Translational Readiness of Dental Pulp Stem Cell and Extracellular-Vesicle Products: Manufacturing, Delivery, Safety, and Clinical Development.

Abstract

Dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHED), and extracellular vesicles (EVs) show regenerative potential, but clinical translation depends on a reproducible product-process-procedure system. This systematic scoping review mapped how DPSC- and EV-containing dental products are defined, manufactured, formulated, dosed, delivered, monitored, and regulated. Following Joanna Briggs Institute guidance (JBI) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR), an umbrella-assisted strategy combined two recent high-coverage reviews with a targeted update through July 15, 2026. Data were charted for source, characterization, carrier, dose, delivery, visualization, safety, outcomes, and manufacturing readiness; a nine-domain review-level framework (Translational Readiness Appraisal for Dental cell and EV products) summarized relative maturity without serving as a validated clinical score. The map comprised 52 unique primary reports and nine methodological or secondary sources. Scaffold-based DPSC/SHED studies generally favored cell-containing constructs, but most were heterogeneous short-term animal experiments. Small human studies of autologous DPSC or SHED products reported encouraging feasibility and few serious safety signals, yet were underpowered for effectiveness or uncommon harms. Dental EV evidence remained predominantly preclinical; isolation, particle-normalized dosing, potency, storage, biodistribution, and batch comparability were frequently incomplete. Magnification was not consistently standardized as a delivery variable. Relative readiness was highest for autologous DPSC pulp products, intermediate for DPSC-scaffold bone or periodontal products, and low for dental EV products. Translation now requires indication-specific potency assays, carrier-product codevelopment, dose-response and biodistribution studies, documented delivery fidelity, standardized outcomes, long-term safety follow-up, and explicit good manufacturing practice (GMP) and regulatory strategies before confirmatory trials.