Bioactive molecule delivery platforms in regenerative endodontic therapy: A systematic review and meta-analysis

This systematic review examines emerging delivery systems for bioactive molecules within regenerative endodontic therapy (RET) where hydrogels, nanogels, and polymeric nanoparticles along with advanced nanocarriers such as liposomes aquasomes, vesosomes, and mesoporous silica nanoparticles form the primary focus. The extensive literature search in PubMed, Scopus, and Web of Science databases (until August 2025) yielded a total of 47 eligible articles, including in vitro, ex vivo, animal, and a few clinical studies. Hydrogels emerged as a significant category, showcasing enhanced regenerative effects when used for the sustained release of various growth factors such as transforming growth factor-beta (TGF-β₁), bone morphogenetic protein-2 (BMP-2), and vascular endothelial growth factor (VEGF). This was associated with improved angiogenesis and odontogenic differentiation. Nanogels exhibited high protein-loading efficiency and facilitated the differentiation of dental pulp stem cells, while polymeric nanoparticles demonstrated prolonged antibiotic and growth factor delivery with lower cytotoxicity. Among advanced nanocarriers, mesoporous silica nanoparticles showed promising potential for controlled release of growth factors and the formation of pulp-like tissues in animal models. In summary, the selected platforms for the delivery of bioactive molecules within RET show significant promise in terms of enhancing cell viability, bioactivity, and tissue regeneration. The findings indicate a practical pathway for clinicians aiming to achieve successful pulp-dentin tissue regeneration through translation research.