Strategies to microengineer vascularized, mineralized and immunomodulatory niches for dental regeneration.

Regenerative endodontic therapies aim to restore the biological vitality and function of dental pulp tissues, including the vascularized and innervated pulp and the mineralized dentin. While approaches such as cell homing, stem cell transplantation, and scaffold-based regeneration have shown promise in immature teeth, outcomes in previously infected mature, fully formed adult teeth remain inconsistent. These limitations highlight the need to better define the interactions among vascular, immune, and microbiological factors within the pulp microenvironment. This narrative review examines the dentin-pulp complex from a microengineering perspective, focusing on strategies to engineer vascular, immune, and mineralized niches using bioactive and immune-informed materials. It also outlines current challenges and future directions, emphasizing the integration of LPS neutralization, immune modulation, and fabrication of pre-vascularized and pre-calcified scaffolds with scalable stem cell and dentin matrix sources to enable predictable and functional regeneration of the dentin-pulp complex.