Fish Scale-derived Chitooligosaccharide and Chitosan Hydrogels as Functional Biomaterials for Wound Healing

Chronic and poorly healing wounds require dressings that do more than provide coverage, but actively regulate infection, oxidative stress, and tissue repair. In this study, hydrogels formulated from fish-scale-derived low-molecular-weight chitosan and chitooligosaccharide (COS) were evaluated using integrated antimicrobial, antioxidant, and in vivo wound-healing analyses to assess their comparative therapeutic performance. Antimicrobial testing against Gram-positive bacteria (Bacillus subtilis and Micrococcus luteus) and Gram-negative bacteria (Aeromonas hydrophila and Klebsiella pneumoniae) showed that COS displayed stronger activity overall, with minimum inhibitory concentrations ranging from 0.156 to 1.25 mg/mL, compared with 0.313 to 1.25 mg/mL for chitosan. COS also showed a clearer bactericidal effect, particularly against the Gram-positive strains, whereas chitosan was predominantly bacteriostatic under the conditions tested. In antioxidant assays, COS demonstrated stronger hydroxyl radical and ABTS radical scavenging activity than chitosan, indicating a more favourable redox-modulating profile. Physicochemical analyses revealed differences in the swelling and degradation profiles of the two hydrogel formulations. In vivo, both hydrogels promoted wound contraction relative to untreated wounds, with COS exhibiting the more rapid response. The COS-treated group achieved complete mean wound contraction by day 14, accompanied by greater collagen-associated staining during subsequent histological assessment. By day 21, the collagen-associated percentages reached 95.71% in COS-treated wounds and 84.81% in chitosan-treated wounds. Immunohistochemical analysis further demonstrated temporal changes in TGF-β1 expression, with increased staining during the proliferative stage of wound repair. Collectively, these findings indicate favourable wound-healing performance of fish scale-derived COS hydrogel relative to chitosan hydrogel under the experimental conditions examined. The results support further investigation of fish scale-derived biopolymers as potential materials for wound dressing development.