Dentistry has made enormous strides in the last century, particularly at better understanding the challenges and opportunities in endodontics pertaining to engineering a metabolically active and functional (blood carrying) dental pulp capable of forming new dentin. Of note, based on the rather unpredictable levels of success with current treatment modality (evoked bleeding), the last decade has witnessed major developments toward the generation of innovative multifunctional (e.g., antimicrobial, immunomodulating, regenerative) biomaterials therapeutics to devise cell-friendly disinfection and predictable pulp and dentin regeneration strategies. In this symposium, we anticipate to gather clinicians and researchers from around the globe, focusing on the emerging field of regenerative endodontics to promote discussion, interaction, and cross-discipline networking to underscore new discoveries and potential therapeutic platforms to advance clinical translation. In terms of novel biomaterials, latest developments in the synthesis of injectable and on-demand, that is matrix metalloproteinases-sensitive hydrogels for infection ablation and hard tissue regeneration will be discussed. Meanwhile, an innovative nitric oxide releasing biomimetic nanomatrix gel with proven disinfection and pulp-dentin tissue regeneration capacities will be highlighted. Furthermore, considering that wound repair involves a complex interplay between connective tissue matrix and host/immune cells under the influence of cytokines/mediators in a low bacterial load environment, this symposium will also discuss the ability of nanoparticles guided microtissue engineered dentin to inactive bacterial biofilm and modulate host/immune cells for tissue regeneration. Lastly, organoids, hDPSC derived extracellular vesicles, apical papilla constructs and biomaterials as tools for dental tissue regeneration, will also be addressed.