Exosome-loaded injectable hydrogel for regeneration of the dentin-pulp complex: An in vivo study

Abstract

Regeneration of the dentin-pulp complex has emerged as a promising approach in modern regenerative endodontics, aiming to restore the structural integrity and biological function of damaged dental pulp rather than relying solely on conventional reparative procedures. Among the innovative biomaterial-based strategies, exosome-loaded injectable hydrogels have attracted considerable attention because they combine the regenerative potential of extracellular vesicles with the supportive properties of biocompatible hydrogel scaffolds. Exosomes contain a diverse range of bioactive molecules, including proteins, lipids, and nucleic acids, which regulate cellular communication, promote angiogenesis, stimulate odontogenic differentiation, and modulate inflammatory responses. Injectable hydrogels provide a three-dimensional microenvironment that enables localized delivery, sustained release of exosomes, and effective adaptation to irregular pulp chamber anatomy. In vivo investigations have demonstrated encouraging outcomes, including enhanced pulp tissue regeneration, increased vascularization, formation of reparative dentin, reduced inflammatory reactions, and improved tissue integration. These findings suggest that exosome-loaded injectable hydrogels represent a promising cell-free therapeutic strategy capable of overcoming many limitations associated with stem cell-based therapies. Despite these advances, challenges remain regarding the standardization of exosome isolation, optimization of hydrogel formulations, large-scale production, long-term biosafety, and clinical translation. Continued preclinical and clinical investigations are essential to establish their efficacy, safety, and potential for routine application in regenerative endodontic practice.