Metal-Polyphenol Network-Based Biomaterials for Infected Bone Defects: Microenvironment Regulation and Stage-Oriented Regenerative Strategies.

Abstract

Infected bone defects are not simply bone defects complicated by bacterial infection; they are dynamic pathological niches in which biofilms, intracellular bacterial persistence, oxidative stress, dysregulated immunity, vascular failure, and pathological bone remodeling are mutually reinforcing. This coupling explains why bacterial killing alone rarely restores functional bone. Metal-polyphenol networks (MPNs), assembled through reversible coordination between metal ions and polyphenols, can translate these pathological stimuli into programmable therapy. Their tunable composition, interfacial adhesion, and pH/redox-responsive disassembly support a therapeutic transition from early infection control to redox-inflammatory regulation and vascularized bone regeneration. This review presents a disease-oriented framework connecting MPN chemistry and architecture with the evolving microenvironment of infected bone defects. Recent strategies for targeting planktonic and biofilm-associated bacteria, balancing reactive oxygen species generation and scavenging, reshaping osteoimmune signaling, protecting mitochondrial function, coupling angiogenesis with osteogenesis, and rebalancing bone remodeling are critically examined. Emphasis is placed on stage-oriented design, therapeutic trade-offs, and translational gaps. Priorities include eliminating hidden bacterial reservoirs, controlling ion dosing and long-term safety, evaluating functional vascularization and mechanical integration, and standardizing disease models. MPNs are thereby positioned as programmable platforms that coordinate infection resolution with durable bone regeneration.