Strategies to Microengineer Vascularized, Mineralized, and Immunomodulatory Niches for Dental Regeneration.

Abstract

Introduction: Regenerative endodontic therapies aim to restore the vitality and function of the dentin-pulp complex, including the vascularized and innervated pulp and mineralized dentin. Although cell homing, stem cell transplantation, and scaffold-based approaches have shown promise in immature teeth, outcomes in previously infected, fully formed adult teeth remain inconsistent. These limitations highlight the need to better understand the interactions among vascular, immune, and microbiological factors within the pulp microenvironment.

Methods: This narrative review examines the dentin-pulp complex from a microengineering perspective, synthesizing preclinical and clinical studies of strategies to engineer vascular, immune, and mineralized niches using bioactive and immune-informed materials.

Results: Current evidence indicates that regeneration depends on the coordinated restoration of interconnected vascular, immune, and mineralized niches. Prevascularized constructs may accelerate integration with the host vasculature and support pulp-like tissue formation, whereas scaffold composition, architecture, and mechanical properties regulate vascular stability and immune-cell behavior. However, residual bacterial products, particularly lipopolysaccharide, may sustain inflammation and compromise the regenerative signals provided by these materials. Dentin-derived matrix molecules and premineralized scaffolds can support mineralized tissue formation and provide an early protective barrier, but reinnervation, intracanal calcification, repair rather than true regeneration, and the limited availability of clinically scalable cell and matrix sources remain important challenges.

Conclusions: Predictable and functional regeneration of the dentin-pulp complex may require the integration of effective disinfection and lipopolysaccharide neutralization with immune modulation, prevascularized and premineralized scaffolds, and scalable sources of stem cells and dentin matrix. Strategies to restore functional innervation remain an important future direction.