicles Exhibit Tumor Tropism Dependent on CCL2\/CCR2 Signaling Axis and Promote Drug Delivery via SNARE-Mediated Membrane Fusion","volume":"10","author":"Guo","year":"2020","journal-title":"Theranostics"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Ganesh, B.H., Padinjarathil, H., Rajendran, R.L., Ramani, P., Gangadaran, P., and Ahn, B.-C. (2025). The Role of Extracellular Vesicles in Aging and Age-Related Disorders. Antioxidants, 14.","DOI":"10.3390\/antiox14020177"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Jin, P., Liu, H., Chen, X., Liu, W., and Jiang, T. (2024). From Bench to Bedside: The Role of Extracellular Vesicles in Cartilage Injury Treatment. Biomater. Res., 28.","DOI":"10.34133\/bmr.0110"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Zhuang, Y., Jiang, S., Yuan, C., and Lin, K. (2022). The Potential Therapeutic Role of Extracellular Vesicles in Osteoarthritis. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.1022368"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.semcancer.2021.03.032","article-title":"Exosomes and Extracellular Vesicles: Rethinking the Essential Values in Cancer Biology","volume":"74","author":"Yokoi","year":"2021","journal-title":"Semin. Cancer Biol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Wang, L., Xu, H., Weng, L., Sun, J., Jin, Y., and Xiao, C. (2022). Activation of Cancer Immunotherapy by Nanomedicine. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1041073"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"101093","DOI":"10.1016\/j.bonr.2021.101093","article-title":"Mesenchymal Stromal Cell-Derived Extracellular Vesicles for Bone Regeneration Therapy","volume":"14","author":"Murali","year":"2021","journal-title":"Bone Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e18143","DOI":"10.1111\/jcmm.18143","article-title":"Nerve Growth Factor Promote Osteogenic Differentiation of Dental Pulp Stem Cells through MEK\/ERK Signalling Pathways","volume":"28","author":"Cheng","year":"2024","journal-title":"J. Cell. Mol. Med."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Ansari, S., de Wildt, B.W.M., Vis, M.A.M., de Korte, C.E., Ito, K., Hofmann, S., and Yuana, Y. (2021). Matrix Vesicles: Role in Bone Mineralization and Potential Use as Therapeutics. Pharmaceuticals, 14.","DOI":"10.3390\/ph14040289"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Yuan, F.-L., Wu, Q.-Y., Miao, Z.-N., Xu, M.-H., Xu, R.-S., Jiang, D.-L., Ye, J.-X., Chen, F.-H., Zhao, M.-D., and Wang, H.-J. (2018). Osteoclast-Derived Extracellular Vesicles: Novel Regulators of Osteoclastogenesis and Osteoclast-Osteoblasts Communication in Bone Remodeling. Front. Physiol., 9.","DOI":"10.3389\/fphys.2018.00628"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Ateeq, M., Broadwin, M., Sellke, F.W., and Abid, M.R. (2024). Extracellular Vesicles\u2019 Role in Angiogenesis and Altering Angiogenic Signaling. Med. Sci., 12.","DOI":"10.3390\/medsci12010004"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Liu, G.-S., Chen, H.-A., Chang, C.-Y., Chen, Y.-J., Wu, Y.-Y., Widhibrata, A., Yang, Y.-H., Hsieh, E.-H., Delila, L., and Lin, I.-C. (2025). Platelet-Derived Extracellular Vesicle Drug Delivery System Loaded with Kaempferol for Treating Corneal Neovascularization. Biomaterials, 319.","DOI":"10.1016\/j.biomaterials.2025.123205"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Qin, Y., Wang, L., Gao, Z., Chen, G., and Zhang, C. (2016). Bone Marrow Stromal\/Stem Cell-Derived Extracellular Vesicles Regulate Osteoblast Activity and Differentiation in Vitro and Promote Bone Regeneration in Vivo. Sci. Rep., 6.","DOI":"10.1038\/srep21961"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1186\/s13287-016-0391-3","article-title":"Exosomes\/Tricalcium Phosphate Combination Scaffolds Can Enhance Bone Regeneration by Activating the PI3K\/Akt Signaling Pathway","volume":"7","author":"Zhang","year":"2016","journal-title":"Stem Cell Res. Ther."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1038\/s41401-020-0372-z","article-title":"Advanced Biomaterials for Cancer Immunotherapy","volume":"41","author":"Yang","year":"2020","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Zou, M.-L., Chen, Z.-H., Teng, Y.-Y., Liu, S.-Y., Jia, Y., Zhang, K.-W., Sun, Z.-L., Wu, J.-J., Yuan, Z.-D., and Feng, Y. (2021). The Smad Dependent TGF-\u03b2 and BMP Signaling Pathway in Bone Remodeling and Therapies. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.593310"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2041731420975569","DOI":"10.1177\/2041731420975569","article-title":"Extracellular Vesicles Derived from Human Dental Pulp Stem Cells Promote Osteogenesis of Adipose-Derived Stem Cells via the MAPK Pathway","volume":"11","author":"Jin","year":"2020","journal-title":"J. Tissue Eng."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Vermeulen, S., Tahmasebi Birgani, Z., and Habibovic, P. (2022). Biomaterial-Induced Pathway Modulation for Bone Regeneration. Biomaterials, 283.","DOI":"10.1016\/j.biomaterials.2022.121431"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"6184","DOI":"10.1021\/acsomega.3c08280","article-title":"Extracellular Vesicles and Hydrogels: An Innovative Approach to Tissue Regeneration","volume":"9","author":"Hashemi","year":"2024","journal-title":"ACS Omega"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Wang, M., Zhang, Z., Pan, D., Xin, Z., Bu, F., Zhang, Y., Tian, Q., and Feng, X. (2021). Circulating lncRNA UCA1 and lncRNA PGM5-AS1 Act as Potential Diagnostic Biomarkers for Early-Stage Colorectal Cancer. Biosci. Rep., 41.","DOI":"10.1042\/BSR20211115"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Morhayim, J., van de Peppel, J., Braakman, E., Rombouts, E.W.J.C., Ter Borg, M.N.D., Dudakovic, A., Chiba, H., van der Eerden, B.C.J., Raaijmakers, M.H., and van Wijnen, A.J. (2016). Osteoblasts Secrete miRNA-Containing Extracellular Vesicles That Enhance Expansion of Human Umbilical Cord Blood Cells. Sci. Rep., 6.","DOI":"10.1038\/srep32034"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1007\/s13770-023-00536-x","article-title":"Development of Matrix Metalloproteinases-Mediated Extracellular Matrix Remodeling in Regenerative Medicine: A Mini Review","volume":"20","author":"Chen","year":"2023","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.eururo.2020.01.012","article-title":"Management of Patients with Advanced Prostate Cancer: Report of the Advanced Prostate Cancer Consensus Conference 2019","volume":"77","author":"Gillessen","year":"2020","journal-title":"Eur. Urol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/0092-8674(82)90409-3","article-title":"Many Tumors Induced by the Mouse Mammary Tumor Virus Contain a Provirus Integrated in the Same Region of the Host Genome","volume":"31","author":"Nusse","year":"1982","journal-title":"Cell"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1038\/nrm3470","article-title":"The Complex World of WNT Receptor Signalling","volume":"13","author":"Niehrs","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.cell.2006.10.018","article-title":"Wnt\/Beta-Catenin Signaling in Development and Disease","volume":"127","author":"Clevers","year":"2006","journal-title":"Cell"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/s41392-024-01937-7","article-title":"Pre-Metastatic Niche: Formation, Characteristics and Therapeutic Implication","volume":"9","author":"Wang","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41392-021-00762-6","article-title":"Wnt\/\u03b2-Catenin Signalling: Function, Biological Mechanisms, and Therapeutic Opportunities","volume":"7","author":"Liu","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Xu, P., Lin, X., and Feng, X.-H. (2016). Posttranslational Regulation of Smads. Cold Spring Harb. Perspect. Biol., 8.","DOI":"10.1101\/cshperspect.a022087"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1089\/ten.teb.2016.0454","article-title":"Osteoblast Differentiation and Bone Matrix Formation In Vivo and In Vitro","volume":"23","author":"Blair","year":"2017","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"\u0160romov\u00e1, V., Sobola, D., and Kaspar, P. (2023). A Brief Review of Bone Cell Function and Importance. Cells, 12.","DOI":"10.3390\/cells12212576"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"112137","DOI":"10.1016\/j.yexcr.2020.112137","article-title":"The PI3K\/AKT Pathway Promotes Fracture Healing through Its Crosstalk with Wnt\/\u03b2-Catenin","volume":"394","author":"Dong","year":"2020","journal-title":"Exp. Cell Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1186\/s13046-024-03207-4","article-title":"AKT Kinases as Therapeutic Targets","volume":"43","author":"Hassan","year":"2024","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.cell.2017.06.009","article-title":"RAS Proteins and Their Regulators in Human Disease","volume":"170","author":"Simanshu","year":"2017","journal-title":"Cell"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1128\/MMBR.00031-10","article-title":"Activation and Function of the MAPKs and Their Substrates, the MAPK-Activated Protein Kinases","volume":"75","author":"Cargnello","year":"2011","journal-title":"Microbiol. Mol. Biol. Rev. MMBR"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1177\/1947601911407328","article-title":"The ERK Cascade: Distinct Functions within Various Subcellular Organelles","volume":"2","author":"Wortzel","year":"2011","journal-title":"Genes Cancer"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/s41392-023-01705-z","article-title":"Targeting the RAS\/RAF\/MAPK Pathway for Cancer Therapy: From Mechanism to Clinical Studies","volume":"8","author":"Bahar","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_86","first-page":"4110","article-title":"Bone Physiological Microenvironment and Healing Mechanism: Basis for Future Bone-Tissue Engineering Scaffolds","volume":"6","author":"Zhu","year":"2021","journal-title":"Bioact. Mater."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Lange, M., Babczyk, P., and Tobiasch, E. (2024). Exosomes: A New Hope for Angiogenesis-Mediated Bone Regeneration. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25105204"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Zhai, Y., Schilling, K., Wang, T., El Khatib, M., Vinogradov, S., Brown, E.B., and Zhang, X. (2021). Spatiotemporal Blood Vessel Specification at the Osteogenesis and Angiogenesis Interface of Biomimetic Nanofiber-Enabled Bone Tissue Engineering. Biomaterials, 276.","DOI":"10.1016\/j.biomaterials.2021.121041"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"De Sousa, K.P., Rossi, I., Abdullahi, M., Ramirez, M.I., Stratton, D., and Inal, J.M. (2023). Isolation and Characterization of Extracellular Vesicles and Future Directions in Diagnosis and Therapy. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol., 15.","DOI":"10.1002\/wnan.1835"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1042\/CS20220531","article-title":"M1\/M2 Macrophages and Their Overlaps\u2014Myth or Reality?","volume":"137","author":"Strizova","year":"2023","journal-title":"Clin. Sci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41392-022-00932-0","article-title":"The Secretion Profile of Mesenchymal Stem Cells and Potential Applications in Treating Human Diseases","volume":"7","author":"Han","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"5763","DOI":"10.2147\/IJN.S518655","article-title":"Macrophage-Derived Extracellular Vesicles: A Novel Therapeutic Alternative for Diabetic Wound","volume":"20","author":"Shi","year":"2025","journal-title":"Int. J. Nanomed."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/mlf2.12167","article-title":"Synthetic Evolution of Saccharomyces Cerevisiae for Biomanufacturing: Approaches and Applications","volume":"4","author":"Wang","year":"2025","journal-title":"mLife"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"tkae062","DOI":"10.1093\/burnst\/tkae062","article-title":"Engineered Extracellular Vesicles for Tissue Repair and Regeneration","volume":"12","author":"Zhang","year":"2024","journal-title":"Burn. Trauma"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Xing, Y., Sun, X., Dou, Y., Wang, M., Zhao, Y., Yang, Q., and Zhao, Y. (2021). The Immuno-Modulation Effect of Macrophage-Derived Extracellular Vesicles in Chronic Inflammatory Diseases. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.785728"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"20417314241286606","DOI":"10.1177\/20417314241286606","article-title":"Exosomal Non-Coding RNAs: Emerging Insights into Therapeutic Potential and Mechanisms in Bone Healing","volume":"15","author":"Shi","year":"2024","journal-title":"J. Tissue Eng."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1186\/s12964-024-01560-7","article-title":"M1-Derived Extracellular Vesicles Polarize Recipient Macrophages into M2-like Macrophages and Alter Skeletal Muscle Homeostasis in a Hyper-Glucose Environment","volume":"22","author":"Tacconi","year":"2024","journal-title":"Cell Commun. Signal. CCS"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Jiang, L., Dong, J., Jiang, M., Tan, W., Zeng, Y., Liu, X., Wang, P., Jiang, H., Zhou, J., and Liu, X. (2025). 3D-Printed Multifunctional Bilayer Scaffold with Sustained Release of Apoptotic Extracellular Vesicles and Antibacterial Coacervates for Enhanced Wound Healing. Biomaterials, 318.","DOI":"10.1016\/j.biomaterials.2025.123196"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1097\/SHK.0000000000001002","article-title":"Fracture Healing and the Underexposed Role of Extracellular Vesicle-Based Cross Talk","volume":"49","author":"Qiao","year":"2018","journal-title":"Shock"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Rozier, P., Maumus, M., Bony, C., Maria, A.T.J., Sabatier, F., Jorgensen, C., Guilpain, P., and No\u00ebl, D. (2021). Extracellular Vesicles Are More Potent Than Adipose Mesenchymal Stromal Cells to Exert an Anti-Fibrotic Effect in an In Vitro Model of Systemic Sclerosis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22136837"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/s00281-018-0682-0","article-title":"Molecular Interactions at the Surface of Extracellular Vesicles","volume":"40","year":"2018","journal-title":"Semin. Immunopathol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"565","DOI":"10.33549\/physiolres.935143","article-title":"Cellular and Molecular Connections Between Bone Fracture Healing and Exosomes","volume":"72","author":"Lv","year":"2023","journal-title":"Physiol. Res."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Mao, B., Zhang, Z., Lai, S., Zhang, K., Li, J., and Fu, W. (2022). Demineralized Cortical Bone Matrix Augmented With Peripheral Blood-Derived Mesenchymal Stem Cells for Rabbit Medial Meniscal Reconstruction. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.855103"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Percival, K.M., Paul, V., and Husseini, G.A. (2024). Recent Advancements in Bone Tissue Engineering: Integrating Smart Scaffold Technologies and Bio-Responsive Systems for Enhanced Regeneration. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25116012"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Gangadaran, P., Onkar, A., Rajendran, R.L., Goenka, A., Oh, J.M., Khan, F., Nagarajan, A.K., Muthu, S., Krishnan, A., and Hong, C.M. (2025). Noninvasive in Vivo Imaging of Macrophages: Understanding Tumor Microenvironments and Delivery of Therapeutics. Biomark. Res., 13.","DOI":"10.1186\/s40364-025-00735-9"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/s41413-023-00313-5","article-title":"The Role and Applications of Extracellular Vesicles in Osteoporosis","volume":"12","author":"Fang","year":"2024","journal-title":"Bone Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"114616","DOI":"10.1016\/j.yexcr.2025.114616","article-title":"Mesenchymal Stem Cell-Derived Exosomes: A Paradigm Shift in Clinical Therapeutics","volume":"450","author":"Chattopadhyay","year":"2025","journal-title":"Exp. Cell Res."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Muraca, M., and Cappariello, A. (2020). The Role of Extracellular Vesicles (EVs) in the Epigenetic Regulation of Bone Metabolism and Osteoporosis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228682"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"7653","DOI":"10.2147\/IJN.S522198","article-title":"Extracellular Vesicle-Integrated Biomaterials in Bone Tissue Engineering Applications: Current Progress and Future Perspectives","volume":"20","author":"Huang","year":"2025","journal-title":"Int. J. Nanomed."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2863","DOI":"10.1002\/jbm.a.36475","article-title":"Hydroxyapatite\/Collagen Coating on PLGA Electrospun Fibers for Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells","volume":"106","author":"Yang","year":"2018","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Jang, H.-J., and Yoon, J.-K. (2024). The Role of Vasculature and Angiogenic Strategies in Bone Regeneration. Biomimetics, 9.","DOI":"10.3390\/biomimetics9020075"},{"key":"ref_112","first-page":"224","article-title":"Bone Grafts and Biomaterials Substitutes for Bone Defect Repair: A Review","volume":"2","author":"Wang","year":"2017","journal-title":"Bioact. Mater."},{"key":"ref_113","first-page":"469","article-title":"Preventing the Rejection of Skin Allografts by Immunomodulatory and Regenerative Effects of Exosomes Derived from Bone Marrow Mesenchymal Stem Cells in Mice","volume":"28","author":"Soufizadeh","year":"2025","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Wang, C., St\u00f6ckl, S., Li, S., Herrmann, M., Lukas, C., Reinders, Y., Sickmann, A., and Gr\u00e4ssel, S. (2022). Effects of Extracellular Vesicles from Osteogenic Differentiated Human BMSCs on Osteogenic and Adipogenic Differentiation Capacity of Na\u00efve Human BMSCs. Cells, 11.","DOI":"10.3390\/cells11162491"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"5047987","DOI":"10.1155\/2020\/5047987","article-title":"ROS-Mediated Therapeutic Strategy in Chemo-\/Radiotherapy of Head and Neck Cancer","volume":"2020","author":"Huang","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.freeradbiomed.2023.06.009","article-title":"Redox-Crippled MitoQ Potently Inhibits Breast Cancer and Glioma Cell Proliferation: A Negative Control for Verifying the Antioxidant Mechanism of MitoQ in Cancer and Other Oxidative Pathologies","volume":"205","author":"Cheng","year":"2023","journal-title":"Free Radic. Biol. Med."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/s13045-022-01313-4","article-title":"Mitochondrial Adaptation in Cancer Drug Resistance: Prevalence, Mechanisms, and Management","volume":"15","author":"Jin","year":"2022","journal-title":"J. Hematol. Oncol."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Liu, Y., Chen, C., Wang, X., Sun, Y., Zhang, J., Chen, J., and Shi, Y. (2022). An Epigenetic Role of Mitochondria in Cancer. Cells, 11.","DOI":"10.3390\/cells11162518"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1186\/s10020-024-01027-y","article-title":"Mitochondrial Uncoupling Protein 2: A Central Player in Pancreatic Disease Pathophysiology","volume":"30","author":"Wang","year":"2024","journal-title":"Mol. Med."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Danilushkina, A.A., Emene, C.C., Barlev, N.A., and Gomzikova, M.O. (2023). Strategies for Engineering of Extracellular Vesicles. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241713247"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"e10476","DOI":"10.1002\/jbm4.10476","article-title":"A Bisphosphonate With a Low Hydroxyapatite Binding Affinity Prevents Bone Loss in Mice After Ovariectomy and Reverses Rapidly With Treatment Cessation","volume":"5","author":"Coffman","year":"2021","journal-title":"JBMR Plus"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.reth.2021.05.006","article-title":"The Promising Rise of Bioprinting in Revolutionalizing Medical Science: Advances and Possibilities","volume":"18","author":"Jamee","year":"2021","journal-title":"Regen. Ther."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Du, S., Guan, Y., Xie, A., Yan, Z., Gao, S., Li, W., Rao, L., Chen, X., and Chen, T. (2023). Extracellular Vesicles: A Rising Star for Therapeutics and Drug Delivery. J. Nanobiotechnol., 21.","DOI":"10.1186\/s12951-023-01973-5"},{"key":"ref_124","first-page":"312","article-title":"Extracellular Vesicles: The Future of Therapeutics and Drug Delivery Systems","volume":"2","author":"Uddin","year":"2024","journal-title":"Intell. Pharm."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.tibtech.2020.05.012","article-title":"Technologies and Standardization in Research on Extracellular Vesicles","volume":"38","author":"Gandham","year":"2020","journal-title":"Trends Biotechnol."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Thakur, A., and Rai, D. (2024). Global Requirements for Manufacturing and Validation of Clinical Grade Extracellular Vesicles. J. Liq. Biopsy, 6.","DOI":"10.1016\/j.jlb.2024.100278"},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Syromiatnikova, V., Prokopeva, A., and Gomzikova, M. (2022). Methods of the Large-Scale Production of Extracellular Vesicles. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231810522"},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Estes, S., Konstantinov, K., and Young, J.D. (2022). Manufactured Extracellular Vesicles as Human Therapeutics: Challenges, Advances, and Opportunities. Curr. Opin. Biotechnol., 77.","DOI":"10.1016\/j.copbio.2022.102776"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"113961","DOI":"10.1016\/j.addr.2021.113961","article-title":"Dosing Extracellular Vesicles","volume":"178","author":"Gupta","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1080\/10717544.2021.1951896","article-title":"Preserving Extracellular Vesicles for Biomedical Applications: Consideration of Storage Stability before and after Isolation","volume":"28","author":"Yuan","year":"2021","journal-title":"Drug Deliv."},{"key":"ref_131","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_132","doi-asserted-by":"crossref","first-page":"e12238","DOI":"10.1002\/jev2.12238","article-title":"Identification of Storage Conditions Stabilizing Extracellular Vesicles Preparations","volume":"11","author":"Corso","year":"2022","journal-title":"J. Extracell. Vesicles"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"e12162","DOI":"10.1002\/jev2.12162","article-title":"The Impact of Storage on Extracellular Vesicles: A Systematic Study","volume":"11","author":"Gelibter","year":"2022","journal-title":"J. Extracell. Vesicles"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"e2403199","DOI":"10.1002\/adma.202403199","article-title":"Immunogenicity of Extracellular Vesicles","volume":"36","author":"Xia","year":"2024","journal-title":"Adv. Mater."},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Condrat, C.E., Varlas, V.N., Duic\u0103, F., Antoniadis, P., Danila, C.A., Cretoiu, D., Suciu, N., Cre\u021boiu, S.M., and Voinea, S.C. (2021). Pregnancy-Related Extracellular Vesicles Revisited. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22083904"},{"key":"ref_136","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_137","doi-asserted-by":"crossref","first-page":"100736","DOI":"10.1016\/j.mtla.2020.100736","article-title":"Biomaterials and Extracellular Vesicles in Cell-Free Therapy for Bone Repair and Regeneration: Future Line of Treatment in Regenerative Medicine","volume":"12","author":"Holkar","year":"2020","journal-title":"Materialia"},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Infante, A., Alcorta-Sevillano, N., Mac\u00edas, I., and Rodr\u00edguez, C.I. (2022). Educating EVs to Improve Bone Regeneration: Getting Closer to the Clinic. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031865"},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Gholami, L., Nooshabadi, V.T., Shahabi, S., Jazayeri, M., Tarzemany, R., Afsartala, Z., and Khorsandi, K. (2021). Extracellular Vesicles in Bone and Periodontal Regeneration: Current and Potential Therapeutic Applications. Cell Biosci., 11.","DOI":"10.1186\/s13578-020-00527-8"},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Youssef, E., Palmer, D., Fletcher, B., and Vaughn, R. (2025). Exosomes in Precision Oncology and Beyond: From Bench to Bedside in Diagnostics and Therapeutics. Cancers, 17.","DOI":"10.20944\/preprints202501.1036.v1"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.reth.2024.06.001","article-title":"Optimizing Mesenchymal Stem Cell Extracellular Vesicles for Chronic Wound Healing: Bioengineering, Standardization, and Safety","volume":"26","author":"Shimizu","year":"2024","journal-title":"Regen. Ther."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"5561","DOI":"10.2147\/IJN.S424731","article-title":"Harnessing Stem Cell-Derived Extracellular Vesicles for the Regeneration of Degenerative Bone Conditions","volume":"18","author":"Jia","year":"2023","journal-title":"Int. J. Nanomed."}],"updated-by":[{"DOI":"10.3390\/cimb48020154","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000}}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/47\/8\/675\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T11:09:42Z","timestamp":1769771382000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/47\/8\/675"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,21]]},"references-count":142,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["cimb47080675"],"URL":"https:\/\/doi.org\/10.3390\/cimb47080675","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,21]]}}}