Trifunctional Sialylation-Based SF-ZIF@NA Hydrogel for Selective Osteoclast Inhibition and Enhanced Bone-Vessel...

Osteoporotic bone defects are challenging to repair due to imbalances in bone resorption and formation, coupled with insufficient vascularization. To address these issues, it develops a trifunctional hydrogel (SF-ZIF@NA) designed to selectively inhibit osteoclast activity and enhance vascularized bone regeneration. By enzymatically removing sialic acid, SF-ZIF@NA prevents precursor osteoclasts (pOCs) from fusing into bone-resorbing mature osteoclasts (mOCs), thereby preserving pOCs and their anabolic functions. Additionally, the hydrogel releases Zinc ion (Zn²⁺) in response to acidic conditions, promoting osteogenesis and angiogenesis. In vitro results confirmed that SF-ZIF@NA impedes osteoclast fusion, enhances platelet-derived growth factor-BB (PDGF-BB secretion from pOCs, and activates the FAK (focal adhesion kinase) signaling pathway to stimulate vascularized bone formation. In osteoporotic bone defect models, SF-ZIF@NA accelerated bone repair with increased bone density and vascularization. These findings demonstrate that SF-ZIF@NA offers a targeted and multifunctional strategy for osteoporotic bone regeneration by concurrently modulating osteoclast activity and promoting angiogenesis.