Preparation And Biocompatibility Study Of Redox Responsive C-HA-Cys-Allicin Hydrogel Coating

In recent years,cardiovascular disease has become the most harmful disease in the world.Atherosclerosis could lead to cardiovascular diseases such as coronary heart disease and cerebral infarction.Their pathology is closely related to inflammation and oxidative stress.At present,interventional therapy is a common method for treating atherosclerosis.Traditional drug-eluting stents application can cause advanced thrombosis,intimal hyperplasia,and stent restenosis,due to poor biocompatibility,lack of personalized treatment and late toxic side effects.In order to solve these problems,this study constructed a hydrogel coating with redox response capability,which can regulate the drugs release to aim at the inflammation and oxidative stress environment in the atherosclerotic lesion area.Loaded the endogenous drug allicin on the coating to regulate the process of vascular remodeling after the interventional treatment,thereby inhibiting the occurrence of restenosis in the stent.Firstly,hyaluronic acid was modified by catechol group,then crosslinked with cysteamine（Cys）to synthesize the C-HA-Cys hydrogel.The optimal feeding ratio C-HA:EDC:NHS:Cys=1:3:3:6 was selected by observing the surface morphology,roughness and sulfur content of the hydrogel coatings with different feeding ratios.This feeding method was stability and smooth.The hydrogel coating was placed in hydrogen peroxide solution to prove that the hydrogel coating could be oxidized by hydrogen peroxide solution and had redox response.Secondly,the C-HA-Cys-Allicin hydrogel coating was prepared by loading different concentrations of allicin in the C-HA-Cys hydrogel.The drug coatings with different were analyzed and characterized,and it was found that when the drug concentration was 5 g/m L,the surface of the coating was smoother,the roughness was the lowest and the sulfur content was the highest.The coating of hydrogel loaded with rhodamine was placed in PBS solution,GSH solution and H₂O₂ solution respectively,and it was found that the coating could release drugs in redox environment.Next,the antibacterial properties and blood compatibility of different concentrations of C-HA-Cys-Allicin hydrogel coating were explored.It was found that the drug-loaded coating had significant inhibitory effect on the growth of staphylococcus aureus,and the inhibitory effect was increased with the increasing of drug concentration.Also,the drug loading coating had good blood compatibility,especially when the drug concentration is 5g/m L.Finally,the cell compatibility of different concentrations of C-HA-Cys-Allicin hydrogel coating was investigated.It was found that the drug-loaded coating could repair endothelial cells after ox-LDL injury and inhibit the proliferation of macrophages and smooth muscle cells.The histocompatibility of C-HA-Cys-Allicin hydrogel coating with different concentrations was tested,it was found that the sample prepared with 5 g/m L Allicin had the smallest newborn cyst tissue and newborn intima area.In this study,the redox-responsive C-HA-Cys-Allicin hydrogel coating can be manufactured on the surface of vascular interventional devices to achieve precise response to the environment of the diseased area with inflammation and oxidative stress,which can attain the purpose of prevention in-stent restenosis and ensure the effectiveness and safety of the application of interventional devices.