Chitosan-Based Nanoparticles and Biomaterials for Pulp Capping and Regeneration: A Systematic Review with Quantitative and Evidence-Mapping Synthesis

Preserving dental pulp vitality is a key goal in minimally invasive dentistry. Conventional materials such as calcium hydroxide and mineral trioxide aggregate (MTA) are effective but limited in bioactivity and mechanical strength. This systematic review evaluated the biological efficacy of chitosan-based nanoparticles and biomaterials for pulp capping and regeneration. Following PRISMA 2020 guidelines, electronic searches were conducted across five databases up to April 2025. Controlled in vitro and animal studies using chitosan-based nanoparticles, hydrogels, or composite scaffolds were included. Risk of bias was assessed using SYRCLE (animal) and ToxRTool (in vitro), and certainty of evidence was rated via the GRADE-Preclinical framework. Due to methodological heterogeneity, data were synthesized using direction-of-effect coding and visualized through Albatross and heatmap plots. Sixteen studies met the criteria, consistently demonstrating enhanced cell viability, mineralization, and upregulation of odontogenic and angiogenic markers (BMP-2, TGF-β₁, VEGF, DSPP) compared with MTA or calcium hydroxide. Animal models confirmed improved angiogenesis, reparative dentin formation, and pulp vitality preservation. Despite uniformly positive biological outcomes, the overall certainty was rated Low to Very Low owing to small samples and unclear randomization. Chitosan-based biomaterials show promising regenerative potential, warranting well-designed preclinical and clinical studies for translational validation.