Beyond Reinforcement: Collagen-Inorganic Composites as a Roadmap for Next-Generation Biomaterials.

The convergence of materials science and biology has reshaped the design of biomaterials, exposing both new opportunities and unresolved challenges. Among natural polymers, collagen remains a cornerstone due to its biocompatibility and structural affinity with the extracellular matrix. However, its intrinsic mechanical weakness, rapid degradation, and limited bioactivity restrict its clinical potential. The incorporation of inorganic phasescarbon nanostructures, metallic nanoparticles, or functional oxideshas emerged as a route to overcome these limitations and introduce new functionalities such as antimicrobial protection, osteoconductivity, electrical responsiveness, and stimuli sensitivity. Yet, this hybridization introduces complex interfacial phenomena that demand careful architectural and chemical control. The spatial organization of pores, fibers, and surface topographies governs nutrient diffusion and cell alignment, while interface chemistry dictates stability, degradation, and biological signaling. Despite significant progress, reproducibility and long-term safety remain inconsistent across studies, hindered by variations in collagen source, particle distribution, and cross-linking strategies. Beyond empirical formulation, future progress requires mechanism-guided design frameworks that link composition, structure, and function to predictable biological outcomes. This review critically examines advances in collagen-inorganic composites, highlighting key structure-property-function relationships, manufacturing strategies, and translational barriers. By mapping trends through bibliometric analysis and synthesizing evidence from recent studies, it outlines a roadmap toward reproducible, multifunctional, and clinically relevant collagen-based biomaterials.