Synthesis And Characterization Of Bio-inspired Oligoimine-crosslinked Chitosan Hydrogel

Hydrogel has emerged as a new class of medical dressings and attracted broad attention of academia and industry research due to its superior performance than traditional dressing materials. In this thesis, a novel bio-inspired oligoimine-crosslinked chitosan hydrogel capable of carrying bioactive molecules has been designed and developed. The resultant hydrogel not only can be applied in tissue repairing to deliver anti-inflammatory drugs, but also is able to afford the scaffold for cell growth as a tissue engineering material. First, spermidine, a natural compound found in various organisms, has been chosen as the amino provider with bioactivity. Then terephthalaldehyde has been selected as the source of aldehyde by cytotoxicity experiments to form oligoimine crosslinkers with spermidine. The investigation on the effects of theoretical crosslinker length on the formation of the hydrogel shows an optimized ratio of 1.2:1 for terephthalaldehyde to spermidine. To obtain hydrogel with better performance, the chitosan hydrogels have been prepared in both acidic and alkaline solutions. Morphological characterization has revealed that the chitosan hydrogels contain micron-scale pores surrounded by lamellar structures. The pore size gradually decreases as the chitosan concentration or theoretical cross-linking degree increases. Overall, the hydrogels formed in the alkaline solutions possess better mechanical properties than those prepared in the acidic media. In the acidic system, the hydrogel with theoretical crosslinking degree of 29% exhibits the best performance, whereas in the basic system, the chitosan hydrogel at 2% chitosan concentration and 1.74% of theoretical crosslinking degree shows the optimal mechanical properties with more strength. In order to examine the biological compatibility of oligoimine-crosslinked chitosan hydrogels, cytotoxicity experiments and live cell stainings have been performed. The chitosan hydrogels from both acidic and alkaline systems demonstrate good biocompatibility. Moreover, three drug-loading methods with doxorubicin have been compared, which shows that the hydrogels from both systems are capable of slow-releasing drug delivery. The best slow releasing profile can be achieved by introducing doxorubicin to the crosslinker solution before the curing step with chitosan.