Micro/Nanobiomimetic Iron-Based Scaffold Induces Vascularized Bone Regeneration To Repair Large Segmental Bone Defect in Load-Bearing Sites

Biodegradable scaffolds, including metals, ceramics, and polymers, show great potential in bone tissue regeneration. However, current biodegradable scaffolds do not simultaneously possess suitable mechanical properties, biodegradability and osteoinductivity, which severely limits their clinical application for large segmental bone defect repair. Herein, we developed a biomimetic and hierarchically micro-nanoporous iron-based scaffold utilizing a synergistic approach combining 3-dimensional printing, surface dealloying treatment and electrochemical deposition. Compared to traditional periodic lattice structures, the biomimetic scaffold with a stochastic lattice structure promised superior stress transfer efficiency. Cell experiments revealed that the biomimetic scaffold notably enhanced osteogenesis and angiogenesis in vitro via EGFR-mediated Ras/Raf/MAPK signaling. Upon implantation in a rat femoral condyle defect model, the scaffold achieved a dynamic equilibrium between in vivo material degradation and bone formation. More importantly, the study conducted in a large animal model with an extended cycle of up to 1 year demonstrated that bionic iron-based scaffolds effectively facilitated the repair and functional reconstruction of large bone defects in load-bearing regions by inducing vascularized bone regeneration. This study not only introduces a potential solution for addressing critical-sized bone defects in load-bearing regions but also provides a viable approach for the design of other biomimetic biomaterials.