An ideal material for wound healing must be biocompatible, biodegradable, easily applicable, highly stable and able to protect the wound from infection. One of these biomaterials, which are attracting huge attention in recent years, are smart polymeric networks of biobased hydrogels. Chitosan (CHI) is a natural biopolymer of great interest, as it can be successfully applied in wound healing biomaterials with desirable and adjustable properties. In addition, chitosan possesses capabilities to aid the healing process and its unique beneficial properties: biodegradability, high biocompatibility, non-toxicity, mucoadhesiveness, antioxidant, anti-inflammatory, antifungal and antibacterial.

Chitosan-based hydrogels (CHI) promote wound healing and alleviate chronic inflammation and infections. However, in difficult-to-heal ulcers with excessively painful inflammation, the anti-inflammatory activity of hydrogels can be enhanced by sustained release of non-steroidal anti-inflammatory drugs or in combination with antibiotics. Thus, i+Med has cross-linked CHI with genipin (GP) to obtain biocompatible hydrogels. Furthermore, this article confirms the antibacterial activity of CHI with genipin (GP) against Staphylococcus aureus and Escherichia coli with almost 100% bacterial reduction and potential antibacterial efficacy (R > 2).

Effective healing of ulcerated wounds with hydrogels was demonstrated with a significant improvement in metabolic activity of 95.58% (± 4.40%), collagen and elastin amounts (1.48μg ± 0.07 μg collagen and 5.82μg ± 0.73 μg elastin per mg dermal tissue) and histological analysis. Finally, the sustained release of acetylsalicylic acid (ASA), cefuroxime (CFX), tetracycline (TCN) and amoxicillin (AMX) and their anti-inflammatory activity were studied. The results confirm the synergistic anti-inflammatory activity by significantly reducing the amount of proinflammatory cytokines when ASA was combined with CFX (5.39 ± 0. 81 ng-mL-1 TNF-α), TCN (4.70 ± 0.21 ng-mL-1 TNF-α and 49.06 ± 9.64 ng-mL-1 IL-8) and AMX (2.28 ± 0.36 ng-mL-1 TNF-α, 14.84 ± 5.57 ng-mL-1 IL-8 and total elimination of IL-6).