Effects of Crosslinking Methods on Network Structure and Enzymatic Degradation of Methacrylate-Functionalized Chitosan Hydrogel

Polysaccharides, such as hyaluronic acid, alginate, or chitosan, can be modified by addition of reactive functional groups to enable chemical crosslinking. Here, we studied how different methods of crosslinking methacrylate-functionalized chitosan affected the network structures of the resulting hydrogels. We then investigated how the porous network structures in turn influenced stiffness, macromolecular diffusion through the pores, and enzymatic degradation. All these properties are relevant for utilization of the chemically crosslinked hydrogels in biomedical applications, including tissue engineering and delivery of therapeutic agents. We made chitosan hydrogels using four crosslinking methods, which differ by type and by reaction kinetics. We found that four chitosan hydrogels having identical polymer fractions at an equilibrium swelling exhibited marked differences in their shear moduli, rate of dextran diffusion, and especially their enzymatic degradation behaviors. We inferred that these differences originated in variations among network structures, which were characterized by the formation of chain bundles and associated network heterogeneity as determined by small-angle X-ray scattering analysis.