An immunomodulatory decellularized pulp matrix hydrogel promotes vascularized dental pulp regeneration through...

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.