Smart Implantable Hydrogel for Large Segmental Bone Regeneration

Abstract Large segmental bone defects often lead to nonunion and dysfunction, posing a significant challenge for clinicians. Inspired by the intrinsic bone defect repair logic of “vascularization and then osteogenesis”, this study originally reports a smart implantable hydrogel (PDS‐DC) with high mechanical properties, controllable scaffold degradation, and timing drug release that can proactively match different bone healing cycles to efficiently promote bone regeneration. The main scaffold of PDS‐DC consists of polyacrylamide, polydopamine, and silk fibroin, which endows it with superior interfacial adhesion, structural toughness, and mechanical stiffness. In particular, the adjustment of scaffold cross‐linking agent mixing ratio can effectively regulate the in vivo degradation rate of PDS‐DC and intelligently satisfy the requirements of different bone defect healing cycles. Ultimately, PDS hydrogel loaded with free desferrioxamine (DFO) and CaCO 3 mineralized ZIF‐90 loaded bone morphogenetic protein‐2 (BMP‐2) to stimulate efficient angiogenesis and osteogenesis. Notably, DFO is released rapidly by free diffusion, whereas BMP‐2 is released slowly by pH‐dependent layer‐by‐layer disintegration, resulting in a significant difference in release time, thus matching the intrinsic logic of bone defect repair. In vivo and in vitro results confirm that PDS‐DC can effectively realize high‐quality bone generation and intelligently regulate to adapt to different demands of bone defects.