Interfacial Protein Layer Formation on 45S5 and 59S Bioactive Glasses Enhances Cellular Compatibility and Angiogenic Activity

Bioactive glasses (BGs) undergo rapid surface modification upon exposure to physiological environments, where protein adsorption critically governs subsequent cellular and vascular responses. In this study, the interfacial and biological consequences of bovine serum albumin (BSA) adsorption on two silicate BG compositions, 45S5 and 59S, are systematically evaluated. Protein adsorption markedly alters the surface-mediated bioactivity of both glasses, with 59S BG exhibiting significantly greater protein affinity, consistent with its compositional characteristics and surface reactivity. Protein-conditioned BGs demonstrate enhanced cytocompatibility, supporting improved fibroblast adhesion, and proliferation, with the most pronounced cellular response observed for 59S BG/BSA. Ex vivo angiogenesis assays further reveal a substantial enhancement in vascular network formation following protein conditioning, following the trend: Control < 45S5 BG < 45S5 BG/BSA < 59S BG < 59S BG/BSA. These effects are attributed to the synergistic interaction between sustained therapeutic ion release and the establishment of a biologically active protein-modified interface. Collectively, the results show that protein adsorption fundamentally regulates BG-biological interactions and significantly enhances angiogenic and cell-supportive responses, positioning protein-conditioned 59S BG as a robust candidate for advanced tissue regeneration applications.