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However, discrepancies between material degradation rates and the physiological timeline of bone healing remain a critical limitation. Here, a polyurethane-based adhesive (TNC) was developed, synthesized from trimeric hexamethylene diisocyanate, nano-hydroxyapatite, and type I collagen. The TNC demonstrates strong initial adhesion to both wet and blood-contaminated bone surfaces and exhibits excellent biocompatibility. A distinguishing feature of TNC is its capacity to synchronize degradation with the stages of bone healing. During degradation, TNC forms a mineralized surface layer that releases calcium ions. The calcium ions activate cathepsin K, an enzyme integral to bone remodeling. This calcium-mediated mechanism accelerates TNC degradation by 1.9-fold during the remodeling phase compared to the initial phase. In a rat skull fracture model, TNC supported effective fracture stabilization and achieved favorable bone regeneration at 8 weeks after implantation. These findings demonstrate that TNC combines early mechanical stability with phase-specific degradability to facilitate bone regeneration in a temporally-controlled manner. The present work provides a framework for the development of bio-responsive bone adhesives that synchronize degradation behavior with healing phases for orthopedic applications.<\/jats:p>","DOI":"10.1038\/s41413-026-00522-8","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T06:51:55Z","timestamp":1775544715000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Bone adhesive with temporally-synchronized degradation for enhanced osteointegration"],"prefix":"10.1038","volume":"14","author":[{"given":"Jun-ting","family":"Gu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-ting","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-zhu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-xiao","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gao-peng","family":"Dang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Qing","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franklin R.","family":"Tay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-hua","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2969-6067","authenticated-orcid":false,"given":"Conrado","family":"Aparicio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6653-0819","authenticated-orcid":false,"given":"Li-na","family":"Niu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"522_CR1","doi-asserted-by":"publisher","first-page":"1461","DOI":"10.1016\/S0142-9612(98)00059-3","volume":"19","author":"M Donkerwolcke","year":"1998","unstructured":"Donkerwolcke, M., Burny, F. & Muster, D. 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