Synchronizing degradation with regeneration: a model-driven framework for designing biodegradable biomaterials in...

Bone regeneration is a complex biological process, and the repair of critical-sized bone defects is often difficult, highlighting the need to develop biodegradable scaffolds that can effectively synergize with tissue repair. This paper introduces a model-based bone repair design framework that matches the kinetics of material degradation with the spatiotemporal stages of bone repair. We systematically evaluated the degradation mechanisms and tunability of four classes of biomaterials-metals (Mg, Fe, Zn), ceramics (HA, β-TCP, bioactive glass), polymers (PLGA, PCL), and composites-and mapped established mathematical models (linear partial differential equations, sigmoid curves, response-diffusion partial differential equations, and mechanobiological finite element models) to specific bone defect sizes and clinical scenarios. Based on this classification, we propose a four-step clinical design to guide researchers in completing the following steps: (1) calculating patient-specific healing timelines using first-order heuristics; (2) selecting appropriate material classes based on mechanical and biological requirements; (3) designing degradation kinetics to match the healing stages; and (4) validating scaffold-tissue alignment. To achieve quantitative assessment, we introduce the synchronization index (SI), a provisional index designed to quantify the correlation between actual implant degradation and patient-specific target curves. While the SI and the healing timeline formula are currently proposed only as conceptual design tools and require prospective experimental and clinical validation, their integration provides a structured path for scaffold development, moving it from experimental trial and error to precise, model-based engineering design. The goal of this framework is to facilitate the rational design of smart, resorbable implants that dynamically match the biological and mechanical requirements of bone regeneration.