{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T17:15:06Z","timestamp":1788974106523,"version":"build-2803163510"},"reference-count":115,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T00:00:00Z","timestamp":1750982400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012151","name":"Sanming Project of Medicine in Shenzen Municipality","doi-asserted-by":"publisher","award":["SZSM202106019"],"award-info":[{"award-number":["SZSM202106019"]}],"id":[{"id":"10.13039\/501100012151","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012151","name":"Sanming Project of Medicine in Shenzen Municipality","doi-asserted-by":"publisher","award":["202208"],"award-info":[{"award-number":["202208"]}],"id":[{"id":"10.13039\/501100012151","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010877","name":"Science, Technology and Innovation Commission of Shenzhen Municipality","doi-asserted-by":"publisher","award":["JCYJ20190809113815103"],"award-info":[{"award-number":["JCYJ20190809113815103"]}],"id":[{"id":"10.13039\/501100010877","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010877","name":"Science, Technology and Innovation Commission of Shenzhen Municipality","doi-asserted-by":"publisher","award":["KCXFZ20240903094059020"],"award-info":[{"award-number":["KCXFZ20240903094059020"]}],"id":[{"id":"10.13039\/501100010877","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Regenerative Therapy"],"published-print":{"date-parts":[[2025,12]]},"DOI":"10.1016\/j.reth.2025.06.020","type":"journal-article","created":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T03:30:03Z","timestamp":1752636603000},"page":"389-402","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":14,"special_numbering":"C","title":["Exosomes promise better bone regeneration"],"prefix":"10.1016","volume":"30","author":[{"given":"Shuaiwen","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7192-8832","authenticated-orcid":false,"given":"Shaogeng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomao","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiguo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohua","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"1","key":"10.1016\/j.reth.2025.06.020_bib1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/jor.24170","article-title":"Cellular biology of fracture healing","volume":"37","author":"Bahney","year":"2019","journal-title":"J Orthop Res"},{"issue":"1","key":"10.1016\/j.reth.2025.06.020_bib2","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/nrrheum.2014.164","article-title":"Fracture healing: mechanisms and interventions","volume":"11","author":"Einhorn","year":"2015","journal-title":"Nat Rev Rheumatol"},{"issue":"22","key":"10.1016\/j.reth.2025.06.020_bib3","doi-asserted-by":"crossref","first-page":"5805","DOI":"10.3390\/ijms20225805","article-title":"Current and future concepts for the treatment of impaired fracture healing","volume":"20","author":"Schlickewei","year":"2019","journal-title":"Int J Mol Sci"},{"issue":"7","key":"10.1016\/j.reth.2025.06.020_bib4","doi-asserted-by":"crossref","first-page":"3183","DOI":"10.7150\/thno.52570","article-title":"Engineering exosomes for targeted drug delivery","volume":"11","author":"Liang","year":"2021","journal-title":"Theranostics"},{"issue":"33","key":"10.1016\/j.reth.2025.06.020_bib5","doi-asserted-by":"crossref","first-page":"36938","DOI":"10.1021\/acsami.0c10458","article-title":"Chondrocyte-rargeted microRNA delivery by engineered exosomes toward a cell-free osteoarthritis therapy","volume":"12","author":"Liang","year":"2020","journal-title":"ACS Appl Mater Interfaces"},{"issue":"11","key":"10.1016\/j.reth.2025.06.020_bib6","doi-asserted-by":"crossref","first-page":"4866","DOI":"10.7150\/thno.69368","article-title":"Chondrocyte-specific genomic editing enabled by hybrid exosomes for osteoarthritis treatment","volume":"12","author":"Liang","year":"2022","journal-title":"Theranostics"},{"issue":"3","key":"10.1016\/j.reth.2025.06.020_bib7","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":"2021","journal-title":"Nanoscale"},{"key":"10.1016\/j.reth.2025.06.020_bib8","doi-asserted-by":"crossref","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":"10.1016\/j.reth.2025.06.020_bib9","doi-asserted-by":"crossref","DOI":"10.1016\/j.mtbio.2023.100760","article-title":"Programming assembly of biomimetic exosomes: An emerging theranostic nanomedicine platform","volume":"22","author":"Xu","year":"2023","journal-title":"Materials Today Bio"},{"issue":"1","key":"10.1016\/j.reth.2025.06.020_bib10","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1186\/s12951-023-02081-0","article-title":"Targeted therapy using engineered extracellular vesicles: principles and strategies for membrane modification","volume":"21","author":"Liu","year":"2023","journal-title":"J Nanobiotechnol"},{"issue":"5","key":"10.1016\/j.reth.2025.06.020_bib11","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1016\/j.ymthe.2022.10.008","article-title":"Cell-derived nanovesicle-mediated drug delivery to the brain: Principles and strategies for vesicle engineering","volume":"31","author":"Liang","year":"2023","journal-title":"Mol Ther"},{"issue":"24","key":"10.1016\/j.reth.2025.06.020_bib12","doi-asserted-by":"crossref","first-page":"3360","DOI":"10.1002\/cbic.202100359","article-title":"Exosomes as Targeted Delivery Platform of CRISPR\/Cas9 for Therapeutic Genome Editing","volume":"22","author":"Duan","year":"2021","journal-title":"ChemBioChem"},{"issue":"11","key":"10.1016\/j.reth.2025.06.020_bib13","doi-asserted-by":"crossref","first-page":"3762","DOI":"10.1039\/D2BM01636B","article-title":"Biomaterial-assisted targeted and controlled delivery of CRISPR\/Cas9 for precise gene editing","volume":"11","author":"Iqbal","year":"2023","journal-title":"Biomater Sci"},{"issue":"42","key":"10.1016\/j.reth.2025.06.020_bib14","first-page":"4536","article-title":"Exosomes and Bone Disease","volume":"25","author":"Su-Kang","year":"2019","journal-title":"Curr Pharm Des"},{"issue":"1","key":"10.1016\/j.reth.2025.06.020_bib15","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s11010-020-03703-z","article-title":"Inside(sight) of tiny communicator: exosome biogenesis, secretion, and uptake","volume":"467","author":"Jadli","year":"2020","journal-title":"Mol Cell Biochem"},{"issue":"3","key":"10.1016\/j.reth.2025.06.020_bib16","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.3390\/ijms22031144","article-title":"Therapeutic application of exosomes in inflammatory diseases","volume":"22","author":"J.H. Suh","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"D1","key":"10.1016\/j.reth.2025.06.020_bib17","doi-asserted-by":"crossref","first-page":"D516","DOI":"10.1093\/nar\/gky1029","article-title":"Vesiclepedia 2019: a compendium of RNA, proteins, lipids and metabolites in extracellular vesicles","volume":"47","author":"Pathan","year":"2018","journal-title":"Nucleic Acids Res"},{"issue":"6478","key":"10.1016\/j.reth.2025.06.020_bib18","doi-asserted-by":"crossref","DOI":"10.1126\/science.aau6977","article-title":"The biology, function, and biomedical applications of exosomes","volume":"367","author":"Kalluri","year":"2020","journal-title":"Science"},{"issue":"12","key":"10.1016\/j.reth.2025.06.020_bib19","doi-asserted-by":"crossref","first-page":"8035","DOI":"10.1002\/jcp.30484","article-title":"Exosomes as drug delivery vehicles and biomarkers for neurological and auditory systems","volume":"236","author":"Mittal","year":"2021","journal-title":"J Cell Physiol"},{"key":"10.1016\/j.reth.2025.06.020_bib20","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.addr.2020.04.004","article-title":"Extracellular vesicles as drug delivery systems: Why and how?","volume":"159","author":"Elsharkasy","year":"2020","journal-title":"Adv Drug Del Rev"},{"key":"10.1016\/j.reth.2025.06.020_bib21","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.3389\/fcell.2018.00018","article-title":"Exosome-based cell-cell communication in the tumor microenvironment","volume":"6","author":"Maia","year":"2018","journal-title":"Front Cell Dev Biol"},{"key":"10.1016\/j.reth.2025.06.020_bib22","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"},{"issue":"3","key":"10.1016\/j.reth.2025.06.020_bib23","doi-asserted-by":"crossref","DOI":"10.1002\/btm2.10492","article-title":"Nanomaterials for mRNA-based therapeutics: Challenges and opportunities","volume":"8","author":"Li","year":"2023","journal-title":"Bioeng Transl Med"},{"issue":"8","key":"10.1016\/j.reth.2025.06.020_bib24","doi-asserted-by":"crossref","DOI":"10.3390\/cells10081959","article-title":"Mesenchymal stem cell-derived exosomes: applications in regenerative medicine","volume":"10","author":"Hade","year":"2021","journal-title":"Cells"},{"issue":"22","key":"10.1016\/j.reth.2025.06.020_bib25","doi-asserted-by":"crossref","first-page":"12204","DOI":"10.3390\/ijms222212204","article-title":"The role of exosomes and their applications in cancer","volume":"22","author":"Zhou","year":"2021","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.reth.2025.06.020_bib26","doi-asserted-by":"crossref","DOI":"10.1016\/j.bone.2020.115627","article-title":"Bone regeneration is mediated by macrophage extracellular vesicles","volume":"141","author":"Kang","year":"2020","journal-title":"Bone"},{"key":"10.1016\/j.reth.2025.06.020_bib27","doi-asserted-by":"crossref","first-page":"409","DOI":"10.3389\/fcell.2020.00409","article-title":"MicroRNAs: From Mechanism to Organism","volume":"8","author":"Dexheimer","year":"2020","journal-title":"Front Cell Dev Biol"},{"issue":"1","key":"10.1016\/j.reth.2025.06.020_bib28","doi-asserted-by":"crossref","first-page":"2783","DOI":"10.1038\/s41467-024-47055-4","article-title":"A lineage-resolved cartography of microRNA promoter activity in C. elegans empowers multidimensional developmental analysis","volume":"15","author":"Xu","year":"2024","journal-title":"Nat Commun"},{"key":"10.1016\/j.reth.2025.06.020_bib29","doi-asserted-by":"crossref","DOI":"10.1016\/j.bone.2020.115758","article-title":"MicroRNAs and fracture healing: Pre-clinical studies","volume":"143","author":"Komatsu","year":"2021","journal-title":"Bone"},{"issue":"4","key":"10.1016\/j.reth.2025.06.020_bib30","doi-asserted-by":"crossref","DOI":"10.1016\/j.injury.2024.111410","article-title":"MicroRNAs in osteoblast differentiation and fracture healing: From pathogenesis to therapeutic implication","volume":"55","author":"Yao","year":"2024","journal-title":"Injury"},{"issue":"2","key":"10.1016\/j.reth.2025.06.020_bib31","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1002\/jbm.a.36824","article-title":"Micro-RNA-incorporated electrospun nanofibers improve osteogenic differentiation of human-induced pluripotent stem cells","volume":"108","author":"Tahmasebi","year":"2020","journal-title":"J Biomed Mater Res A"},{"key":"10.1016\/j.reth.2025.06.020_bib32","doi-asserted-by":"crossref","first-page":"89","DOI":"10.23736\/S0031-0808.19.03669-3","article-title":"MiR-126 affects femoral fracture healing in rats through PI3K\/AKT signaling pathway","volume":"63","author":"Sun","year":"2021","journal-title":"Panminerva Med"},{"key":"10.1016\/j.reth.2025.06.020_bib33","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1016\/j.omtn.2021.02.008","article-title":"miRNA-92a-3p regulates osteoblast differentiation in patients with concomitant limb fractures and TBI via IBSP\/PI3K-AKT inhibition","volume":"23","author":"Hu","year":"2021","journal-title":"Mol Ther Nucleic Acids"},{"issue":"3","key":"10.1016\/j.reth.2025.06.020_bib34","doi-asserted-by":"crossref","DOI":"10.1002\/jev2.12056","article-title":"Exosomes derived from osteogenic tumor activate osteoclast differentiation and concurrently inhibit osteogenesis by transferring COL1A1-targeting miRNA-92a-1-5p","volume":"10","author":"Yu","year":"2021","journal-title":"J Extracell Vesicles"},{"key":"10.1016\/j.reth.2025.06.020_bib35","doi-asserted-by":"crossref","DOI":"10.7717\/peerj.13744","article-title":"BMSC-derived exosomal miR-27a-3p and miR-196b-5p regulate bone remodeling in ovariectomized rats","volume":"10","author":"Lai","year":"2022","journal-title":"PeerJ"},{"issue":"1","key":"10.1016\/j.reth.2025.06.020_bib36","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s12951-020-00622-5","article-title":"Retracted Article: M2 Macrophagy-derived exosomal miRNA-5106 induces bone mesenchymal stem cells towards osteoblastic fate by targeting salt-inducible kinase 2 and 3","volume":"18","author":"Xiong","year":"2020","journal-title":"J Nanobiotechnology"},{"issue":"1","key":"10.1016\/j.reth.2025.06.020_bib37","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1186\/s12951-021-00964-8","article-title":"MiR-144-5p, an exosomal miRNA from bone marrow-derived macrophage in type 2 diabetes, impairs bone fracture healing via targeting Smad1","volume":"19","author":"Zhang","year":"2021","journal-title":"Journal of Nanobiotechnology"},{"issue":"20","key":"10.1016\/j.reth.2025.06.020_bib38","doi-asserted-by":"crossref","DOI":"10.1172\/JCI153644","article-title":"The role of PDGF-BB in the bone-vascular relationship during aging","volume":"131","author":"Zaidi","year":"2021","journal-title":"J. Clin. Invest."},{"issue":"7","key":"10.1016\/j.reth.2025.06.020_bib39","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/s41419-021-03915-1","article-title":"Circ_0008542 in osteoblast exosomes promotes osteoclast-induced bone resorption through m6A methylation","volume":"12","author":"Wang","year":"2021","journal-title":"Cell Death & Disease"},{"issue":"5","key":"10.1016\/j.reth.2025.06.020_bib40","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.3892\/etm.2021.10739","article-title":"Exosomes derived from PC-3 cells suppress osteoclast differentiation by downregulating miR-148a and blocking the PI3K\/AKT\/mTOR pathway","volume":"22","author":"Tian","year":"2021","journal-title":"Exp Ther Med"},{"key":"10.1016\/j.reth.2025.06.020_bib41","doi-asserted-by":"crossref","DOI":"10.1155\/2019\/8650846","article-title":"PC-3-Derived Exosomes Inhibit Osteoclast Differentiation by Downregulating miR-214 and Blocking NF-\u03baB Signaling Pathway","volume":"2019","author":"Duan","year":"2019","journal-title":"Biomed Res Int"},{"key":"10.1016\/j.reth.2025.06.020_bib42","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.jconrel.2023.04.043","article-title":"Osteoclast-targeted delivery of anti-miRNA oligonucleotides by red blood cell extracellular vesicles","volume":"358","author":"Xu","year":"2023","journal-title":"J Control Release"},{"issue":"12","key":"10.1016\/j.reth.2025.06.020_bib43","first-page":"3962","article-title":"Exosomes derived from bone marrow mesenchymal stem cells improve osteoporosis through promoting osteoblast proliferation via MAPK pathway","volume":"22","author":"Zhao","year":"2018","journal-title":"Eur Rev Med Pharmacol Sci"},{"issue":"18","key":"10.1016\/j.reth.2025.06.020_bib44","doi-asserted-by":"crossref","first-page":"3800","DOI":"10.1039\/D1TB00112D","article-title":"Exosomes derived from macrophages upon Zn ion stimulation promote osteoblast and endothelial cell functions","volume":"9","author":"Liu","year":"2021","journal-title":"J Mater Chem B"},{"key":"10.1016\/j.reth.2025.06.020_bib45","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2022.809586","article-title":"The Inhibition of Osteoblast Viability by Monosodium Urate Crystal-Stimulated Neutrophil-Derived Exosomes","volume":"13","author":"Jia","year":"2022","journal-title":"Front Immunol"},{"key":"10.1016\/j.reth.2025.06.020_bib46","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/978-3-319-57613-8_4","article-title":"Endothelial Cells","volume":"1003","author":"Sturtzel","year":"2017","journal-title":"Adv Exp Med Biol"},{"issue":"1","key":"10.1016\/j.reth.2025.06.020_bib47","doi-asserted-by":"crossref","DOI":"10.1080\/20013078.2020.1722385","article-title":"Exosomes derived from HeLa cells break down vascular integrity by triggering endoplasmic reticulum stress in endothelial cells","volume":"9","author":"Lin","year":"2020","journal-title":"J Extracell Vesicles"},{"issue":"7","key":"10.1016\/j.reth.2025.06.020_bib48","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1038\/s41419-021-03986-0","article-title":"Retinoblastoma cell-derived exosomes promote angiogenesis of human vesicle endothelial cells through microRNA-92a-3p","volume":"12","author":"Chen","year":"2021","journal-title":"Cell Death Dis"},{"issue":"9","key":"10.1016\/j.reth.2025.06.020_bib49","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1089\/hum.2010.115","article-title":"Bone marrow mesenchymal stem cells: historical overview and concepts","volume":"21","author":"Charbord","year":"2010","journal-title":"Hum. Gene Ther."},{"issue":"4","key":"10.1016\/j.reth.2025.06.020_bib50","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.gendis.2021.11.012","article-title":"Mesenchymal stromal cell-derived small extracellular vesicles modulate macrophage polarization and enhance angio-osteogenesis to promote bone healing","volume":"9","author":"Chuah","year":"2022","journal-title":"Genes Dis"},{"issue":"16","key":"10.1016\/j.reth.2025.06.020_bib51","doi-asserted-by":"crossref","first-page":"15281","DOI":"10.1021\/acsnano.4c13492","article-title":"Three-Dimensional Bioprinting of Growth Differentiation Factor 5-Preconditioned Mesenchymal Stem Cell-Derived Exosomes Facilitates Articular Cartilage Endogenous Regeneration","volume":"19","author":"Zheng","year":"2025","journal-title":"ACS Nano"},{"issue":"5","key":"10.1016\/j.reth.2025.06.020_bib52","doi-asserted-by":"crossref","DOI":"10.1111\/cpr.12359","article-title":"Stem cell-derived exosomes: A promising strategy for fracture healing","volume":"50","author":"Hao","year":"2017","journal-title":"Cell Prolif"},{"key":"10.1016\/j.reth.2025.06.020_bib53","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.biomaterials.2018.11.007","article-title":"Lithium-containing biomaterials stimulate bone marrow stromal cell-derived exosomal miR-130a secretion to promote angiogenesis","volume":"192","author":"Liu","year":"2019","journal-title":"Biomaterials"},{"issue":"1","key":"10.1016\/j.reth.2025.06.020_bib54","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s12951-020-00601-w","article-title":"Exosomal miRNA-128-3p from mesenchymal stem cells of aged rats regulates osteogenesis and bone fracture healing by targeting Smad5","volume":"18","author":"Xu","year":"2020","journal-title":"J Nanobiotechnology"},{"key":"10.1016\/j.reth.2025.06.020_bib55","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.actbio.2019.12.020","article-title":"Hypoxic mesenchymal stem cell-derived exosomes promote bone fracture healing by the transfer of miR-126","volume":"103","author":"Liu","year":"2020","journal-title":"Acta Biomater"},{"issue":"7","key":"10.1016\/j.reth.2025.06.020_bib56","doi-asserted-by":"crossref","first-page":"836","DOI":"10.7150\/ijbs.14809","article-title":"Exosomes Secreted by Human-Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells Repair Critical-Sized Bone Defects through Enhanced Angiogenesis and Osteogenesis in Osteoporotic Rats","volume":"12","author":"Qi","year":"2016","journal-title":"Int J Biol Sci"},{"issue":"1","key":"10.1016\/j.reth.2025.06.020_bib57","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"},{"issue":"6","key":"10.1016\/j.reth.2025.06.020_bib58","doi-asserted-by":"crossref","first-page":"5240","DOI":"10.1021\/acsami.7b17620","article-title":"Tissue-Engineered Bone Immobilized with Human Adipose Stem Cells-Derived Exosomes Promotes Bone Regeneration","volume":"10","author":"Li","year":"2018","journal-title":"ACS Appl Mater Interfaces"},{"issue":"2","key":"10.1016\/j.reth.2025.06.020_bib59","doi-asserted-by":"crossref","DOI":"10.1111\/cpr.12570","article-title":"Exosomes from human umbilical cord mesenchymal stem cells enhance fracture healing through HIF-1\u03b1-mediated promotion of angiogenesis in a rat model of stabilized fracture","volume":"52","author":"Zhang","year":"2019","journal-title":"Cell Prolif"},{"issue":"11","key":"10.1016\/j.reth.2025.06.020_bib60","first-page":"4954","article-title":"Effects of human umbilical cord mesenchymal stem cells-derived exosomes on fracture healing in rats through the Wnt signaling pathway","volume":"23","author":"Zhou","year":"2019","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"10.1016\/j.reth.2025.06.020_bib61","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.addr.2017.04.012","article-title":"Harnessing macrophage plasticity for tissue regeneration","volume":"114","author":"Smith","year":"2017","journal-title":"Adv Drug Deliv Rev"},{"issue":"4","key":"10.1016\/j.reth.2025.06.020_bib62","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1007\/s13105-018-0622-4","article-title":"Effects of exosomes from LPS-activated macrophages on adipocyte gene expression, differentiation, and insulin-dependent glucose uptake","volume":"74","author":"De Silva","year":"2018","journal-title":"J Physiol Biochem"},{"key":"10.1016\/j.reth.2025.06.020_bib63","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/j.actbio.2019.01.006","article-title":"Exosome-integrated titanium oxide nanotubes for targeted bone regeneration","volume":"86","author":"Wei","year":"2019","journal-title":"Acta Biomater"},{"key":"10.1016\/j.reth.2025.06.020_bib64","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.bone.2014.09.017","article-title":"Bringing new life to damaged bone: the importance of angiogenesis in bone repair and regeneration","volume":"70","author":"Stegen","year":"2015","journal-title":"Bone"},{"key":"10.1016\/j.reth.2025.06.020_bib65","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2024.116343","article-title":"Exosomal hsa_circ_0093884 derived from endothelial progenitor cells promotes therapeutic neovascularization via miR-145\/SIRT1 pathway","volume":"173","author":"Zhao","year":"2024","journal-title":"Biomed Pharmacother"},{"issue":"6","key":"10.1016\/j.reth.2025.06.020_bib66","doi-asserted-by":"crossref","first-page":"3843","DOI":"10.1111\/jcmm.14228","article-title":"EPC-derived exosomes promote osteoclastogenesis through LncRNA-MALAT1","volume":"23","author":"Cui","year":"2019","journal-title":"J. Cell. Mol. Med."},{"issue":"1","key":"10.1016\/j.reth.2025.06.020_bib67","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s13287-018-1115-7","article-title":"Exosomes secreted by endothelial progenitor cells accelerate bone regeneration during distraction osteogenesis by stimulating angiogenesis","volume":"10","author":"Jia","year":"2019","journal-title":"Stem Cell Res Ther"},{"key":"10.1016\/j.reth.2025.06.020_bib68","first-page":"300","article-title":"Exosomal PD-L1 induces osteogenic differentiation and promotes fracture healing by acting as an immunosuppressant","volume":"13","author":"Lin","year":"2022","journal-title":"Bioact Mater"},{"issue":"1","key":"10.1016\/j.reth.2025.06.020_bib69","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1021\/acsnano.1c08284","article-title":"Osteoblast\/osteoclast and immune cocktail therapy of an exosome\/drug delivery multifunctional hydrogel accelerates fracture repair","volume":"16","author":"Mi","year":"2022","journal-title":"ACS Nano"},{"issue":"1","key":"10.1016\/j.reth.2025.06.020_bib70","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1186\/s13287-018-1047-2","article-title":"Exosomes derived from mature chondrocytes facilitate subcutaneous stable ectopic chondrogenesis of cartilage progenitor cells","volume":"9","author":"Chen","year":"2018","journal-title":"Stem Cell Res Ther"},{"issue":"1","key":"10.1016\/j.reth.2025.06.020_bib71","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.bbrc.2015.09.135","article-title":"Identification and proteomic analysis of osteoblast-derived exosomes","volume":"467","author":"Ge","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"issue":"1","key":"10.1016\/j.reth.2025.06.020_bib72","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1002\/1873-3468.12024","article-title":"Exosomes derived from mineralizing osteoblasts promote ST2 cell osteogenic differentiation by alteration of microRNA expression","volume":"590","author":"Cui","year":"2016","journal-title":"FEBS Lett"},{"key":"10.1016\/j.reth.2025.06.020_bib73","doi-asserted-by":"crossref","DOI":"10.3389\/fbioe.2020.615520","article-title":"Influence of Extracellular Vesicles Isolated From Osteoblasts of Patients With Cox-Arthrosis and\/or Osteoporosis on Metabolism and Osteogenic Differentiation of BMSCs","volume":"8","author":"Niedermair","year":"2020","journal-title":"Front Bioeng Biotechnol"},{"issue":"8","key":"10.1016\/j.reth.2025.06.020_bib74","doi-asserted-by":"crossref","first-page":"R435","DOI":"10.1016\/j.cub.2018.01.059","article-title":"Exosomes and Ectosomes in Intercellular Communication","volume":"28","author":"Meldolesi","year":"2018","journal-title":"Curr Biol"},{"issue":"5","key":"10.1016\/j.reth.2025.06.020_bib75","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1038\/s12276-021-00631-w","article-title":"miR-19b enhances osteogenic differentiation of mesenchymal stem cells and promotes fracture healing through the WWP1\/Smurf2-mediated KLF5\/\u03b2-catenin signaling pathway","volume":"53","author":"Huang","year":"2021","journal-title":"Exp Mol Med"},{"issue":"4","key":"10.1016\/j.reth.2025.06.020_bib76","doi-asserted-by":"crossref","first-page":"9901","DOI":"10.1080\/21655979.2022.2062183","article-title":"Human umbilical cord mesenchymal stromal cells promotes the proliferation and osteogenic differentiation of autologous bone marrow stem cells by secreting exosomes","volume":"13","author":"Hai","year":"2022","journal-title":"Bioengineered"},{"key":"10.1016\/j.reth.2025.06.020_bib77","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.omtn.2019.06.001","article-title":"miRNA-26a-5p Accelerates Healing via Downregulation of PTEN in Fracture Patients with Traumatic Brain Injury","volume":"17","author":"Xiong","year":"2019","journal-title":"Mol Ther Nucleic Acids"},{"issue":"3","key":"10.1016\/j.reth.2025.06.020_bib78","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/s12276-023-00956-8","article-title":"Circulating MiRNA-21-enriched extracellular vesicles promote bone remodeling in traumatic brain injury patients","volume":"55","author":"Lin","year":"2023","journal-title":"Exp Mol Med"},{"issue":"3","key":"10.1016\/j.reth.2025.06.020_bib79","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1055\/s-0041-1740380","article-title":"Delayed Fracture Healing","volume":"26","author":"Mick","year":"2022","journal-title":"Semin Musculoskelet Radiol"},{"issue":"1","key":"10.1016\/j.reth.2025.06.020_bib80","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1186\/s13287-022-02823-1","article-title":"Exosomes from adipose-derived stem cells regulate M1\/M2 macrophage phenotypic polarization to promote bone healing via miR-451a\/MIF","volume":"13","author":"Li","year":"2022","journal-title":"Stem Cell Res Ther"},{"key":"10.1016\/j.reth.2025.06.020_bib81","first-page":"460","article-title":"Multifunctional hydrogel enhances bone regeneration through sustained release of Stromal Cell-Derived Factor-1\u03b1 and exosomes","volume":"25","author":"Chen","year":"2023","journal-title":"Bioact Mater"},{"issue":"5","key":"10.1016\/j.reth.2025.06.020_bib82","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/s11914-015-0286-8","article-title":"Diabetes and Its Effect on Bone and Fracture Healing","volume":"13","author":"Jiao","year":"2015","journal-title":"Curr Osteoporos Rep"},{"key":"10.1016\/j.reth.2025.06.020_bib83","first-page":"273","article-title":"M2 macrophage-derived exosomes promote diabetic fracture healing by acting as an immunomodulator","volume":"28","author":"Wang","year":"2023","journal-title":"Bioact Mater"},{"issue":"5","key":"10.1016\/j.reth.2025.06.020_bib84","doi-asserted-by":"crossref","DOI":"10.3390\/ijms24054852","article-title":"Exosomes Derived from Adipose Stem Cells Enhance Bone Fracture Healing via the Activation of the Wnt3a\/\u03b2-Catenin Signaling Pathway in Rats with Type 2 Diabetes Mellitus","volume":"24","author":"Zhang","year":"2023","journal-title":"Int J Mol Sci"},{"issue":"10","key":"10.1016\/j.reth.2025.06.020_bib85","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1093\/gerona\/glt093","article-title":"Public health impact of osteoporosis","volume":"68","author":"Cauley","year":"2013","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"10.1016\/j.reth.2025.06.020_bib86","article-title":"MicroRNAs in Serum Exosomes as Circulating Biomarkers for Postmenopausal Osteoporosis","volume":"13","author":"Shi","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"1","key":"10.1016\/j.reth.2025.06.020_bib87","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1186\/s13287-021-02449-9","article-title":"Serum exosomes from young rats improve the reduced osteogenic differentiation of BMSCs in aged rats with osteoporosis after fatigue loading in vivo","volume":"12","author":"Xun","year":"2021","journal-title":"Stem Cell Res Ther"},{"issue":"6","key":"10.1016\/j.reth.2025.06.020_bib88","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1056\/NEJM199802053380614","article-title":"Pathologic fracture","volume":"338","author":"Wilson","year":"1998","journal-title":"N Engl J Med"},{"issue":"11","key":"10.1016\/j.reth.2025.06.020_bib89","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1002\/jcb.30127","article-title":"Exosomal tumor necrosis factor-\u03b1 from hepatocellular cancer cells (Huh-7) promote osteoclast differentiation","volume":"122","author":"Li","year":"2021","journal-title":"J Cell Biochem"},{"issue":"7","key":"10.1016\/j.reth.2025.06.020_bib90","doi-asserted-by":"crossref","first-page":"8824","DOI":"10.1021\/acsami.2c18308","article-title":"Exosome-Functionalized, Drug-Laden Bone Substitute along with an Antioxidant Herbal Membrane for Bone and Periosteum Regeneration in Bone Sarcoma","volume":"15","author":"Gupta","year":"2023","journal-title":"ACS Appl Mater Interfaces"},{"key":"10.1016\/j.reth.2025.06.020_bib91","doi-asserted-by":"crossref","DOI":"10.3402\/jev.v3.26913","article-title":"Minimal experimental requirements for definition of extracellular vesicles and their functions: a position statement from the International Society for Extracellular Vesicles","volume":"3","author":"L\u00f6tvall","year":"2014","journal-title":"J Extracell Vesicles"},{"issue":"2","key":"10.1016\/j.reth.2025.06.020_bib92","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1002\/jps.24251","article-title":"Quantitative analysis of tissue distribution of the B16BL6-derived exosomes using a streptavidin-lactadherin fusion protein and iodine-125-labeled biotin derivative after intravenous injection in mice","volume":"104","author":"Morishita","year":"2015","journal-title":"J Pharm Sci"},{"key":"10.1016\/j.reth.2025.06.020_bib93","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.jconrel.2022.05.027","article-title":"Exosomes: Large-scale production, isolation, drug loading efficiency, and biodistribution and uptake","volume":"347","author":"Kimiz-Gebologlu","year":"2022","journal-title":"J Control Release"},{"issue":"169","key":"10.1016\/j.reth.2025.06.020_bib94","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1097\/00003086-198209000-00014","article-title":"Biomechanics of pathologic fractures","author":"Pugh","year":"1982","journal-title":"Clin Orthop Relat Res"},{"issue":"5","key":"10.1016\/j.reth.2025.06.020_bib95","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s001980050161","article-title":"Importance of preclinical studies in the development of drugs for treatment of osteoporosis: a review related to the 1998 WHO guidelines","volume":"9","author":"Bonjour","year":"1999","journal-title":"Osteoporos Int"},{"issue":"4","key":"10.1016\/j.reth.2025.06.020_bib96","first-page":"207","article-title":"[Pathologic fractures: diagnostic and therapeutic considerations and results of treatment]","volume":"380","author":"Maurer","year":"1995","journal-title":"Langenbecks Arch Chir"},{"issue":"1","key":"10.1016\/j.reth.2025.06.020_bib97","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/cdd.2014.130","article-title":"Exosomes as divine messengers: are they the Hermes of modern molecular oncology?","volume":"22","author":"Braicu","year":"2015","journal-title":"Cell Death Differ"},{"key":"10.1016\/j.reth.2025.06.020_bib98","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jot.2018.05.002","article-title":"Molecular pathogenesis of fracture nonunion","volume":"14","author":"Ding","year":"2018","journal-title":"J Orthop Translat"},{"key":"10.1016\/j.reth.2025.06.020_bib99","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.ceb.2014.05.004","article-title":"Biogenesis and secretion of exosomes","volume":"29","author":"Kowal","year":"2014","journal-title":"Curr Opin Cell Biol"},{"issue":"10","key":"10.1016\/j.reth.2025.06.020_bib100","doi-asserted-by":"crossref","DOI":"10.3390\/ijms25105204","article-title":"Exosomes: A new hope for angiogenesis-mediated bone regeneration","volume":"25","author":"Lange","year":"2024","journal-title":"Int J Mol Sci"},{"issue":"5","key":"10.1016\/j.reth.2025.06.020_bib101","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"},{"issue":"7492","key":"10.1016\/j.reth.2025.06.020_bib102","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1038\/nature13146","article-title":"Endothelial Notch activity promotes angiogenesis and osteogenesis in bone","volume":"507","author":"Ramasamy","year":"2014","journal-title":"Nature"},{"issue":"8","key":"10.1016\/j.reth.2025.06.020_bib103","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1111\/os.14131","article-title":"Immunomodulation pathogenesis and treatment of bone nonunion","volume":"16","author":"Song","year":"2024","journal-title":"Orthop Surg"},{"issue":"2","key":"10.1016\/j.reth.2025.06.020_bib104","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.rbo.2015.03.009","article-title":"For the first fracture to be the last","volume":"51","author":"Stolnicki","year":"2016","journal-title":"Rev Bras Ortop"},{"issue":"9","key":"10.1016\/j.reth.2025.06.020_bib105","first-page":"1130","article-title":"Effectiveness of percutaneous injection of autologous concentrated bone marrow aspirate combined with platelet-rich plasma in treatment of delayed fracture healing","volume":"34","author":"Tang","year":"2020","journal-title":"Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi"},{"issue":"1","key":"10.1016\/j.reth.2025.06.020_bib106","doi-asserted-by":"crossref","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":"Th\u00e9ry","year":"2018","journal-title":"J Extracell Vesicles"},{"issue":"6","key":"10.1016\/j.reth.2025.06.020_bib107","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"},{"issue":"5","key":"10.1016\/j.reth.2025.06.020_bib108","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/s41580-022-00460-3","article-title":"Challenges and directions in studying cell-cell communication by extracellular vesicles","volume":"23","author":"van Niel","year":"2022","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"10","key":"10.1016\/j.reth.2025.06.020_bib109","doi-asserted-by":"crossref","first-page":"E828","DOI":"10.1152\/ajpendo.00056.2016","article-title":"The effects of microvesicles on endothelial progenitor cells are compromised in type 2 diabetic patients via downregulation of the miR-126\/VEGFR2 pathway","volume":"310","author":"Wu","year":"2016","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"5","key":"10.1016\/j.reth.2025.06.020_bib110","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1002\/term.2652","article-title":"Simvastatin improves oral implant osseointegration via enhanced autophagy and osteogenesis of BMSCs and inhibited osteoclast activity","volume":"12","author":"Xu","year":"2018","journal-title":"J Tissue Eng Regen Med"},{"issue":"4","key":"10.1016\/j.reth.2025.06.020_bib111","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1007\/s12031-015-0539-0","article-title":"Buyang Huanwu Decoction (BYHWD) Enhances Angiogenic Effect of Mesenchymal Stem Cell by Upregulating VEGF Expression After Focal Cerebral Ischemia","volume":"56","author":"Yang","year":"2015","journal-title":"J Mol Neurosci"},{"key":"10.1016\/j.reth.2025.06.020_bib112","doi-asserted-by":"crossref","DOI":"10.3389\/fmolb.2024.1268019","article-title":"Therapeutic potential of mesenchymal stem cell-derived exosomes in skeletal diseases","volume":"11","author":"Yang","year":"2024","journal-title":"Front Mol Biosci"},{"issue":"1","key":"10.1016\/j.reth.2025.06.020_bib113","doi-asserted-by":"crossref","DOI":"10.2106\/JBJS.RVW.O.00008","article-title":"Biological Risk Factors for Nonunion of Bone Fracture","volume":"4","author":"Zura","year":"2016","journal-title":"JBJS Rev"},{"issue":"3","key":"10.1016\/j.reth.2025.06.020_bib114","doi-asserted-by":"crossref","first-page":"593","DOI":"10.5187\/jast.2021.e39","article-title":"Comparative analysis of dietary exosome-derived microRNAs from human, bovine and caprine colostrum and mature milk","volume":"63","author":"Yun","year":"2021","journal-title":"J Anim Sci Technol"},{"issue":"12","key":"10.1016\/j.reth.2025.06.020_bib115","doi-asserted-by":"crossref","first-page":"4267","DOI":"10.1002\/jcb.26077","article-title":"Exosomes Transfer Among Different Species Cells and Mediating miRNAs Delivery","volume":"118","author":"Zhou","year":"2017","journal-title":"J. Cell. Biochem."}],"container-title":["Regenerative Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2352320425001531?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2352320425001531?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T19:22:46Z","timestamp":1778872966000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2352320425001531"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":115,"alternative-id":["S2352320425001531"],"URL":"https:\/\/doi.org\/10.1016\/j.reth.2025.06.020","relation":{},"ISSN":["2352-3204"],"issn-type":[{"value":"2352-3204","type":"print"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Exosomes promise better bone regeneration","name":"articletitle","label":"Article Title"},{"value":"Regenerative Therapy","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.reth.2025.06.020","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Author(s). Published by Elsevier BV on behalf of The Japanese Society for Regenerative Medicine.","name":"copyright","label":"Copyright"}]}}