Exosome-Based Therapeutics in Regenerative Dentistry: A Critical Review of Current Evidence and Translational Perspectives

Abstract

Abstract

Regenerative dentistry has evolved considerably over the past decade with increasing emphasis on biologically driven therapeutic approaches capable of restoring the structural and functional integrity of oral tissues. Among the emerging regenerative strategies, exosome-based therapy has attracted substantial scientific interest because of its ability to mediate tissue repair through cell-free mechanisms. Exosomes are nanosized extracellular vesicles secreted by multiple cell types, particularly mesenchymal stem cells, and contain biologically active molecules including proteins, lipids, messenger RNA, microRNA, cytokines, and growth factors involved in intercellular signaling and tissue remodeling.

Recent evidence suggests that exosomes possess substantial regenerative potential in regenerative endodontics, periodontal regeneration, bone tissue engineering, implantology, oral wound healing, oral oncology, and temporomandibular joint repair. Their therapeutic effects are largely attributed to anti-inflammatory, angiogenic, osteogenic, and immunomodulatory properties capable of enhancing cellular proliferation, differentiation, extracellular matrix synthesis, and tissue remodeling. Compared with conventional stem-cell transplantation, exosome-based therapeutics demonstrate several advantages including lower immunogenicity, minimal tumorigenic risk, improved biosafety profile, easier storage, and fewer ethical concerns.

Despite promising preclinical findings, several barriers continue to limit routine clinical implementation, including lack of standardized isolation protocols, heterogeneity in exosome composition, difficulties in large-scale manufacturing, limited long-term clinical evidence, and unresolved regulatory concerns. This review critically synthesizes current evidence regarding the biological mechanisms, regenerative applications, translational challenges, and future perspectives associated with exosome-based therapeutics in regenerative dentistry.