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.