Modeling the structural and functional properties of bioactive glasses: Atomic to macro-scale perspectives

Bioactive glasses (BGs) have gained significant interest for medical applications, including bone defect reconstruction using glass powders, large-scale bone regeneration with scaffolds, and drug delivery via mesoporous glass nanoparticles. A key factor in these applications is the ability to control dissolution, which fundamentally depends on glass composition and atomic to micro- and macro-scale structures. While extensive experimental research has elucidated the relationship between composition, structure, apatite-forming ability, and dissolution behavior, computational modeling remains a powerful yet underexplored tool. BGs should be designed across multiple length scales to optimize ion release, porosity and mechanical properties. For example, bone's porous architecture enables nutrient transport, mechanical adaptability, and bioactivity-key features that computational approaches can help replicate in BGs. Through the application of multiscale modeling methodologies, encompassing atomic-level simulations such as molecular dynamics (MD), density functional theory (DFT), and topological constraint theory (TCT), meso-scale approaches like phase-field modeling, and macroscale techniques including finite element method (FEM), it becomes possible to systematically design BGs with enhanced performance. These computational tools facilitate the investigation of key parameters such as ion exchange/release mechanisms, network degradation behavior, and mechanical stability under physiological conditions. Consequently, a comprehensive modeling framework enables the development of BGs with controlled degradation rates, improved bioactivity, and optimized mechanical properties tailored to specific biomedical applications. STATEMENT OF SIGNIFICANCE: Bioactive glasses have revolutionized the fields of regenerative medicine and biomaterials due to their unique ability to bond with biological tissues and stimulate cellular responses. However, a comprehensive understanding of their structural and functional properties across multiple length scales, from atomic arrangements to macroscopic performance, remains a significant challenge. This work bridges that gap by reviewing modeling techniques to elucidate the atomic-scale structure, mesoscopic interactions, and macroscopic behavior of bioactive glasses. By integrating molecular dynamics simulations, mesoscale modeling, and continuum-level analyses, we provide critical insights into the relationships between composition, structure, and biological activity. The findings have broad implications for the rational design of next-generation bioactive glass materials tailored for biomedical and tissue engineering applications.