Development and Characterization of Collagen Composites With Chemically Functionalized Mesoporous Silica Particles for Bone Tissue Engineering Applications

Mesoporous silica particles (MSPs) are widely investigated in biomaterials due to their high surface area, tunable porosity, and potential for chemical functionalization. In this study, MSPs were modified with different anionic functional groups (carboxyl, phosphate, and sulfonate) and incorporated into Type I collagen hydrogels to evaluate their structural, biological, and drug-loading behavior in the context of bone tissue engineering. A comprehensive set of analyses including FTIR, SEM/EDS, zeta potential, porosity, drug incorporation, cytocompatibility, in vitro mineralization, and short-term in vivo response was conducted. While calcium phosphate deposition was not observed in functionalized composites, the study reveals key insights into how the surface chemistry of MSPs modulates particle-collagen interactions, drug loading efficiency, and biological responses. Phosphate-modified MSPs showed higher cytotoxicity and interfered with collagen self-assembly, whereas MSPs bearing hydroxyl or carboxyl groups maintained better cytocompatibility and distribution within the matrix. Interestingly, MSPs functionalized with sulfonate groups exhibited enhanced simvastatin loading, likely due to their reduced surface polarity resulting from the formation of siloxane bridges in the oxidation process. In vivo implantation of unloaded composites in a rat tibial defect model confirmed good biocompatibility without evidence of acute inflammation. However, no significant bone formation or biomineralization was detected after 14 days. These findings suggest that excessive negative surface charge may impair ion-mediated mineralization and that the interplay between MSP chemistry and the biological environment must be carefully balanced. This work contributes to understanding the structure-function relationships in hybrid silica-collagen systems and identifies key parameters to optimize in future designs of osteoinductive and drug-eluting scaffolds.