{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:02:26Z","timestamp":1790776946810,"version":"4.1.0"},"reference-count":74,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Zhejiang Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["LTGD23C100001"],"award-info":[{"award-number":["LTGD23C100001"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"award":["LTGD23C100001"],"award-info":[{"award-number":["LTGD23C100001"]}],"id":[{"id":"https:\/\/ror.org\/04aqat463","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011493","name":"Taizhou Municipal Science and Technology Bureau","doi-asserted-by":"publisher","award":["25nya18"],"award-info":[{"award-number":["25nya18"]}],"id":[{"id":"10.13039\/501100011493","id-type":"DOI","asserted-by":"publisher"}]},{"award":["25nya18"],"award-info":[{"award-number":["25nya18"]}],"id":[{"id":"https:\/\/ror.org\/041fzeq08","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Polymers"],"abstract":"<jats:p>Critical-sized bone defects lack spontaneous healing capacity. While mesenchymal stem cell-derived exosomes (sEVs) are promising osteoinductive agents, their rapid in vivo clearance limits their free-form efficacy. Here, we fabricated a nano-hydroxyapatite\/chitosan (nHA\/CTS) composite scaffold as a protective, sustained-delivery platform for human umbilical cord blood-derived mesenchymal stem cell exosomes (HUCB-MSCs-exos) to accelerate bone repair. The 3D porous CTS\/10% nHA scaffold exhibited excellent cytocompatibility and a degradation rate commensurate with new bone ingrowth. Critically, it enabled a biphasic exosome release profile\u2014an initial burst followed by a 14-day sustained release (89.73% cumulative release). In vitro, HUCB-MSCs-exos significantly promoted the proliferation, migration, and osteogenic differentiation of bone marrow-derived MSCs, as demonstrated by enhanced alkaline phosphatase activity and matrix mineralization. In a rabbit condylar defect model (5 mm diameter), the CTS\/10% nHA-exo scaffold achieved a 57.44 \u00b1 8.42% healing rate at two months, nearly two-fold greater than the scaffold-only group (29.33 \u00b1 6.94%). Histological and immunohistochemical analyses at two months confirmed the formation of mature, well-vascularized trabecular bone, accompanied by robust expression of late-stage osteogenic markers (OCN and OPN). These findings demonstrate that the CTS\/10% nHA scaffold synergistically integrates osteoconductive structural guidance with exosome-mediated osteoinductive paracrine signaling, providing a compelling and translatable strategy for critical-sized bone-defect management.<\/jats:p>","DOI":"10.3390\/polym18131562","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T17:11:49Z","timestamp":1782234709000},"page":"1562","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Enhanced Bone-Defect Regeneration Through nHA\/Chitosan Nanocomposite-Facilitated Delivery of HUCB-MSCs-Derived Exosomes"],"prefix":"10.3390","volume":"18","author":[{"given":"Lingzhi","family":"Ding","sequence":"first","affiliation":[{"name":"Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiachen","family":"Liu","sequence":"additional","affiliation":[{"name":"Taizhou Key Laboratory of Biomass Functional Materials Development and Application, School of Life Science, Taizhou University, Taizhou 318000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Gao","sequence":"additional","affiliation":[{"name":"Taizhou Key Laboratory of Biomass Functional Materials Development and Application, School of Life Science, Taizhou University, Taizhou 318000, China"},{"name":"College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211816, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqian","family":"Fu","sequence":"additional","affiliation":[{"name":"Taizhou Key Laboratory of Biomass Functional Materials Development and Application, School of Life Science, Taizhou University, Taizhou 318000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7694-8249","authenticated-orcid":false,"given":"Wenhui","family":"Chu","sequence":"additional","affiliation":[{"name":"Taizhou Key Laboratory of Biomass Functional Materials Development and Application, School of Life Science, Taizhou University, Taizhou 318000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunwu","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1186\/s40001-021-00593-9","article-title":"Strategies for large bone defect reconstruction after trauma, infections or tumour excision: A comprehensive review of the literature","volume":"26","author":"Migliorini","year":"2021","journal-title":"Eur. 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