Carboxymethyl chitosan-stabilized Cu2O nanocomposites integrated into biomimetic 3D nanofibrous scaffolds for infected wound microenvironment modulation.

Infected wounds are difficult to treat due to multiple challenges, including bacterial invasion, oxidative stress, inflammation, and impaired angiogenesis. Copper-based nanomaterials, especially cuprous oxide (Cu2O), are promising candidates for infected wound therapy due to their redox-active Cu+/Cu2+ species and multifunctional biological activities. However, their biomedical translation is hindered by intrinsic instability, including rapid oxidation, aggregation, and uncontrolled ion release. Here, rather than using carboxymethyl chitosan (CMCS) merely as a passive coating or carrier, we exploit CMCS-derived coordination microenvironments to direct the in situ nucleation, growth, dispersion, and interfacial stabilization of Cu2O nanoparticles during particle formation. This strategy yields uniformly dispersed, oxidation-resistant Cu2O with sustained Cu+/Cu2+ release. CMCS further contributes intrinsic antioxidant and anti-inflammatory activities, complementing the antibacterial and angiogenic functions of Cu2O. The resulting CMCS@nano-Cu2O was incorporated into a biomimetic three-dimensional nanofibrous scaffold, coupling nanoscale coordination control with extracellular-matrix-like structural support within a single therapeutic construct. The integrated scaffold effectively inhibited bacterial growth, alleviated oxidative stress, promoted M2 macrophage polarization and angiogenesis, and markedly accelerated infected wound healing. This work establishes a chemical strategy for stabilizing redox sensitive Cu2O nanoparticles and presents a structurally and functionally synergistic 3D platform for effective microenvironmental regulation in infected wound repair.