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.