Design and Synergistic Antibacterial Performance of Cyclodextrin Reinforced Chondroitin Sulfate/Carboxymethyl Chitosan Dual-network Hydrogel Dressing

Herbal extracts possess antioxidant and broad-spectrum antibacterial activity, which can efficiently inhibit the growth of multiple pathogenic microorganisms. However, their inherent disadvantages, including poor aqueous solubility and inferior physicochemical stability, severely hinder their practical application. Herein, a co-loaded dual-network polysaccharide hydrogel was engineered to tackle these challenges. Baicalin (BA) was first encapsulated into cyclodextrin to yield a BA inclusion complex, which was embedded within a crosslinked hydrogel network built from chondroitin sulfate and carboxymethyl chitosan. Berberine hydrochloride (BH), a synergistic antibacterial candidate, was co-loaded in situ during hydrogel synthesis to attain combined antibacterial effects of baicalin and berberine hydrochloride. The antibacterial results confirm that the BH-BA inclusion complex effectively lowers the individual effective antibacterial concentrations of both agents, showing prominent synergistic activity against Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive). The resultant hydrogel displayed enhanced structural stability, favorable mechanical properties, excellent biocompatibility, as well as pH-responsive drug release profiles. After incubation with the dual-network hydrogel, the survival rates of Escherichia coli and Staphylococcus aureus reached 12.67 ± 3.06% and 7.33 ± 2.08%, respectively, accompanied by a DPPH radical scavenging capacity of 82.08± 6.99%. Among all tested groups, the OCBBC group displayed the most pronounced effect in promoting cell migration, achieving a cell scratch wound healing rate of 72.46 ± 1.75%. This dual-network hydrogel provides a feasible avenue to construct high-efficiency antibacterial biomaterials and paves the way for innovative antibacterial treatment modalities.