Preparation And Properties Of Physically And Chemically Cross-linked Hydrogels Based On Reduction/temperature-responsive PLA Complexation

Since the discovery of polylactic acid complexation in 1987,many releted studies on the synthesis of hydrogels have appeared in biomedical field.Polylactic acid complex crystals have denser packing and stronger intermolecular interactions,which have been proven to be more effective in reinforcing polymer materials.As one of the physical cross-linking methods,polylactic acid-based complex hydrogels are used in many fields such as bioengineering,wound dressings and other applications that are directly contacted and absorbed by the human body due to their high water content and good biocompatibility.Generally speaking,a hydrogel that can respond to the stimulus of the external environment to make corresponding changes in its own properties such as swelling performance,mechanical strength,etc.,is called stimulusresponsive hydrogel.In terms of environment,there is a great difference between the some diseased parts of human body and the normal tissue.As a degradable group,disulfide bonds will quickly break under the highly reducing environment in tumor cells.Recently,the volume phase transition temperature(VPTT)of the randomcopolymer P(MEO2MA-co-OEGMA)which formed by temperature-sensitive monomer MEO2MA andOEGMA can be adjusted accurately from 28?(100%MEO2MA)to 90?(100%OEGMA)by adjusting the content of the two monomers.As a result,the synthesized thermosensitive sensitive hydrogel is more safty.Based on the above background,this article first synthesized a physical crosslinked hydrogel with temperature and reduction responsiveness by introducing redox disulfide bonds and temperature-sensitive monomer MEO2MA,OEGMA.Then in the second part,the physical and chemical double cross-linked reduction/temperature dual responsive hydrogel was synthesized by free radical polymerization of the previous macromonomer,temperature-sensitive monomer and chemical cross-linking agent N,N-bis(acryloylcystamine)(BAC).The way of double crosslinked has greatly improved the mechanical properties of the hydrogel.The specific work is as follows:1.The initiator HSEMA was synthesized through the monoesterification reaction of methacryloyl chloride and 2,2'-dithiodiethanol,and then the initiator and lactide were used for ring-opening polymerization to synthesize the macromonomer HSEMA-PLLA/PDLA.The macromonomer and the temperature-sensitive monomers MEO2MA and OEGMA were subjected to free radical polymerization to synthesize the graft copolymer.Finally,the synthesized chiral graft copolymer solution is mixed in equal amounts to obtain the stereocomplexed reduction temperature responsive nano hydrogel in situ.The structure characterization was carried out using 1H NMR,FT-IR,Raman spectrometer,and XRD to prove the structure of the synthetic substance and the co-crystal of stereocomplexation;Using UV to characterize its light transmittance,low critical solution temperature,and reducibility.The fluorescence probe method confirmed that the nanohydrogel has better stability than the single enantiomer graft copolymer micelle.DLS combined with TEM to analyze the microscopic morphology and particle size changes of the nano hydrogel micelles in different states.Thermal stability analysis and rheological analysis confirmed that the hydrogel has great thermal stability and mechanical properties.Finally,doxorubicin was used as a hydrophobic model to simulate drug release.2.The chemical crosslinking agent N,N-bis(acryloylcystamine)(BAC)was introduced,and the physicochemical double crosslinked hydrogel was synthesized by free radical polymerization.The complexation of the macromonomer HSEMA-PLLA and HSEMA-PDLA synthesized in the first part of the work is used as a physical crosslinking effect,the chemical crosslinking agent BAC is used as a chemical crosslinking effect,and AIBN is used as an initiator to synthesize the physical and chemical double-crosslinked temperature/redox double stimulus responsive hydrogel.Control the amount of chemical crosslinking agent to compare a series of properties of the hydrogel.XRD was used to verify the physical interaction crystals.Through swelling experiments at different temperatures and redox environments,the temperature/redox responsiveness of the hydrogel were studied.The threedimensional network structure of the freeze-dried and swollen gel was clearly observed by using a DSEM.The redox and mechanical properties of the hydrogel were compared and analyzed by UV spectroscopy and dynamic viscoelastic spectrometer.Finally,doxorubicin was used as a hydrophobic drug model to simulate the release of drug-loaded hydrogels in vitro.