Chronic wounds and persistent infections necessitate innovative biomaterials that simultaneously enhance tissue regeneration and prevent microbial colonization. In this study, we developed a biocompatible hydrogel system incorporating imidazolium-based ionic liquids (ILs) for the dual delivery of carnosic acid (CA) and madecassoside (MD), leveraging their complementary therapeutic properties. The hydrogel matrix, formed by crosslinking chitosan and gelatin in the presence of ILs, was co-loaded with CA and MD at a total drug content of 2%. Mechanical testing revealed that the inclusion of ILs significantly enhanced structural integrity, with the storage modulus reaching up to 33 kPa and compressive strength exceeding 50 kPa, outperforming IL-free counterparts (Mir et al., 2020).

Drug release profiles demonstrated a biphasic pattern, with an initial burst release of 20–30% within the first 8 hours, followed by sustained release over 72 hours. Cytocompatibility evaluations via MTT assays on L929 fibroblasts indicated high cell viability (>85%), confirming the safety of the IL-polymer system. Furthermore, in vitro scratch assays revealed markedly improved wound closure rates in formulations enriched with madecassoside. At 24 hours, MD-rich hydrogels achieved approximately 52% wound closure, significantly outperforming lower-MD variants and the control group, which showed only 18.7% closure.
These results underscore the synergistic benefits of CA’s antioxidant and antimicrobial effects with MD’s pro-regenerative properties in an IL-enhanced hydrogel. This system offers a safe, mechanically robust, and tunable platform for local drug delivery, presenting a promising solution for advanced wound management and opening avenues for further research into multifunctional biopolymer networks.