A Fibrous Dressing Integrating Advanced Nanomicro Hybrid Structure with Effective Drug Delivery for Accelerated Wound Healing

Constructing fibrous dressings integrating innovative physical cues with appropriate biological cues is crucial for enhancing wound healing and reducing patient's discomfort. In this study, a series of nanomicro conjugated fibrous dressings (NCFDs) were constructed via conjugated electrospinning, comprising poly(caprolactone) (PCL) microfibers (diameter >2 μm) with/without zinc oxide (ZnO) nanoparticles and PCL nanofibers (diameter <100 nm) with/without resveratrol (Res). ZnO-loaded NCFDs exhibited dramatically high antibacterial rates exceeding 99% against both <i>Escherichia coli</i> (<i>E. coli</i>) and <i>Staphylococcus aureus</i> (<i>S. aureus</i>). Additionally, all NCFDs, regardless of ZnO and Res loading, demonstrated excellent biocompatibility for human dermal fibroblasts (HDFs) and superior hemostatic performance in a mouse liver bleeding model. The in vivo experiments revealed that the incorporation of ZnO and Res significantly promoted the wound healing process. Specifically, the wound closure rate of mPCL + 0.5%ZnO/nPCL + 8%Res NCFD reached 93.7 ± 0.6% after 10 days of treatment. The regenerated skin tissues displayed enhanced collagen deposition, improved epithelial regeneration, and neovascularization. The mPCL + 0.5%ZnO/nPCL + 8%Res NCFD was also found to significantly stimulate macrophage polarization toward the M2 phenotype, thereby reducing inflammation levels at the injury site. This study provides a novel routine to develop mPCL + ZnO/nPCL + Res NCFDs with innovative structure and appropriate biofunctions, demonstrating potential in wound treatment and skin tissue engineering.