Rosmarinic Acid-Grafted Dextran/Gelatin Hydrogel as a Wound Dressing with Improved Properties: Strong Tissue Adhesion, Antibacterial, Antioxidant and Anti-Inflammatory.

Designing a strong tissue adhesive and multifunctional hydrogel dressing for various skin injuries is still a significant challenge. Based on the bioactive activities of rosmarinic acid (RA) and its catechol structure being similar to dopamine, RA-grafted dextran/gelatin hydrogel (ODex-AG-RA) was designed and systemically characterized in this study. The ODex-AG-RA hydrogel exhibited excellent physicochemical properties, including fast gelation time (61.6 ± 2.8 s), strong adhesive strength (27.30 ± 2.02 kPa) and enhanced mechanical properties (1.31 × 104 Pa of G'). The examination of hemolysis and co-culturing with L929 cells showed the strong in vitro biocompatibility of ODex-AG-RA hydrogels. The ODex-AG-RA hydrogels exhibited a 100% mortality rate against S. aureus and at least 89.7% against E. coli in vitro. In vivo evaluation for efficacy in skin wound healing was carried out in a rat model of full-thickness skindefect. The amount of collagen deposition and CD31 on wounds in the two ODex-AG-RA-1 groups on day 14 was 4.3 times and 2.3 times of that in the control group, respectively. Furthermore, the mechanism of ODex-AG-RA-1 for promoting wound healing was proved to be related to its anti-inflammatory properties by adjusting the expression of inflammatory cytokines (TNF-α and CD163) and reducing the level of oxidative stress (MDA and H2O2). Overall, this study demonstrated the wound-healing efficacy of RA-grafted hydrogels for the first time. ODex-AG-RA-1 hydrogel, due to its adhesive, anti-inflammatory, antibacterial and antioxidative activities, was a promising candidate as a wound dressing.