Influencing factors of pulp-dentin complex regeneration and related biological strategies

Regenerative endodontic therapy (RET) utilizing tissue engineering approach can promote the regeneration of pulp-dentin complex to restore pulp vascularization, neuralization, immune function and tubular dentin, therefore the regenerated pulp-dentin complex will have normal function. Multiple factors may significantly affect the efficacy of RET, including stem cells, biosignaling molecules and biomaterial scaffolds. Stem cells derived from dental tissues (such as dental pulp stem cells) exhibit certain advantages in RET. Combined application of multiple signaling molecules and activation of signal transduction pathways such as Wnt/β-catenin and BMP/Smad play pivotal roles in enhancing the potential of stem cell migration, proliferation, odontoblastic differentiation, and nerve and blood vessel regeneration. Biomaterials suitable for RET include naturally-derived materials and artificially synthetic materials. Artificially synthetic materials should imitate natural tissues for biomimetic modification in order to realize the temporal and spatial regulation of pulp-dentin complex regeneration. The realization of pulp-dentin complex regeneration depends on two strategies: stem cell transplantation and stem cell homing. Stem cell homing strategy does not require the isolation and culture of stem cells in vitro, so is better for clinical application. However, in order to achieve the true regeneration of pulp-dentin complex, problems related to improving the success rate of stem cell homing and promoting their proliferation and differentiation need to be solved. This article reviews the influencing factors of pulp-dentin complex regeneration and related biological strategies, and discusses the future research direction of RET, to provide reference for clinical translation and application of RET.