Preparation And Characterization Of Stimuli Responsive Self-healing Hydrogel Based On Polypeptides

The stimuli-responsive hydrogels are a three-dimensional physical and/or covalent cross-linking network containing a large amount of water,which exhibits a controlled chemical structure or physical property change under external stimuli.The stimuli-responsive hydrogels can respond quickly and achieve gel-sol conversion in a variety of environments under outside stimuli.Polypeptide hydrogels are prepared by polymerizing biocompatible amino acids,which have great biocompatibility and biodegradability.The hydrophobic cross-linking network formed by utilizing the hydrophobic structure of the amino acid side chain endows hydrogel with injectable self-healing properties,which has great application potential in the field of biomedicine.In this paper,polypeptide with responsive groups was introduced into responsive hydrogels,and their responsive degradation properties and their applications in drug release were investigated.1.A photo-responsive glutamic acid monomer was synthesized by modifying a photo-responsive group o-nitrobenzyl alcohol to glutamic acid.Then the photo-responsive polypeptide was prepared by a novel polymerization method.A photodegradable self-healing hydrogel that is crosslinked by physical hydrophobic interaction can be obtained by dissolving the polypeptide in water.The mechanical properties of hydrogels with different concentrations and hydrophobic block polymerization degree showed that the hydrophobic content and the increase of the degree of hydrophobic block polymerization enhanced the strength of the hydrogel.Then we proceeded to the self-healing experiment using a suitable gel and found that the hydrogel has good self-healing properties and can be extruded through a common medical syringe.Next,we studied the photo-responsiveness of the hydrogel using ultraviolet light.After a period of UV illumination,the hydrogel undergoes a gel-sol transition.Through spectral analysis,we found the photolabile o-nitribenzyl ester group is cleaved under UV irradiation.As a result,the hydrophobic domains formed by o-nitrobenzyl ester bond were ruptured,thereby degrading the hydrogel.Finally,we used the photo-degradation hydrogel to measure the delivery of the anticancer drug doxorubicin.We found that the light can control the release of doxorubicin and effectively increase the mortality of cancer cells.2.The diseased tissue contains a high concentration of reactive oxygen species(ROS).A ROS responsive self-healing polypeptide hydrogel can be prepared by the principle of oxidation from hydrophobic thioether bonds of methionine to hydrophilic sulfoxides and sulfones under hydrogen peroxide stimuli.Firstly,methionine is prepared into an active monomer,and then a four-arm polyethylene glycol amino group is used as an initiator to initiate polymerization of the active monomer to obtain a block polypeptide.A hydrophobic cross-linked self-healing hydrogel was prepared by dissolving the polypeptide in water,which can undergo a sol-gel transition under the action of hydrogen peroxide.A variety of instrumental test results show that the polypeptide will be oxidized under the action of hydrogen peroxide,and the change of the fluorescence emission spectrum of Nile Red further confirmed that the oxidation process will cause the hydrophobic domain destroyed.Then we used doxorubicin as model molecule and the release profiles from the hydrogels with or without the presence of H2O2 were studied.The result suggested that hydrogen peroxide caused an accelerated rate of doxorubicin release in the hydrogel.Finally,cell viability experiments showed that co-culture of doxorubicin-loaded hydrogels with cancer cells resulted in a decrease in the survival rate of cancer cells,indicating that the hydrogen peroxide-responsive hydrogel has potential applications in physiologically pathological tissues.3.Using four-arm polyethylene glycol amino group as an initiator to initiate polymerization of photo-degradable y-o-nitrobenzyl-L-glutamate monomer and hydrogen peroxide responsive methionine monomer to obtain a dual responsive polypeptide hydrogel.The dual-response polypeptide hydrogel degraded under combination in vivo stimulation and in vitro stimulation,which can effectively avoid side effects caused by single stimulation and improve the accuracy of targeted release.The hydrophobic domains composed of o-nitrobenzyl ester and thioether bonds impart self-healing properties to the hydrogel.When only a single stimulus acts on the hydrogel,the strength of the hydrogel will decrease but will not completely degrade,and the hydrogel will degrade only combination the ultraviolet light and hydrogen peroxide.The response process was analyzed by a variety of instruments.The release of model drug doxorubicin under dual response further verified its dual response properties.