Preparation Of Hydrogels And Their Application To Control Protein Release

Hydrogels are a kind of soft material,consisting of three-dimensional polymer networks and lots of water.Because of the likeness between the biological tissue,the typical response and swelling and so on a series of special properties,hydrogels have been widely used in many fields such as drug delivery system,tissue engineering,electronic sensing and effect device design.But in terms of drug delivery system,because of the large traditional hydrogels have many holes,hydrogels occur burst release on drug release in a short period of time will load hydrogel drug released in full which can not reach the expected goal.Therefore,this paper aims to find a construction that can eliminate the burst release and regulate the release of the drug as needed.(1)In order to rapidly high yield in the physiological conditions obtain complex DNA structural unit(Y-DNA.L-DNA and L '-DNA)without heat treatment,we synthesized a kind of cationic comb graft copolymer-polylysine graft glucan(CCC).CCC not only promotes the efficient self-assembly of DNA structure units,but also can stabilize the multistage structure of the DNA structure unit,especially the formation of complex 3D DNA hydrogels.(2)With the simple functionalization method and good biocompatibility,an aptamer-integrated DNA hydrogel is used as the protein delivery system with adjustable release rate and time by using complementary sequences(CSs)as biomolecular trigger.The aptamer-functionalized DNA hydrogel is simply prepared via one-pot self-assembly process-from-two-kinds of DNA-building blocks(X-shaped and L-shaped DNA units)and a single-stranded DNA aptamer.The gelling process is achieved under physiological conditions within one minute.In the absence of the triggering CSs,the aptamer grafted in the hydrogel exhibited a stable,hybridization state for protein-type-specifical capture.Then in the presence of the triggering CSs,the aptamer is turned into a new hybridization state that leads to the fast dissociation of protein from aptamer with wise-stage controlled release program.The hydrogel is successfully applied to complex matrixes such as human serum and has excellent cytocompatibility.The whole process of protein capture and release is biocompatible and could not refer to any adverse factor to the protein or cells.The aptamer-functionalized DNA hydrogel will be a good candidate for protein controlled delivery.(3)Three-dimensional(3D)bioactive protein-patterned hydrogels provide a more biomimetic environment for cell culture than traditional bioinert scaffolds.However,it has proved difficult to obtain a hydrogel with simultaneously patterned proteins and controlled release at a later stage without inactivating the bioactivity of the fragile proteins.In this study,an aptamer-patterned PEG hydrogel was formed using biorthogonal "click chemistry".The patterned aptamer could selectively capture the bioactive protein based on the specific affinity between the aptamer and protein,which results in the formation of a patterned protein within the hydrogel.More importantly,by adding the complementary DNA strand(cDNA)of the aptamer,the protein can dissociate from the aptamer at any desired time and concentration due to the DNA hybridization.This aptamer-patterned hydrogel could become a smart and biomimetic 3D micro-environment for controlled delivery of proteins simultaneously in a spatiotemporal manner.(4)Various hydrogels have been used as proteins delivery in curing human disease.Nevertheless,it always is difficult to control capture and release of multiple proteins in different regions and periods on the basis of the need of diseases therapy.This research strongly proves that multiple proteins can be captured and released from the aptamer-patterned films with regolabile release rate at prospective time and specific regions utilizing the complementary DNA strand(cDNA)of aptamer via DNA hybridization-The hydrogel film is successfully applied to complex matrixes such as human serum and has excellent cytocompatibility.Thus,the aptamer-patterned hydrogel film can be applied to the programmable release of multiple proteins to cure complicated human diseases.