Systemic vitamin D3 modulates mineralization and resorption dynamics of beta-tricalcium phosphate scaffolds in vivo

Calcium phosphate–based scaffolds such as beta-tricalcium phosphate (beta-TCP) are widely investigated for applications involving mineralized tissue environments; however, scaffold mineralization behavior and resorption kinetics are strongly influenced by host systemic factors. Vitamin D3 is a key regulator of calcium and phosphate metabolism and may modulate scaffold-mediated mineral deposition and remodeling. This in vivo study evaluated the effects of systemic and local vitamin D3 administration on the mineralization and resorption dynamics of beta-TCP scaffolds. Forty-eight female Wistar rats were randomly assigned to four groups: (1) collagen membrane control, (2) beta-TCP scaffold alone, (3) beta-TCP with local vitamin D3 administration (1800 IU delivered at the scaffold site), and (4) beta-TCP with systemic vitamin D3 administration (600 IU administered intraperitoneally once weekly for three weeks). Standardized 5-mm calvarial defects were created and treated according to group allocation. Animals were euthanized at 6 and 12 weeks. Scaffold mineralization and resorption were assessed using micro-computed tomography (micro-CT) and histomorphometric analyses, including quantification of newly mineralized tissue volume, mineral density, scaffold resorption, and mineralized area percentage. Statistical significance was defined as p<0.05. Systemic vitamin D3 administration resulted in significantly enhanced mineralization and altered resorption dynamics compared with local vitamin D3 delivery and control conditions. At 12 weeks, the systemic vitamin D3 group exhibited the highest newly mineralized tissue volume and mineralized area percentage, with values significantly greater than those observed in the beta-TCP-only and local vitamin D3 groups (p<0.001). Micro-CT analysis demonstrated increased mineral density (p<0.05) and accelerated beta-TCP resorption (p<0.01). Histological evaluation revealed more advanced mineralized tissue maturation and improved scaffold–tissue integration. Within the limitations of this study, systemic vitamin D3 administration significantly enhanced the mineralization and resorption dynamics of beta-TCP scaffolds in vivo . These findings highlight the influence of systemic mineral metabolism on scaffold performance and underscore the importance of considering host biochemical conditions when evaluating calcium phosphate–based biomaterials.