PURPOSE: To investigate the efficacy of chitosan and calcium carbonate (CaCO₃)-based scaffolds in promoting bone regeneration in preclinical in vivo models, focusing on bone volume, mineral density, histological outcomes, and biomechanical properties. METHODS: This systematic review adheres to PRISMA guidelines. A comprehensive search was conducted across PubMed, Web of Science, Scopus, and Cochrane Library for studies published from March 2015 to March 2025 using keywords such as "chitosan," "calcium carbonate," "bone regeneration," and "scaffolds." Eligible studies involved preclinical in vivo research on bone defect repair with chitosan or calcium carbonate scaffolds. Studies were included if they compared these scaffolds with other bone regeneration materials or no intervention. The methodological quality of the studies was assessed using the SYRCLE Risk of Bias tool. RESULTS: Thirty preclinical in vivo studies involving 850 animals were included. Chitosan scaffolds showed new bone formation ranging from 40% to 85%, while calcium carbonate scaffolds showed regeneration rates between 50% and 70%. Significant improvements in bone mineral density (BMD), bone volume-to-total volume ratio (BV/TV), and trabecular thickness were observed in scaffold-treated groups. Histological findings indicated increased osteoblast activity, mineralization, and vascularization, especially in chitosan combined with other materials. No significant biomechanical differences were found between the scaffolds, but composite materials showed improved mechanical properties (p < 0.05). CONCLUSIONS: Both chitosan and calcium carbonate-based scaffolds show promising potential in preclinical models, with chitosan reporting 40-85% new bone formation (≈19 studies) and CaCO₃ reporting 50-70% (≈11 studies). However, heterogeneity in study design and reporting quality warrants cautious interpretation. This variability also underscores the need for standardized testing and further research to isolate the independent effects of scaffold composition.
Marampa et al. (Mon,) studied this question.