Copper-Macrophage Crosstalk: Potential Molecular Mechanisms and Therapeutic Applications in Infected Wound Healing

Macrophages are highly abundant in skin tissues and play a central role in the wound healing process. However, persistent bacterial infections disrupt the wound microenvironment, leading to an imbalance in macrophage polarization. Copper ions have broad-spectrum antimicrobial properties and are actively involved in the entire process of wound healing. With the rapid development of nanomedicine, copper-based materials have shown great potential in wound healing. However, most studies have focused on the direct therapeutic effects of copper-based materials, ignoring their potential molecular mechanisms in regulating the wound microenvironment and their relevance to macrophage polarization. Therefore, this review introduces the origin and phenotypic diversity of macrophages in wounds, sequentially describes the key roles of macrophages and copper ions in wound repair, analyzes the interaction patterns and intrinsic mechanisms between copper ions and macrophages, and comprehensively summarizes the practical application of copper-based materials to promote wound healing by regulating the behavior of macrophages. In conclusion, elucidation of copper ion‒macrophage interactions will facilitate the development of copper-based materials for wound repair.