Application of Dental Stem Cell-Derived Extracellular Vesicles in Oral Tissue Engineering

Oral diseases, including dental caries, periodontitis, and bone defects, are highly prevalent globally and significantly impair patients' quality of life. Conventional clinical treatments, such as root canal therapy, basic periodontal therapy, guided bone regeneration, and bone grafting surgery, can partially control infections or repair tissue defects, but achieving complete functional regeneration remains challenging. Recent advancements in regenerative medicine and tissue engineering have provided novel therapeutic strategies for oral diseases. Among these strategies, dental stem cells have garnered significant attention due to their ease of isolation, multilineage differentiation potential, and immunomodulatory properties. Nevertheless, direct stem cell transplantation is still hindered by challenges such as immune rejection, tumorigenicity, and low cell survival rates, etc. Stem cell-derived extracellular vesicles (EVs), as an emerging cell-free therapeutic modality, can effectively recapitulate the therapeutic effects of their parental stem cells while effectively circumventing the risks associated with live-cell transplantation, thus becoming a prominent research focus in oral tissue engineering. The present paper conducts a narrative review of the classification and characteristics of dental stem cells (DSCs), as well as the fundamental concepts, classification, and biological functions of extracellular vesicles. Furthermore, it specifically highlights the applications of DSC-derived extracellular vesicles (DSC-EVs) in oral tissue engineering, including bone regeneration, pulp-dentin complex regeneration, periodontal tissue regeneration, and nerve regeneration. In addition, this review thoroughly examines critical challenges related to the isolation and purification, standardized production, elucidation of mechanisms of action, and clinical translation of DSC-EVs, while proposing future research directions and development prospects. The ultimate goal is to offer theoretical foundations and innovative insights to facilitate the clinical application of DSC-EVs in oral regenerative medicine.