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

Abstract

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.

Hydrogels in Cutaneous Wound Healing: Insights into Characterization, Properties, Formulation and Therapeutic Potential

“…This polymer is hydrophilic, biodegradable, highly biocompatible, non-toxic, and non-immunogenic [ 158 , 159 , 160 , 161 , 162 , 168 , 169 , 170 ]. In addition to being sustainable, it is safe [ 171 ] and eco-friendly [ 133 , 172 , 173 ], and is well known for its low cost and wide natural abundance [ 130 , 160 , 161 , 162 , 167 , 173 ].…”

“…In addition, this naturally derived material is promising for soft tissue engineering due to its similarity to the native ECM [ 158 ]. It can provide nutrients and essential elements for tissue regeneration and support cell proliferation [ 168 ].…”

“…However, pure dextran hydrogels present some limitations, particularly concerning low mechanical strength, weak tissue adhesion, poor drug loading ability, and undesirable degradation, which chemical and physical modifications help to overcome [ 167 , 168 ].…”

Therapeutic Potential and Mechanisms of Rosmarinic Acid and the Extracts of Lamiaceae Plants for the Treatment of Fibrosis of Various Organs

“…The topical application of a 10% RA cream enhanced the wound size reduction more effectively compared to a 5% dexpanthenol cream application or nontreatment, which resulted in fewer scars. An oxidized dextran/amidated gelatin hydrogel, "ODex-AG", and an RA-grafted hydrogel, "ODex-AG-RA", were developed as dressings for skin injuries [94]. Both the "ODex-AG" and "ODex-AG-RA" hydrogels promoted skin wound healing in a rat model of a full-thickness skin wound.…”

“…In addition, bioengineering technologies are being developed to increase the RA content in plants and RA production efficiency [137,138]. Furthermore, research on formulations, such as nanoparticles and hydrogels, that increase RA bioavailability or its pharmacological efficacy is also emerging [82,91,94,139,140]. Advances in these related fields will accelerate the industrial and medical utilization of RA.…”