A LECT2-eluting in situ coaxial electrospun nanofiber dressing orchestrates oxidative stress resolution and immune reprogramming for accelerated wound healing

Background: The development of multifunctional dressings capable of actively orchestrating the complex wound microenvironment remains a critical challenge in regenerative medicine. Although leucocyte cell-derived chemotaxin-2 (LECT2) has been implicated in inflammation and angiogenesis, its therapeutic potential in wound healing remains unexplored. Results: Here, we report a novel, portable coaxial electrospinning system for the in situ fabrication of a bioactive nanofiber dressing that continuously delivers functional LECT2. This dressing features a unique polyvinyl butyral (PVB)/polyvinylpyrrolidone (PVP) core and a polyvinyl alcohol (PVA)/PVP shell, which together ensure sustained LECT2 release. We demonstrate that LECT2 acts as a potent multi-target agent: it directly scavenges reactive oxygen species by upregulating the NRF2/SOD axis in keratinocytes and fibroblasts, promotes angiogenesis under oxidative stress, and exerts antimicrobial activity against S. aureus and Methicillin-resistant Staphylococcus aureus. Crucially, LECT2 drives immune reprogramming by polarizing macrophages toward a pro-regenerative M2 phenotype. The resulting dressing exhibits excellent mechanical properties and air permeability, and facilitates rapid wound closure in vivo by simultaneously enhancing re-epithelialization, neovascularization, and M2 macrophage polarization. Conclusions: This work not only unveils LECT2 as a master regulator of wound healing but also establishes a versatile platform for in situ fabrication of advanced dressings, with great promise for the treatment of complex skin wounds.