Decellularized dental pulp extracellular matrix for pulp-dentin regeneration: a narrative review of processing, bioactivity, delivery, preclinical evidence, and translational challenges

Abstract

Regenerative endodontics is intended to bring living function back to the pulp-dentin complex. That means restoring blood supply, neural support, immune activity, and dentin formation, not simply filling the canal with repair tissue. Blood-clot-based procedures can promote healing, but the tissue that forms is often uneven and does not closely resemble normal pulp. This limitation has drawn attention to decellularized dental pulp extracellular matrix (DPECM). DPECM keeps part of the native three-dimensional framework together with collagens, glycosaminoglycans, matricellular proteins, and matrix-bound signals. The objective of this narrative review is to critically evaluate how native dental pulp-derived DPECM is prepared and delivered, what biological effects and candidate mechanisms are directly supported, and what evidence gaps limit clinical translation. A focused PubMed search from database inception to 31 July 2026 used terms for dental pulp, decellularized extracellular matrix, DPECM, and regenerative endodontics; reference-list screening supplemented the search, and 101 articles were retained for narrative synthesis. Across the available, predominantly preclinical literature, DPECM has generally been associated with dental pulp stem-cell adhesion and migration, several differentiation programs, and angiogenic, neural-marker, and immune-remodeling outcomes. Whole-pulp scaffolds preserve tissue architecture more faithfully. Solubilized hydrogels, microgels, and photocrosslinked composites are easier to place in irregular root canals, although some structural information is lost during processing. Comparative omics has started to explain why pulp-derived matrix may behave differently from other matrices. Candidate tenascin-C/Notch signaling is one example. Another recurring theme is the coupling of macrophage behavior with vascular and odontogenic repair. Recent orthotopic canine studies provide stronger preclinical evidence of pulp-like tissue with dentinogenic, vascular-marker, and neural-marker outcomes, but not restored function. Even so, most evidence still comes from cell culture, ectopic implantation, or short animal experiments. Differences in tissue source, processing, controls, and outcome definitions make effect sizes difficult to compare. The next stage of the field will require agreed quality attributes, practical potency assays, infected-root models, long-term functional outcomes, and direct comparison with current regenerative procedures. DPECM remains a predominantly preclinical strategy: no direct human clinical evaluation of a DPECM-based therapeutic product was identified, and translation will require reproducible manufacturing, disease-relevant testing, and durable functional outcomes.