Electrospun-lyophilized chitosan wound dressings for dual bioactive delivery of hyaluronic acid and IL-6.

Wound healing is a complex and highly regulated cellular process with limited therapeutic interventions despite its substantial clinical burden. Current research shifts towards endogenous biomolecules as promising wound healing candidates, including hyaluronic acid and interleukin-6. However, despite their clinical potential such molecules pose significant technological challenges due to their fragility, limiting their clinical application. To overcome these limitations, a bilayer wound dressing was developed combining electrospinning and freeze drying. A chitosan nanofiber mat serves as a physical barrier, while hyaluronic acid and interleukin-6 were transformed into a hydrophilic wound-healing-promoting layer via freeze drying, enabling immediate and wound-phase-specific delivery of interleukin-6. Hyaluronic acid acts as a stabilizer for interleukin-6, enhancing its recovery by about 30 % and initial storage stability. The wound dressing demonstrates high biocompatibility, with a cell viability of 126 % and reduces the residual wound area and accelerates wound closure by more than 40 % after 48 h compared to the control. Further, pronounced antibacterial activity of chitosan is proven against S. aureus and P. aeruginosa, further enhanced by hyaluronic acid through increased protonation of amino groups. These results provide proof-of-concept for the potential of this bilayer system as a multifunctional platform for the stable and effective delivery of fragile biomolecules enabling modern wound therapy.