An oxygen-glucose co-releasing platform fostering dental pulp regeneration by driving metabolic recovery of stem cells.

In dental pulp regeneration, the ischemic microenvironment within the root canal severely compromises the survival and function of transplanted human dental pulp stem cells (hDPSCs). Here, we developed a PDMS-based core-shell oxygen-glucose delivery platform (P-C@P-G) that continuously released oxygen and glucose for up to 40 and 29 days, respectively, while minimizing peroxide-associated cytotoxicity through diffusion-controlled regulation without the need for exogenous enzymes. Under oxygen-glucose deprivation (OGD, 0.1% O2, glucose-free conditions) conditions, P-C@P-G improved cellular metabolic activity and enhanced hDPSC survival, proliferation, migration, and odontogenic differentiation. Compared with single-substrate supplementation, dual oxygen-glucose delivery produced greater improvements in hDPSC survival and differentiation. Transcriptomic and molecular analyses revealed alterations in TNF-α/NF-κB and Wnt/β-catenin signaling pathways following treatment. In vivo, P-C@P-G promoted pulp-like tissue regeneration, vascularization, and dentin sialophosphoprotein (DSPP) expression, resulting in greater pulp-like tissue formation and vascularization than the control group. Collectively, these findings demonstrated that sustained oxygen-glucose delivery effectively alleviated ischemia-associated metabolic insufficiency and revealed distinct contributions of oxygen and glucose to dental pulp regeneration.