Spray-drying-engineered CS/HA-bilayer microneedles enable sequential drug release for wound healing

High incidence and mortality rates of chronic wounds place a heavy burden on global healthcare systems. Achieving phased delivery of antimicrobial and regenerative drugs is crucial for promoting chronic wound healing. Herein, a microneedle (MN) patch with a biphasic release system was developed using a combination of solvent casting and spraying methods. Additionally, a copper/PDMS mold was introduced to address the issue of deformation in the chitosan material during drying on polydimethylsiloxane (PDMS). The MNs have a bilayer structure, with a hyaluronic acid (HA) coating loaded with doxycycline (DOX) for antibacterial action and a chitosan (CS) core loaded with vascular endothelial growth factor (VEGF) for promoting cell migration and proliferation. Notably, <i>in vitro</i> drug release studies showed that the coating drug was released by 98.8% within 10 hours, while the release of the core drug could be sustained for up to 70 hours. <i>In vivo</i> studies showed that chronic wounds on C57 mice treated with CS/HA-bilayer MNs achieved nearly complete healing by day 9. These wounds exhibited reduced inflammatory cell infiltration, increased epithelial tissue regeneration, and enhanced collagen deposition. This work integrates the staged management of bacterial infection and angiogenesis and offers promising prospects for enhancing chronic wound healing.