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

Background
In diabetic bone defects, impaired angiogenesis and delayed osteogenesis limit regeneration. Host endothelial cells under high-glucose conditions often fail to build stable vessels, so conventional scaffolds struggle to achieve effective vascularization. The targeting focus is prevascularization: forming a microvascular network ex vivo before implantation, then allowing rapid connection with host circulation. SHED are attractive seed cells because of their craniofacial developmental origin, high proliferation, low immunogenicity, and pro-angiogenic potential. However, SHED-based vascular network formation usually takes weeks, which remains a practical bottleneck.

Innovation
This work encapsulates SHED in an rGO@hydrogel to build a prevascularized scaffold. rGO markedly accelerates SHED-mediated vascular network formation in vitro. In a diabetic beagle mandibular defect model, the scaffold group shows higher vascular density and faster bone regeneration. Mechanistically, rGO activates FAK-Src/RELA, upregulates P4HA1, boosts collagen I synthesis, and drives ECM remodeling to create a pro-angiogenic niche. The targeting direction is clear: rather than only delivering growth factors, the material guides cells to remodel their own matrix.

Materials
rGO is green-synthesized from GO using R. rosea extract, retaining polyphenolic groups. It is mixed with Matrigel to form rGO@hydrogel at 5 μg/mL. The scaffold has an interconnected porous network with a mean pore size of ~72.73 μm, supporting nutrient diffusion and cell migration. About 50% mass remains at day 14, with complete degradation by day 28. rGO first contacts the cell membrane, triggers F-actin reorganization, and acts through FAK-Src/RELA/P4HA1 to promote collagen I deposition. The targeting focus is ECM remodeling coupled with prevascularization.

Disclaimer: This is only a frontier research update, not any related advice.#rGOHydrogel #Prevascularization #BoneRegeneration #SHED #ECMRemodeling #Biomaterials #Angiogenesis #ResearchFrontier
DOI: 10.1002/advs.75524