Study On The Influence Of Amino Acid Residue Chirality On The Structure And Properties Of Polypeptide Hydrogel Materials

Hydrogel is a kind of three-dimensional network material formed by polymer cross-linking,which can swell in water rather than dissolve.Hydrogels usually have high water content,good biocompatibility,convenience of manufacturing,variable composition and ideal physical properties,which make it a candidate with good potential in the field of biomedicine.Polypeptide hydrogels have good biocompatibility and biodegradability,as well as structures similar to the original extracellular matrix,and they have received more and more attention in the biomedical application.Polypeptides have unique secondary structures,which have a significant impact on the multiple properties of polypeptide hydrogels.By adjusting the residue components,length of polypeptide segments,side groups or end groups,the secondary structure and properties of polypeptide hydrogels can be effectively controlled.However,researches on the properties of hydrogels based on the chiral modulation of residues of polypeptides and their derivatives are limited yet.Therefore,based on the adjustment of the chirality of the amino acid residues in the polypeptide segments,we designed three types of poly(ethylene glycol)-polypeptide block copolymers,and studied the effects of the adjustment of the polymer structures from different perspectives on the performance of polypeptide hydrogels:1.The influence of the content of amino acid residues with different chirality on the performance of temperature-sensitive polypeptide hydrogels.We synthesized mPEG-polypeptide diblock copolymers with different residue contents of y-ethyl-Lglutamate(ELG)and/or y-ethyl-D-glutamate(EDG),and prepared a thermosensitive hydrogels.We proved that the properties of polypeptide thermosensitive hydrogels can be effectively controlled by adjusting the chirality of the residues and the secondary structure of copolymers,and the contents of chiral glutamic acid residues will also affect the biodegradability,as well as the inflammatory response of the hydrogels.2.The effect of polypeptide block sequence on the performance of thermosensitive polypeptide hydrogels.We synthesized two mPEG-polypeptide triblock copolymers EG45ELG8.2(ELG0.5EDG0.5)8.2 and EG45(ELG0.5EDG0.5)7.9ELG7.9 containing different polypeptide block sequences.The copolymer EG45(ELG0.5EDG0.5)7.9ELG7.9,whose ELG-co-EDG blocks are linked to the PEG blocks,showed better gelation performance than the copolymer EG45ELG8.2(ELG0.5EDG0.5)8.2.We proved that the secondary structures of the copolymers can be adjusted by tuning the block sequence of the chiral polypeptide block within the copolymers,thereby the properties of the polypeptide thermosensitive hydrogels can be effectively controlled.3.The influence of copolymer topologies and amino acid residue chirality on the degradation performance of polypeptide enzyme-crosslinked hydrogels.Our research is based on the PEG/polypeptide block copolymers with different topological structures of copolymers and residue chirality in polypeptide chains,which were synthesized in the previous research.The results showed that the degradation rates of copolymers and hydrogels composed of D-glutamic acid units are significantly lower than the samples composed of L-glutamic acid structural units,and the topological structure of the copolymers also affected the degradability of poly(L-glutamine acid)-based hydrogels.In vivo biodegradability and biocompatibility studies have shown that the topological structures of the copolymers and the chirality of amino acid residues in the polypeptide segments will significantly affect the degradation behaviors and inflammatory response of the hydrogels in vivo.This study provides new insights into the influence of the topological structures of the copolymers and the chirality of amino acid residues on the hydrogel properties,biodegradability and biocompatibility of polypeptide-based hydrogels.