Citric Acid-Modified Chitosan Hydrogel Loaded With Shikonin Promotes Skin Wound Healing.

Abstract

BACKGROUND: Despite the advancements of pharmacological treatments and gauze dressings in the field of skin wound healing, these methods present numerous limitations. Therefore, developing a multifunctional material capable of efficiently promoting skin wound healing is particularly crucial. METHODS: Citric acid (CA)-modified chitosan (CS) loaded with shikonin (SK) (CA-CS-SK) hydrogel was prepared via the freeze-thaw method. The physical properties of the hydrogel were profiled through Fourier transform infrared spectroscopy, SEM, rotational rheometry, swelling experiment, degradation rate analysis, and drug release experiments. Furthermore, the biocompatibility of the hydrogel was comprehensively evaluated through hemolysis assay, CCK-8 cytotoxicity detection, and live/dead cell staining. Antimicrobial activity against Escherichia coli and Staphylococcus aureus of the hydrogel was gauged in vitro, and its therapeutic performance was ultimately validated in a mouse full-thickness wound model through hematoxylin and eosin staining and enzyme-linked immunosorbent assay. RESULTS: The CA-CS-SK hydrogel exhibited appropriate rheological properties, swelling ratio, degradation rate, and drug release rate. It effectively suppressed the proliferation of E coli and S aureus, with superior inhibitory effects compared to CA-CS hydrogel and SK alone. In addition, the hydrogel showed no significant toxicity to human dermal fibroblasts and did not cause erythrocyte rupture. Animal model experiments demonstrated that, compared to cotton gauze, CA-CS hydrogel, and SK, the CA-CS-SK hydrogel reduced levels of tumor necrosis factor-α and interleukin-6 at the wound site, alleviated the inflammatory response, and promoted wound healing. CONCLUSION: The CA-CS-SK hydrogel possesses high antibacterial activity, excellent biocompatibility, and efficient wound healing promotion capabilities, making it a highly promising material for skin wound treatment.