Self-supplying glucose/oxygen hydrogel enhances dental pulp stem cell survival and vascularized tissue regeneration through Erk1/2-VEGF signaling

Insufficient nutrient and oxygen supply remains a critical barrier to cell survival and tissue regeneration in three-dimensional scaffolds. Here, we developed a self-supplying glucose/oxygen hydrogel (SGO-Gel) that intrinsically provides sustained metabolic support for dental pulp stem cells (DPSCs). The hydrogel was constructed by crosslinking oxidized dextran with phenylboronic acid-grafted carboxymethyl chitosan through dynamic Schiff-base and phenylboronic ester bonds, yielding an injectable, self-healing network capable of releasing glucose upon dextranase degradation. Polydopamine-coated calcium peroxide nanoparticles were incorporated to achieve controlled oxygen release while maintaining structural stability. SGO-Gel exhibited a uniform porous architecture that facilitated nutrient diffusion, as confirmed by molecular dynamics simulations. In vitro , the hydrogel significantly enhanced DPSCs survival under combined glucose starvation and hypoxia, maintaining viability above 70 % after 7 days compared to less than 30 % in control gels. Transcriptomic analysis revealed activation of the MAPK/Erk1/2 pathway and upregulation of VEGF, which was consistent with functional assays showing enhanced endothelial migration and tube formation. In an ectopic transplantation model, SGO-Gel promoted the formation of vascularized pulp-like tissue with abundant collagen deposition and odontoblast differentiation. Overall, SGO-Gel shifts the paradigm from passive scaffolds to metabolically active matrices, offering a promising strategy for dental pulp regeneration and broader tissue engineering applications where ischemia and limited vascularization remain key challenges.