Synthesis,preparation And Properties Of Biomimetic Biomaterials Based On Glycopolypeptides

Tissue or organ failure is usually difficult to heal itself,severely affecting people's quality of life and even life-threatening.Current therapies including organ transplantation,surgery,artificial prostheses and mechanical devices,are hard to satisfy patients' needs for major damage.Tissue engineering(TE)as a complementary treatment or an alternative,combines biomaterials,cells and biological molecules toward the construction of engineered tissues that restore,replace or improve damaged tissues.However,a lack of biomaterials with appropriate chemical,physical and biological properties hampers the clinical success of TE.Biomaterials not only provide support for cells but also direct cell behaviors in the process of tissue formation and regeneration.More specifically,biomaterials should have appropriate biocompatibility,biodegradation,mechanical properties,microenvironments that are suitable for the delivery of nutrients,gases,proteins,etc.,bioactivity and architecture.The ability to mimic structures and functions of glycoproteins or glycosaminoglycans possibly makes glycopolypeptide-based biomaterials satisfy these requirements.To build biomaterials based on glycopolypeptides,this dissertation studied the influence of chemical structures on the secondary structures,degradation,mechanical properties,biocompatibility and so on of glycopolypeptides from the view of structure-property relationship.Detailed research contents and main findings were listed as below.(1)Here,we prepared three in situ-forming hydrogels from phenol functionalized glycopolypeptides(galactosylated,glucosylated or mannosylated)in the presence of H2O2 and horseradish peroxidase.The gelation time,mechanical properties,in vivo degradation,and biocompatibility of these hydrogels were assessed to evaluate their potential as biomaterials.Gelation time ranged from 11 to 380 s,depending on the concentration of horseradish peroxidase.The mechanical properties were dependent on the monosaccharide of the glycopolypeptide hydrogels.The glycopolypeptide hydrogels were completely degraded about 21 days,and exhibited favorable biocompatibility.Immune response was also subjected to the monosaccharide of the glycopolypeptide hydrogels.The above results indicated glycopolypeptides are appealing building blocks for biomaterials.(2)Here,we synthesized a range of galactosylated poly(?-propargyl-L-glutamate)s with different lengths and investigated the secondary structures,enzymatic degradation,bioactivity and biocompatibility of them.The glycopolypeptides predominantly adopted ?-helical conformation.The helicity increased over the degree of polymerization of the polypeptide backbones(24 to 44)and slightly decreased with further increase of the degree of polymerization of the polypeptide backbones(44 to 68).Galactosyls in glycopolypeptides tended to hinder the enzymatic degradation of them by steric effects.The glycopolypeptides were bioactive and biocompatible.(3)Here,we synthesized a series of glycopolypeptides composed of galactosylated poly(?-propargylglutamate)s containing L-and/or D-glutamate residues.Glycopolypeptides containing pure L-glutamate residues or D-glutamate residues were predominantly ?-helical,but the helical direction was opposite.Apparent random coil conformation was observed for glycopolypeptides with mixed enantiomeric residues,while a small amount of ?-helical conformation remained.The closer the proportion of L-glutamate residues to D-glutamate residues was,the higher the random coil content became.The enzymatic degradation rates of the glycopolypeptides were markedly reduced following the introduction of D-glutamate residues into backbones.Investigations on TE-related properties of glycopolypeptides used as building blocks for biomaterials in this dissertation provided new ideas for the design of biomaterials and valuable data for the performance regulation of glycopolypeptide-based biomaterials.