Studies On Construction And Property Of Pullulan-gelatin-based Hydrogels

Hydrogels have been gradually deeply researched and applied in the field of drug delivery and tissue engineering.In order to make hydrogels more suitable for biomedical applications,polysaccharides and proteins,with appealing biodegradable and biocompatible properties,are selected as raw materials.In this thesis,pullulan and gelatin were used as hydrogels matrix,activated and crosslinked by 1,1 '-carbonyldiimidazole.Different results could be obtained based on various synthesis routes.(1)"Multi-step" synthesis of pullulan-gelatin-based nano-hydrogels.The hydroxyl groups of pullulan molecules were activated by 1,1 '-carbonyldiimidazole(CDI)in anhydrous solvent and reacted with vitamin B6 to obtain pullulan bio-crosslinking agent(PLPP),of which the aldehyde groups reacted with the amino groups of gelatin through Schiff base forming imine crosslinking sites.Then pullulan-gelatin-based nano-hydrogels could be synthesized.The synthesis and gelation processes were characterized and analyzed by amino acid analysis,nuclear magnetic resonance spectroscopy,ultraviolet-visible spectroscopy and transmission electron microscopy.(2)"Two-step" synthesis of pullulan-gelatin-based bulk hydrogels.The hydroxyl groups of pullulan were first activated by 1,1'-carbonyldiimidazole(CDI)in anhydrous solvent and then reacted with amino and hydroxyl groups of gelatin.In this case,pullulan-gelatin-based bulk gels could be synthesized after "Two-step",which are activation and crosslink.The reaction proceeded for at least 24 hours,and crosslinking sites were carbamate and carbonate groups.(3)"One-step" synthesis of pullulan-gelatin-based bulk hydrogels.Pullulan and gelatin were dissolved in dimethyl sulfoxide(DMSO),followed by addition of CDI,acting as a crosslinking agent to react with hydroxyl groups of pullulan,and amino groups,hydroxyl groups and carboxyl groups of gelatin molecules,yielding crosslinking sites of carbamate,carbonate and ester groups.The gel formation could be observed after 4 hours.The polysaccharide-protein gel prepared by "one-step" method exhibited the advantages of simple experimental process,short gelation time,high mechanical strength and excellent stability.The testing results revealed that the property of the gel produced by traditional "two-step" method is inferior to that by "one-step" method.In addition,"one-step" method was used to prepare the pullulan hydrogel with excellent mechanical and biodegradable properties,which was suitable for further tissue engineering application.