An Immunomodulatory Decellularized Pulp Matrix Hydrogel Promotes Vascularized Dental Pulp Regeneration Through Angiogenic-Odontogenic Coupling

Maintaining the vitality of inflamed or exposed pulp is critical for long-term tooth preservation in clinical dentistry. Vital pulp therapy (VPT), achieved by placing bioactive materials over the exposed pulp tissue, aims to preserve pulp function and stimulate dentin–pulp healing. However, effective regeneration requires biomaterials capable of orchestrating early inflammatory resolution, immune modulation, and coordinated angiogenic–odontogenic responses. Here, we engineered an injectable porcine derived decellularized dental pulp matrix (pDPM) hydrogel with intrinsic immunomodulatory properties to promote vascularized dental pulp regeneration. The pDPM retained abundant pulp-specific extracellular matrix components and bioactive factors while displaying excellent biocompatibility. In vitro, solubilized pDPM stimulated PI3K/AKT pathway activation and promoted macrophage polarization toward the M2 phenotype. Using preconditioned Transwell co-culture models, pDPM was shown to facilitate angiogenic–odontogenic paracrine interactions, characterized by enhanced angiogenic activation of endothelial cells and promoted odontogenic differentiation of dental pulp stem cells. In a rat direct pulp capping model, pDPM hydrogel treatment resulted in robust dentin bridge formation accompanied by enhanced neovascularization and a pro-regenerative immune microenvironment. Taken together, our findings demonstrate that pDPM integrates immunomodulatory and angiogenic–odontogenic to support vascularized dental pulp regeneration, highlighting its potential as a next-generation biomaterial for clinical VPT.