Network structure and enzymatic degradation of chitosan hydrogels determined by crosslinking methods.

Polysaccharides can be modified by reactive functional groups to enable chemical crosslinking. We studied how different methods of crosslinking methacrylate-functionalized chitosan affected the network structures and various properties relevant for utilization of the chemically crosslinked hydrogels in biomedical applications, including tissue engineering and delivery of therapeutic agents. Four chitosan hydrogels were made by either the free radical polymerization with varying initiation kinetics and an addition of chain transfer agents or the based-catalyzed Michael-type addition reaction. Four chitosan hydrogels having identical polymer fractions at equilibrium swelling exhibited marked differences in shear moduli, dextran diffusion rate, and especially enzymatic degradation behaviors. Hydrogels made by the free radical polymerization with no chain transfer agent were highly resistant to complete degradation by enzyme for an extended period. We inferred that such resistance originated from chain bundles characterized by densely branched networks of chitosan chains, which was determined by small-angle X-ray scattering analysis.