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These nerve fibers, in addition to transmitting information within the bone and mediating bone sensations, play a crucial role in regulating bone tissue formation and regeneration. Traditional bone tissue engineering (BTE) often fails to achieve satisfactory outcomes when dealing with large-scale bone defects, which is frequently related to the lack of effective reconstruction of the neurovascular network. In recent years, increasing research has revealed the critical role of nerves in bone metabolism. Nerve fibers regulate bone cells through neurotransmitters, neuropeptides, and peripheral glial cells. Furthermore, nerves also coordinate with the vascular and immune systems to jointly construct a microenvironment favorable for bone regeneration. As a signaling driver of bone formation, neuroregulation spans the entire process of bone physiological activities from the embryonic formation to postmaturity remodeling and repair. However, there is currently a lack of comprehensive summaries of these regulatory mechanisms. Therefore, this review sketches out the function of nerves during bone formation and regeneration. Then, we elaborate on the mechanisms of neurovascular coupling and neuromodulation of bone immunity. Finally, we discuss several novel strategies for neuro-bone tissue engineering (NBTE) based on neuroregulation of bone, focusing on the coordinated regeneration of nerve and bone tissue.<\/jats:p>","DOI":"10.1021\/acsami.4c16786","type":"journal-article","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T09:54:57Z","timestamp":1737971697000},"page":"7223-7250","source":"Crossref","is-referenced-by-count":19,"title":["Neuroregulation\nduring\nBone Formation and Regeneration:\nMechanisms and Strategies"],"prefix":"10.1021","volume":"17","author":[{"given":"Xiangrong","family":"Zhao","sequence":"first","affiliation":[{"name":"West China Hospital of Stomatology, Med-X Center for Materials, Sichuan University , , , ,","place":["Chengdu, Sichuan, China, 610041"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meilin","family":"Yao","sequence":"additional","affiliation":[{"name":"West China Hospital of Stomatology, Med-X Center for Materials, Sichuan University , , , ,","place":["Chengdu, Sichuan, China, 610041"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyi","family":"Wang","sequence":"additional","affiliation":[{"name":"Sichuan University , , ,","place":["Chengdu, China, 610064"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Feng","sequence":"additional","affiliation":[{"name":"Sichuan University , , ,","place":["Chengdu, China, 610064"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhan","family":"Yang","sequence":"additional","affiliation":[{"name":"West China Hospital of Stomatology, Med-X Center for Materials, Sichuan University , , , ,","place":["Chengdu, Sichuan, China, 610041"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luoqiang","family":"Tian","sequence":"additional","affiliation":[{"name":"Sichuan University , , ,","place":["Chengdu, China, 610064"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2232-184X","authenticated-orcid":true,"given":"Chongyun","family":"Bao","sequence":"additional","affiliation":[{"name":"West China Hospital of Stomatology, Med-X Center for Materials, Sichuan University , , , ,","place":["Chengdu, Sichuan, China, 610041"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7400-9900","authenticated-orcid":true,"given":"Xiangfeng","family":"Li","sequence":"additional","affiliation":[{"name":"Sichuan University , , ,","place":["Chengdu, China, 610064"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangdong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Sichuan University , , ,","place":["Chengdu, China, 610064"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingdong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Sichuan University , , ,","place":["Chengdu, China, 610064"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2025,1,27]]},"reference":[{"issue":"2","key":"2026090711094847700_cit1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0040009","article-title":"Cell-based\nbone tissue engineering","volume":"4","author":"Meijer","year":"2007","journal-title":"PLoS medicine"},{"key":"2026090711094847700_cit2","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.bioactmat.2022.08.001","article-title":"Advanced Hydrogel systems for mandibular\nreconstruction","volume":"21","author":"Guo","year":"2023","journal-title":"Bioactive materials"},{"issue":"31","key":"2026090711094847700_cit3","doi-asserted-by":"publisher","first-page":"13614","DOI":"10.1073\/pnas.1003600107","article-title":"Osteoinductive\nceramics as a synthetic alternative\nto autologous bone grafting","volume":"107","author":"Yuan","year":"2010","journal-title":"Proc. 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