Fabrication of a Multilayered Gradient Self-Crosslinking Chitosan Hydrogel by a Controlled Freeze-Melting-Neutralization Method

Chitosan (CS) physical hydrogels without external cross-linkers are attractive materials for biomedical applications owing to their biodegradability and biocompatibility. In the present study, multilayered self-crosslinking CS hydrogels with gradient structures were fabricated by a controlled freeze melting-neutralization method. The microstructure and properties of hydrogels can be adjusted by changing the relationship between melting rate and neutralizing rate of frozen CS samples through not only the freezing temperature and concentration of the CS solution but also the concentration and temperature of the NaOH neutralization solution. Using bovine serum albumin as a model protein, in vitro drug release studies indicated that the release profile was influenced by the CS hydrogel microstructure. These results suggest that multilayered self-crosslinking CS hydrogels can be fabricated by a simple freeze-melting-neutralization method and can serve as effective scaffolds for tissue engineering.National Natural Science Foundation of China [81200814]; National Key Technology R&D Program of China [2012BAI22B03]SCI(E)ARTICLE3232-238