Enamel Matrix Derivative in Dental Pulp Regeneration: Biological Basis, Mechanistic Insights, and Translational...

Enamel matrix derivative (EMD) has attracted increasing attention in regenerative endodontics because of its potential to influence multiple biological processes involved in dental pulp healing. Derived from enamel matrix proteins (EMPs), EMD has been associated with the regulation of stem/progenitor cell migration, odontogenic differentiation, angiogenic activity, and inflammatory responses. This review summarizes current evidence regarding the role of EMD in dental pulp regeneration, with emphasis on its biological characteristics, underlying mechanisms, and integration with biomaterial systems. Available studies suggest that EMD may contribute to a regeneration-permissive microenvironment by modulating cellular behavior and extracellular matrix-related processes, while biomaterial-based delivery strategies have been explored to improve its stability and local bioactivity. However, most existing evidence is derived from in vitro studies or nonpulp regenerative models, and direct evidence supporting functional pulp regeneration remains limited. In addition, EMD, Emdogain, recombinant amelogenin (Am), and Am-derived peptides are closely related but should not be considered interchangeable interventions. Taken together, EMD represents a biologically relevant but not yet fully validated approach in regenerative endodontics, and further studies are required to clarify its mechanisms under clinically relevant conditions and to distinguish true pulp regeneration from partial reparative outcomes.