Schiff Base Hydrogel Bio-Adhesive Using Oxidized Chondroitin Sulfate and Polyethylenimine with Antibacterial Properties and Cytocompatibility

Abstract

Hydrogel bio-adhesives have gained great attention in wound healing and tissue regeneration applications because conventional wound closures are often hindered by insufficient adhesion and poor biocompatibility. Considering that dynamic covalent interactions facilitate robust wet adhesion in hydrogels, we fabricated a Schiff base hydrogel bio-adhesive based on oxidized chondroitin sulfate (OCS) and polyethylenimine (PEI), and employed different degrees of OCS oxidation to regulate the physicochemical properties of the bio-adhesives. In this system, aldehyde groups of OCS react with amino groups of PEI to form covalent imine crosslinks, while physical hydrogen bonds also contribute as supplementary interactions. The fabricated hydrogel bio-adhesives demonstrated a three-dimensional interconnected microstructure and regulated equilibrium swelling ratios. The rheological tests also confirmed the typical viscoelasticity of the hydrogels and their shear-thinning behavior. The obtained hydrogel bio-adhesives demonstrated rapid and autonomous self-healing ability and strong adhesion to the surfaces of various matrices and wet organs, including wood, glass, metal, plastic, rubber, and heart, liver, spleen, stomach, and lung tissue. Furthermore, an ABTS radical scavenging assay confirmed their potent antioxidant activity. The hydrogels possessed effective antibacterial activities against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. The hydrogels exhibited good hemocompatibility, effective intracellular reactive oxygen species (ROS) scavenging activity, favorable cytocompatibility, and promoted cell proliferation. These results confirmed the fabricated hydrogels via Schiff base connections for biomedical applications and provided a facile design for biomedical hydrogel bio-adhesives.