Synthesis and characterization of an enzyme-degradable zwitterionic dextran hydrogel

Abstract

The interest in dextran hydrogels for soft tissue engineering has increased due to their great biocompatibility and capability to reduce nonspecific protein adsorption and cell attachment. However, these properties are not sufficient for dextran hydrogels to fulfill their role to work as a tissue engineering scaffold candidate. In addition, the scaffold should have controllable degradability and functionality to conjugate bioactive moieties to facilitate tissue growth and regeneration. Therefore, a peptide cross-linked, enzyme degradable zwitterionic carboxybetaine functionalized dextran (CB-Dex) hydrogel was synthesized and studied. After the incorporation of the carboxybetaine group into dextran, the dextran hydrogel obtained excellent antifouling properties to resist the attachment of bovine aortic endothelial cell (BAEC) adhesion with a surface density as low as 5.5 × 10² per cm² and meanwhile CB-Dex does not compromise the low toxicity of natural dextran. In addition, the CB-Dex hydrogel was hydrolytically stable in PBS solution and can be degraded completely within 8 hours when exposed to 0.1 mg mL⁻¹ of collagenase. Moreover, the zwitterionic hydrogel was functionalized with the cell-adhesion peptide (Arg-Gly-Asp (RGD)) and found to enhance cell adhesion with the cell coverage density increased to 1.3 × 10⁴ per cm². Together, these data suggest that the matrix metalloproteinase peptide cross-linked zwitterionic hydrogel with RGD would be advantageous in tissue engineering scaffold applications.