Fabrication and evaluation of chitosan/gelatin/PVA nanofiber incorporating Dihydroartemisinin for wound healing applications: An in vitro, in vivo study.

Dihydroartemisinin (DHA) has recently demonstrated potential for promoting infected wound healing, but its topical application is limited by poor solubility and the inadequacy of conventional formulations. To address these challenges, we developed a novel electrospun nanofiber membrane based on a high-concentration Gelatin/Chitosan/Polyvinyl alcohol/Gum arabic (Gel/CS/PVA/GA) composite for the sustained delivery of DHA. The formulation was systematically optimized. The resulting GCP0.4A0.05 composition (Gel and CS, along with 0.4 g PVA and 0.05 g GA) exhibited uniform nanofiber morphology, excellent porosity (80-90%), balanced mechanical properties, and appropriate hydrophilicity. To enhance structural stability, an innovative pre-spinning physical crosslinking strategy using sodium tripolyphosphate (STPP) and borate was employed, significantly improving water resistance and mechanical strength while preserving the porous architecture. The DHA-loaded membrane demonstrated excellent biocompatibility, potent broad-spectrum antibacterial activity against S. aureus and E. coli, and accelerated wound closure in a rat full-thickness defect model. Histological analysis revealed reduced inflammation (CD68+ macrophages), enhanced angiogenesis (CD31+ vessels), and well-organized dermal regeneration. Collectively, these findings lead to the development of a novel topical formulation for DHA, harnessing a multifunctional nanofibrous membrane to pave a new way for effective chronic wound management.