Next-generation polymeric nanoparticles for regenerative endodontics: engineering the pulp microenvironment beyond antimicrobial therapy.

Regenerative endodontics aims not only to control infection but also to restore a functional pulp-dentin complex. Achieving this predictably remains challenging because disinfection, inflammation, blood vessel formation, matrix remodeling, and stem cell behavior are closely connected. Polymeric nanoparticles are increasingly being explored as a way to influence this complex environment because they can deliver therapeutic agents in a controlled and, in some cases, responsive manner. This review examines how the pulp microenvironment affects regenerative outcomes and discusses nanoscale strategies that target key aspects of this process, including infection-driven inflammation, macrophage behavior, hypoxia and vascular dysfunction, matrix reconstruction, and odontogenic differentiation. Current evidence suggests that nanoparticle performance depends not only on the cargo itself, but also on how it is released, the material design, responsiveness to biological signals, and the timing of delivery. These factors can significantly influence the behavior of regenerative cells. However, most studies remain preclinical, and no single platform has yet been able to coordinate all of these functions throughout the entire process of pulp regeneration. Future approaches will likely need to move beyond simply combining several therapeutic agents in one particle and instead focus on systems that can respond to changes in the pulp microenvironment over time. Whether these systems can do so while maintaining cytocompatibility, reproducibility, manufacturability, and clinical practicality will be important for their future use in regenerative endodontics.