ECM remodeling by PDGFRβ+ dental pulp stem cells drives angiogenesis and pulp regeneration via integrin signaling.

BACKGROUND: This study investigates the role of PDGFRβ+ dental pulp stem cells (DPSCs) in dental pulp vascular development by remodeling the extracellular matrix (ECM), with implications for angiogenesis and pulp regeneration using GelMA hydrogels. METHODS: PDGFRβ+ DPSCs were assessed for ECM remodeling and angiogenesis via secretion of ECM proteins (FN, LAMA4, COL1A2). Immunofluorescence and gene expression analyses were performed to evaluate ECM composition and related signaling pathways. GelMA hydrogels loaded with PDGFRβ+ DPSCs were tested for angiogenic support in vitro (HUVEC tube formation) and in vivo (subcutaneous implantation in mice for 6 weeks). RESULTS: PDGFRβ+ DPSCs enhanced ECM deposition and modulated angiogenic signaling, promoting vascular development. Encapsulation in GelMA hydrogels supported HUVEC tube formation and facilitated organized pulp-like tissue with increased ECM and angiogenesis in vivo. Integrin pathway inhibition diminished these effects, highlighting the importance of ECM-integrin signaling in angiogenesis. CONCLUSION: PDGFRβ+ DPSCs regulate dental pulp vascular development through ECM remodeling. Their encapsulation in GelMA hydrogels provides a promising strategy for pulp regeneration by establishing an ECM-mediated angiogenic environment, offering potential for clinical pulp-dentin complex repair.