Therapeutic Biomaterials for Chronic Osteomyelitis: Time-Space-Control Strategies for Infection Control and Bone...

Chronic osteomyelitis and infected bone defects are driven by recurrent infection, biofilm persistence, and dysregulated inflammation, but conventional "eradicate bacteria and fill the defect" approaches often fail to restore a regenerative microenvironment. Herein, we review biofilm-associated immune dysfunction in impaired angiogenesis/osteogenesis and summarize biomaterials that couple infection control with tissue regeneration. We integrate representative platforms into a "Time-Space-Control" framework: (i) time-programmed systems that sequence early antibiofilm/antibacterial actions with later pro-angiogenic and osteogenic cues; (ii) space-focused designs that enhance defect localization, penetration, and coverage of infected niches; and (iii) controllable strategies that enable pathology-responsive and/or externally triggered, on-demand modulation. Based on this synthesis, we propose a practical 4P principle to guide programmable therapeutic biomaterials. Overall, explicitly managing timing, localization, and controllability may improve the alignment of antimicrobial therapy, immune reprogramming, and regenerative support for chronic infected bone repair.