Application Of Glycol Chitosan-based Hydrogels In Tissue Engineering And Drug Delivery

Hydrogel has been extensively studied in the field of tissue engineering and drug delivery, due to their high water content, good biocompatibility and high flexibility parallel of tissues. The first chapter of this thesis gives a general introduction to the structures, properties and application of the common natural polymer materials and synthetic polymer materials used for hydrogels, and addresses the cross-linking stragies, including physical crosslinking and chemical crosslinking.The second chapter describes glycol chitosan-based hydrogels are rapidly formed upon mixing thiolated glycol chitosan and water soluble oligo(acryloyl carbonate)-b- poly(ethylene glycol)-b-oligo(acryloyl carbonate) triblock copolymers at remarkably low solid concentrations of 1.5-4.5 wt.% under physiological conditions. The gelation time and mechanical properties of hydrogels can be nicely tuned by DS of GC-SH, solution pH, and polymer concentration. These microporous glycol chitosan-based hydrogels while rather stable under physiological conditions are subject to enzymatic degradation by lysozyme. Interestingly, these hydrogels are cell non-adhesive, and can be readily made into bioactive extracellular matrix with MG63 and L929 cells attachment and proliferation functions through immobilization with thiol-containing bioactive molecules such as Gly-Arg-Gly-Asp-Cys (GRGDC) peptide via Michael-type addition reaction under physiological conditions. Glycol chitosan is enzymatically degradable in vivo, which offers a significant advantage over PEG and dextran. These rapidly in situ forming enzymatically biodegradable hybrid hydrogels have great potentials in the development of injectable cell-specific bioactive extracellular matrices for tissue engineering.The third chapter describes dual senstive (pH senstive and reduction sensitive) nanogels are developed based on glycol chitosan modified by lipoic acid and 1,2-cyclohexanedicarboxylic anhydride and applied for controlled release of doxorubicin (DOX) w. The lipoic acid provides the hydrophobic group used for micelle preparation, and S-S bonds used for the reduction-triggered release of DOX and nanogel cross-linking with a catalytic amount of dithiothreitol (DTT). The crosslinking can improve the nanogel's stability against dilution, a high salt concentration and an organic solvent.. The chitosan was modified by the 1,2-cyclohexanedicarboxylic anhydride, which reacted with the amino group to produce an amide bond and a carboxylic acid group. The resultant amide is relatively stable at neutral (normal physiological condition) and alkali pH values, but degrades promptly under slightly acidic conditions (e.g. endosome, lysosome) to expose positively charged amino groups again. : The nanogel can package doxorubicin with high encapsulation efficiency. In vitro release studies show that the release of doxorubicin is pH and reduction-responsive. For example, only 25 % DOX was released from GC-LA4.1-CCA76 nanogel after 35 hours under pH 7.4; but, 100 % DOX was released in 35 hours under pH 5.0 and 100 % DOX was released in 30 hours in the presence of 10 mM DTT under pH 7.4. Therefore, these smart naogels have tremendous potential for tumor-targeted chemotherapy.