| Hydrogels can simulate the structure and property of extracellular matrix due to their ability to absorb water or biofluid,thus having potential applications in drug release,cell culture and tissue engineering.However,the preparation of hydrogels usually requires complicated process to synthesize functional monomers,and the prepared hydrogels often behave single functionality.In addition,the sudden release or the lack of stimulus-responsiveness during drug release might limit their application in the biological field.To solve these problems,this paper aims to prepare hydrogels with different crosslinking structures through simple and rapid methods,and realize the controlled and stimulus-responsive drug release by regulating the crosslinking network,at the same time study the pH-sensitivity,self-healing property and shape memory property of hydrogels.Firstly,physically crosslinked hydrogels were prepared and their drug release behavior was studied.Then,to solve the problem of sudden drug release from physically crosslinked hydrogels,hydrogels based on acylhydrazone and hydrogen bonds were designed and prepared.The drug release behavior of hydrogels was regulated by changing the crosslinking structures,and these hydrogels behaved pH-sensitivity,self-healing property and shape memory property.The main work of this paper is as follows:Firstly,the functional monomers of diacetone acrylamide(DAAM)and acrylamide(AAM)were used to copolymerize through in situ free radical polymerization,thus preparing physically crosslinked hydrogels based on hydrogen bonds,hydrophobic interaction and chain entanglement through one-step method.The intensity of three different van der Waals forces were regulated through adjusting DAAM content and the effects of DAAM content on the swelling behavior,mechanical property and elastic self-recovery property of hydrogels were studied.The results showed that the mechanical property of hydrogel was the best when DAAM:AAM was 1:9(mol:mol).Studies on the drug release behavior demonstrated that the hydrogels behaved sudden release when releasing small molecule drug of doxorubicin(DOX),while they showed controlled release behavior when releasing macromolecular drug of bovine serum albumin(BSA),and the release ratio of BSA was about 80%after 40 h.Secondly,in order to address the problem of sudden drug release from physically crosslinked hydrogels,the hydrogels based on acylhydrazone and hydrogen bonds were designed and prepared.The acylhydrazine groups could react with the carbonyl groups of DOX to form dynamic acylhydrazone bonds,thus realizing the stable load and controlled release of DOX.Adipic dihydrazide modified alginate(ALG-ADH)and dialdehyde-terminated PEG(PEG-CHO)were synthesized respectively.Taking advantage of the Schiff-base reaction between them and the hydrogen bond interaction between the carboxyl groups of protonated alginate,the modified alginate hydrogels based on acylhydrazone and hydrogen bonds were prepared through one-step method.The crosslinking density of hydrogel was regulated through adjusting PEG-CHO content,and the effects of PEG-CHO content on the gelation kinetics,mechanical property and self-healing property of hydrogels were investigated.The results showed that the hydrogel had the highest mechanical strength and the best self-healing property when PEG-CHO content was 5 wt%.The tensile test demonstrated that the self-healing efficiency of hydrogel could reach up to 85%.The drug release test showed that the modified alginate hydrogel exhibited similar drug release behavior in PBS solution with different pH values,and the drug release ratio was about 30%after 24 h.Furthermore,the acylhydrazone and hydrogen bond crosslinking networks were regulated to solve the problem of low drug release ratio and non-responsiveness of hydrogels.During the copolymerization of DAAM and AAM,not only physically crosslinked network could be formed,but also the introduced functional carbonyl groups could react with hydrazine-type crosslinking agents to form dynamic acylhydrazone bonds.Therefore,the multi-crosslinked hydrogels could be prepared when introducing crosslinking agents into the copolymerizing system of DAAM and AAM.A series of modified polyaspartic acid,namely polyaspartic hydrazine-co-aspartic acid(PHA),were synthesized through ring opening of polysuccinimide with hydrazine hydrate and sodium hydroxide.The structure,molecular weight and acylhydrazine/carboxyl content were characterized by 1H NMR,FTIR,GPC and colloid titration method.Then,PHA was introduced into the DAAM/AAM system to prepare hydrogels based on acylhydrazone bonds,hydrogen bonds and hydrophobic interaction through one-step method.The crosslinking structures of hydrogels were regulated through adjusting the structure and content of PHA polymers,and the effects of PHA on the swelling behavior and mechanical property of hydrogels were investigated.The results showed that the mechanical property of hydrogel was the best when PH2A8 content was 0.1 mol%.The drug release test showed that the DAPHA hydrogels exhibited pH-sensitivity during drug release process.In PBS solution with pH value of 5,the hydrogel showed the fastest drug release rate and the highest drug release ratio,and the drug release ratio was about 65%after 120 h.In addition,the carboxyl groups in PHA polymer endow hydrogels with the ability to complex metal ions,thus giving the hydrogel shape memory property.In 2 M ferric chloride solution,the shape memory time,shape memory ratio and shape recovery ratio were 30 min,50%and 70%,respectively.Finally,in order to further increase the drug release ratio and improve the functionality of hydrogels,the networks of hydrogel were further regulated.Taking advantage of the Schiffbase reaction between poly(diacetone acrylamide-co-acrylamide-co-acrylic acid)(PDAAc)and modified polyethylene glycol(PEGDH)and the hydrogen bond interaction between acrylic acid and protonated alginate,hydrogels based on acylhydrazone and hydrogen bonds were prepared through one-step method.The crosslinking density of hydrogen bonds was regulated through adjusting alginate content and the effects of alginate content on the swelling behavior and mechanical property of hydrogels were investigated.The results showed that the mechanical property of hydrogel was the best when alginate content was 1.38%.Taking advantage of the dynamic and reversible property of acylhydrazone and hydrogen bonds,the self-healing property of hydrogel was studied.The tensile test demonstrated that the selfhealing efficiency of hydrogel could reach up to 85%after about 30 min.The research of pHsensitivity showed that the hydrogel not only exhibited obvious gel-sol transformation under different pH values,but also showed pH-sensitivity drug release behavior.In PBS solution with pH value of 5,the hydrogel showed the fastest drug release rate and the highest drug release ratio,and the drug release ratio was near 100%after about 4 h.In addition,the carboxyl groups of acrylic acid and alginate endow hydrogels with the ability to complex metal ions,thus giving the hydrogel shape memory property.In 1 M ferric chloride solution,the shape memory time,shape memory ratio and shape recovery ratio were 2 min,100%and 100%,respectively. |
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