Human Hair–Derived Carbon Dot–Functionalized Scaffolds for Metabolism‐Targeted Antibacterial Therapy and Regeneration of Infected Bone Defects

Vollständiger Abstract

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ABSTRACT Infected bone defects (IBDs) represent a major clinical challenge in which persistent infection, microenvironmental dysregulation, and impaired regeneration reinforce a vicious cycle that is difficult to resolve. Here, we report carbon dot–functionalized Haversian‐mimetic scaffolds designed to combine antibacterial activity with regenerative support in IBDs. A 3D‐printed scaffold fabricated by digital light processing is constructed by integrating human hair–derived carbon dots (CrCi‐CDs) into a silk fibroin methacrylate (SilMA)/gelatin methacrylate (GelMA) network, yielding the CrCi‐CDs/SilMA/GelMA scaffold (CSG). In this biomimetic scaffold, CrCi‐CDs provide metabolism‐targeted antibacterial activity. Combined transcriptomic and metabolomic analyses indicate that they damage bacterial membranes and interfere with central energy metabolism and key biosynthetic pathways. In parallel, CSG reprograms the inflammatory microenvironment by promoting macrophage polarization toward a pro‐healing M2 phenotype, while simultaneously enhancing vascular network formation and osteogenic differentiation of bone marrow mesenchymal stem cells. In a rat model of methicillin‐resistant Staphylococcus aureus (MRSA)‐infected femoral condyle defects, CSG exhibited coordinated antibacterial, immunomodulatory, and pro‐regenerative effects, resulting in enhanced bone repair. These findings support the potential of the carbon dot–functionalized Haversian‐mimetic scaffold as a promising strategy for infected bone defect repair.