{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T05:17:32Z","timestamp":1788585452808,"version":"build-2803163510"},"reference-count":145,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Bisphosphonate-related osteonecrosis of the jaw (BRONJ) remains a challenging complication of bisphosphonate therapy because jaw extraction sockets exposed to bisphosphonates represent impaired wound environments rather than ordinary bone defects. This narrative review summarizes clinical, cellular, animal, and biomaterial evidence on the mechanisms that limit BRONJ repair and discusses how these pathological barriers can inform local material design. Current evidence suggests that BRONJ repair is constrained by impaired osteoclast-mediated remodeling, osteocyte and osteoblast dysfunction, oxidative stress, unresolved inflammation, angiogenic insufficiency, microbial challenge, mucosal instability, and changes in bone material properties. Biomaterial strategies investigated to date include local delivery of regenerative factors, restoration of remodeling activity, extracellular vesicles, nucleic acid nanostructures, platelet-derived matrices, antibacterial and ion-releasing hydrogels, angiogenic or lymphangiogenic systems, and mechanically adaptive scaffolds. Most studies remain preclinical and are based on rodent extraction or mandibular defect models, and few establish a direct causal link between a specific material property and durable BRONJ resolution. Future materials should be judged not only by their ability to enhance bone formation, but also by whether they can re-establish a sealed, vascularized, immune-balanced, and remodeling-competent socket capable of sustained jawbone repair.<\/jats:p>","DOI":"10.3390\/biom16091259","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T01:05:26Z","timestamp":1788224726000},"page":"1259","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanism-Oriented Biomaterial Strategies for Bone Regeneration in BRONJ: From Pathological Barriers to Evidence-Matched Repair"],"prefix":"10.3390","volume":"16","author":[{"given":"Aiming","family":"Jiang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu 610041, China"},{"name":"Department of Head and Neck Cancer Surgery, West China School of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juntong","family":"Liao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinyin","family":"Shi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyan","family":"Song","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu 610041, China"},{"name":"Department of Head and Neck Cancer Surgery, West China School of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4838-4319","authenticated-orcid":false,"given":"Sisi","family":"Luo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longjiang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Cancer Surgery, West China School of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuoyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu 610041, China"},{"name":"Department of Head and Neck Cancer Surgery, West China School of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1016\/j.joms.2022.02.008","article-title":"American Association of Oral and Maxillofacial Surgeons\u2019 Position Paper on Medication-Related Osteonecrosis of the Jaws-2022 Update","volume":"80","author":"Ruggiero","year":"2022","journal-title":"J. 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