Scaffold-based Regenerative Endodontics: A Scoping Review of Orthotopic Regeneration Outcomes

Regenerative endodontic therapy (RET) has emerged as a biologically driven approach for managing immature teeth with necrotic pulps. Scaffolds are central to this process, providing structural support for the cells and delivering bioactive cues essential for pulp-dentine regeneration. This scoping review critically evaluates scaffold-based RET approaches assessed in orthotopic animal models, identifies key translational challenges and outlines future research directions. A literature search was conducted in PubMed, Scopus and Web of Science for studies published up to January 2025. Eligible studies included scaffold-based strategies tested in orthotopic models with histological assessment. The results were categorised by scaffold materials: (1) Natural polymers, (2) synthetic polymers, (3) platelet concentrates and (4) acellular extracellular matrices (ECMs). Twenty-seven studies met the inclusion criteria. Natural polymers, particularly collagen composite materials, tended to favour mineralised tissue over organised pulp-like regeneration. Scaffolds composed of gelatin seem a promising candidate, particularly when combined with dental pulp stem cells. Conflicting results have been reported regarding polysaccharide-based scaffolds, with chitosan showing promising potential, especially when combined with photobiomodulation therapy, although further research is needed. Platelet concentrates, including platelet-rich fibrin, facilitated apical closure but lacked consistent pulp-like tissue formation. Acellular ECMs, especially decellularised pulp matrices, demonstrated the most promising outcomes, promoting organised pulp-like tissue formation, although some inflammatory responses were noted. In summary, scaffold-based RET holds significant promise for pulp-dentine regeneration and root maturation. However, inconsistent outcomes remain a key limitation. Future research should focus on optimising scaffold design, standardising evaluation protocols and employing clinically relevant models to enhance clinical translation.