Extracellular Matrix-Based and Extracellular Matrix-Bioinspired Scaffolds for Extracellular Vesicle Delivery in Dental Pulp Regeneration: A Narrative Review.

Abstract

Vital pulp therapy aims to preserve pulp vitality by stimulating reparative processes. However, conventional approaches often result in incomplete tissue regeneration. Extracellular vesicles (EVs) have emerged as promising cell-free therapeutic agents because of their ability to regulate angiogenesis, odontogenesis, and immune responses through the transfer of bioactive molecules. Despite their significant regenerative potential, the clinical application of EVs remains limited by rapid clearance, insufficient local retention, and uncontrolled release following administration. To address these challenges, various extracellular matrix (ECM)-based and ECM-bioinspired scaffolds have been developed as delivery platforms. These scaffolds can provide structural support and enable controlled, localized release of EVs. This narrative review critically evaluates the current evidence regarding scaffold systems as EV delivery platforms for dental pulp regeneration, comparing their biological performance, methodological quality, and translational potential. Across the available studies, scaffold-assisted EV delivery consistently enhanced angiogenesis, odontogenic differentiation, mineralization, and immunomodulation; however, the evidence remains preclinical and is characterized by substantial heterogeneity regarding EV source, isolation and characterization methods, scaffold composition, experimental models, and outcome assessment. Current findings support the feasibility of scaffold-assisted EV delivery for regenerative endodontics, but important challenges remain, including standardization of EV production and characterization, scalable manufacturing, regulatory approval, and demonstration of long-term safety and functional pulp-dentin complex regeneration. Further well-designed translational and clinical studies will be essential before routine clinical implementation can be considered.