High‐Performance Prevascularized SHED‐Laden rGO@Hydrogel Achieves Optimized Diabetic Bone Defect Repair

ABSTRACT Diabetic bone defects repair is severely hindered by impaired angiogenesis and delayed osteogenesis. Conventional tissue‐engineered scaffolds often fail to achieve effective vascularization due to the compromised angiogenic capacity of host endothelial cells in the hyperglycemic microenvironment. Here, we developed a prevascularized scaffold by encapsulating stem cells from human exfoliated deciduous teeth (SHED), which shared developmental origin to craniofacial bone, within a reduced graphene oxide (rGO)‐integrated hydrogel. rGO significantly accelerated SHED‐mediated formation of vascular networks in vitro. The scaffold's therapeutic efficacy was confirmed in a clinically relevant diabetic beagle dog mandibular defect model, which showed increased vascular density and accelerated bone regeneration. Mechanistic validation revealed that rGO activates the FAK‐Src/RELA pathway to upregulate P4HA1, subsequently enhancing collagen I synthesis and driving extracellular matrix (ECM) remodeling to create a pro‐angiogenic niche. This study demonstrates that engineering the ECM with rGO is a novel strategy to accelerate prevascularization and bone repair in diabetic conditions.