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Imbalance of metal ions in the wound microenvironment is a key factor that leads to delayed wound healing. However, single metal administration to enhance wound repair is usually not enough due to the overlapping nature of the wound healing phases. Herein, a facile freeze‐thawing strategy is developed to incorporate chitosan/ions hydrogel into medical gauzes to realize on‐demand release of multiple ions to accelerate wound healing. In vitro study reveals that the gauzes can temporally release multiple metal ions on demand, and the released metal ions show effectiveness in killing bacteria and expediting cell migration. In vivo studies demonstrate that the metal ions loaded gauzes can efficiently enhance infected wound healing. Further histological analysis find that these metal ion‐loaded gauzes accelerate wound healing by promoting granulation formation, collagen deposition and maturation, re‐epithelization, angiogenesis, and inhibiting inflammation via regulating the expression of inflammatory factors (e.g., tumor necrosis factor‐α) and polarization of macrophages. Thus, this novel metal ions delivery system has great potential in infected tissue repair and antibacterial applications. Chitosan/metal ions hydrogels are coated to medical gauzes through a simple freeze‐thawing strategy to realize on‐demand release of multiple metal ions for improved wound healing by promoting granulation formation, collagen deposition and maturation, re‐epithelization, angiogenesis, and inhibiting inflammation via regulating the expression of inflammatory factors (e.g., tumor necrosis factor‐α) and polarization of macrophages.

Efficient reconstruction of a fully functional skin after wounds requires multiple functionalities of wound dressing due to the complexity of healing. In these regards, topical administration of functionalized nanoparticles capable of sustainably releasing bioactive agents to the wound site may significantly accelerate wound repair. Among the various nanoparticles, superparamagnetic iron oxide (Fe3O4) nanoparticles gain increasing attractiveness due to their intrinsic response to an external magnetic field (eMF). Herein, based on the Fe3O4nanoparticle, we developed a fibroblast growth factor (bFGF)-loaded Fe3O4nanoparticle using a simple mussel-inspired surface immobilization method. This nanoparticle, named as bFGF-HDC@Fe3O4, could stabilize bFGF in various conditions and exhibited sustained release of bFGF. In addition, an in vitrostudy discovered that bFGF-HDC@Fe3O4could promote macrophage polarization toward an anti-inflammatory (pro-healing) M2 phenotype especially under eMF. Further, in vivofull-thickness wound animal models demonstrated that bFGF-HDC@Fe3O4could significantly accelerate wound healing through M2 macrophage polarization and increased cell proliferation. Therefore, this approach of realizing sustained the release of the growth factor with magnetically macrophage regulating behavior through modification of Fe3O4nanoparticles offers promising potential to tissue-regenerative applications.