Evaluation of stem cell-derived extracellular vesicles versus platelet-rich fibrin in regenerative endodontics

Abstract

Regenerative endodontics has emerged as a biologically driven approach for preserving natural teeth by restoring
the vitality and function of the pulp–dentin complex. Among the most promising regenerative strategies
are stem cell-derived extracellular vesicles (EVs) and platelet-rich fibrin (PRF), both of which provide bioactive
molecules that promote tissue repair and regeneration through distinct mechanisms. Stem cell-derived EVs
represent a cell-free therapeutic modality capable of enhancing intercellular communication, angiogenesis,
immunomodulation, neurogenesis, and odontogenic differentiation while minimizing concerns associated with
direct stem cell transplantation. PRF, an autologous platelet concentrate, serves as a natural scaffold that gradually
releases growth factors to support wound healing, stem cell recruitment, vascularization, and periapical
tissue regeneration. This review evaluates the biological characteristics, mechanisms of action, regenerative
potential, clinical applications, advantages, and limitations of stem cell-derived EVs and PRF in regenerative
endodontics. It also highlights current evidence regarding their comparative therapeutic performance, discusses
challenges related to clinical translation, and explores future directions, including biomaterial integration
and artificial intelligence-assisted treatment evaluation. Both approaches demonstrate considerable promise
for improving regenerative outcomes, although further standardized clinical studies are required to establish
optimal therapeutic protocols and long-term clinical efficacy.