DESIGNING MULTICOMPONENT BORATE GLASSES: AN INTEGRATED COMPOSITION-STRUCTURE-PROPERTY-FUNCTION FRAMEWORK

Abstract

The rational design of biomaterials capable of orchestrating coordinated therapeutic responses remains an unresolved challenge in biomedical research. In bioactive glass development, discovery has largely relied on empirically driven strategies that vary components in isolation, limiting predictive understanding of interaction-governed behavior in multicomponent systems. This limitation is particularly pronounced in dental caries management, where brief clinical exposures necessitate rapid, synergistic ion delivery for simultaneous remineralization and antibacterial efficacy within stringent safety parameters. Addressing this, the present thesis establishes a safety-constrained, composition-driven framework for the translational design of multicomponent borate bioactive glasses tailored for cariostatic and antimicrobial applications. Employing a five-component system (B2O3-CaO-Ag2O-NaF-Na2SO4), a Design of Mixtures (DoM) methodology was applied within a bounded compositional simplex to systematically interrogate sixteen engineered formulations. Interaction-resolved mapping of composition-structure-property-function relationships integrated Raman and 11B MAS-NMR spectroscopy with thermal, physical, dissolution, multi-ion release, and antibacterial evaluations. Coexisting modifiers induced non-additive reorganization of the borate network topology, governing early dissolution kinetics, ion availability, and bactericidal activity. Calcium modulated long-term mass loss and served as a compositional proxy for mineralization permissiveness via Ca2+ availability. Silver dictated early reactivity and elicited concentration-dependent antibacterial inhibition under clinically relevant exposure conditions. Fluoride facilitated network depolymerization and enhanced the availability of ions relevant to mineralization, without directly controlling the dissolution kinetics. Notably, interaction effects between modifiers often exceeded the magnitude of individual component effects, underscoring that network reconfiguration and functional outcomes are governed by coupled compositional balances. These insights reveal that multicomponent borate glass behavior cannot be extrapolated reliably from binary analogs and is more appropriately resolved within a statistically robust and systematically navigable mixture design space. Dissolution testing aligned with clinically representative exposure durations was implemented within an ISO 10993-17-compliant toxicological risk assessment, embedding regulatory thresholds as explicit early-stage design constraints rather than retrospective validation criteria. By synergizing antibacterial efficacy with conservative margin-of-safety analyses, a therapeutic window within the compositional simplex was identified. Collectively, this work advances borate bioactive glasses from empirical formulations toward predictive, safety-aware systems engineering, establishing a composition-structure-property-function paradigm that enables translational biomaterials design from conceptualization to clinical application.