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To address these issues, it develops a trifunctional hydrogel (SF\u2010ZIF@NA) designed to selectively inhibit osteoclast activity and enhance vascularized bone regeneration. By enzymatically removing sialic acid, SF\u2010ZIF@NA prevents precursor osteoclasts (pOCs) from fusing into bone\u2010resorbing mature osteoclasts (mOCs), thereby preserving pOCs and their anabolic functions. Additionally, the hydrogel releases Zinc ion (Zn\n                    <jats:sup>2<\/jats:sup>\n                    \u207a) in response to acidic conditions, promoting osteogenesis and angiogenesis. In vitro results confirmed that SF\u2010ZIF@NA impedes osteoclast fusion, enhances platelet\u2010derived growth factor\u2010BB (PDGF\u2010BB secretion from pOCs, and activates the FAK (focal adhesion kinase) signaling pathway to stimulate vascularized bone formation. In osteoporotic bone defect models, SF\u2010ZIF@NA accelerated bone repair with increased bone density and vascularization. These findings demonstrate that SF\u2010ZIF@NA offers a targeted and multifunctional strategy for osteoporotic bone regeneration by concurrently modulating osteoclast activity and promoting angiogenesis.\n                  <\/jats:p>","DOI":"10.1002\/advs.202415895","type":"journal-article","created":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T04:27:30Z","timestamp":1743222450000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Trifunctional Sialylation\u2010Based SF\u2010ZIF@NA Hydrogel for Selective Osteoclast Inhibition and Enhanced Bone\u2010Vessel Regeneration in Osteoporotic Bone Defects"],"prefix":"10.1002","volume":"12","author":[{"given":"Zhengrong","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Orthopedics Southwest Hospital Third Military Medical University (Army Medical University)  Chongqing 400038 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