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Study On The Biocompatibility And Drug Storage Of PEGylated Stereocomplex Polylactide Coating Of Stent

Posted on:2019-02-19Degree:DoctorType:Dissertation
Country:ChinaCandidate:Z B LiFull Text:PDF
GTID:1364330572952959Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Background:Coronary atherosclerotic heart disease has become one of the most serious causes of human health,and the invention of coronary stenting has become the main means of treating coronary heart disease.In cardiac intervention,86% of patients underwent coronary stenting,especially drug-eluting stent implantation.However,during stent application,there are a number of issues that affect patient recovery efficiency and safety,including chronic vascular inflammation and the formation of thrombosis and restenosis.Among them,restenosis is a key factor affecting the effectiveness of stent implantation.Previous studies have confirmed that the occurrence of stent restenosis mainly includes three stages.First,within a few minutes after stent placement,platelets begin to activate,thereby enhancing adhesion and aggregation,while secreting various pro-clotting cytokines,leading to thrombosis.The second stage occurs mostly in the damage repair mechanism after a few days to several weeks after stent implantation.A large number of white blood cells accumulate in the vascular endothelial tearing injury area,and then stimulate the target tissue during the course of the disease.The third stage turns into chronic or permanent inflammation,which usually lasts for several months.Specifically,some smooth muscle cells migrate to the injured area and hyperproliferate,which increases the risk of stent restenosis.In this case,how to avoid thrombosis,reduce the inflammatory response in the stent and inhibit the excessive proliferation of vascular smooth muscle cells are the three main directions to improve the recovery after stenting.Objective:This study aims to develop suitable polymers that have ideal bloodbiocompatibility and can simultaneously carry a variety of drugs(antithrombotic,anti-inflammatory,anti-endothelial cell proliferation,etc.)to improve biocompatibility.Can be loaded with different drugs to improve the risk of stent surgery.Methods:mPEG-PDLA was prepared by mPEG and dextro lactide,purified,and silylated mPEG-PDLA was synthesized by adding 3-isocyanopropyltriethoxysilane,and characterized by proton nuclear magnetic resonance;316 stainless steel sheet surface treatment.A mixed solution of silanized PEG-PDLA was prepared,and the surface-physically adhered mPEG-PDLA was further ultrasonicated with a DMSOwater solution,and finally rinsed with water and dried with nitrogen.(An additional 50 mg/ml of silanized PEG-PDLA and PLLA-PEG-PLLA of the isomeric lactic acid unit were mixed as described above).Four sets of samples were prepared,including SS sheets,PS treated SS sheets(PSSS),mPEG-PDLA modified SS sheets(PEG-PLA-SS),and silanized mPEG-PDLA PLLA-PEG-PLLA modified SS sheets(PEG-scPLA-SS),its physicochemical properties and biological properties were examined.Test: Surface characterization using the contact angle of the modified SS sheet:The hydrophilicity of the modified surface of the SS sheet was measured by the fixed droplets of distilled water.Biocompatibility Testing: Fibrinogen Adhesion Assay: BCA assays and scanning electron microscopy images were used to assess the protein adsorption capacity of modified and unmodified SS sheets.The amount of unabsorbed fibrinogen in the solution was quantified using a BCA protein kit.Finally,the samples were dried overnight in a vacuum and sputtered a thin layer of gold for imaging by SEM.An absorbance microplate reader(Biotek ELX808)was used for quantitative analysis of fibrinogen adsorption capacity.Platelet adhesion and activation of antithrombotic properties before and after surface modification of SS sheets were evaluated by platelet adhesion test.Cell compatibility,quantitative determination of the FLU loading content of the SS sheet to obtain theFLU loading effect.Results:Surface Characterization: The appearance of a formant demonstrates the successful synthesis of mPEG-PDLA and PLLA-PEG-PLLA.Quantification of adsorbed fibrinogen: The PEG-scPLA-SS tablet treated solution showed the highest unabsorbed fibrinogen concentration,up to 40% higher than the concentration treated with the original sample.Quantification of platelet activation and adhesion:The mPEG-scPLA-SS sheet showed a significantly lower level of platelet activation than the modified SS sheet.Drug loading: few fluorescein molecules were observed on the surface of PS-SS and PEG-PLA-SS,while PEG-scPLA-SS tablets showed stronger fluorescein intensity.Cytocompatibility: The surface of PEGscPLA-SS sheet adhered well and proliferated.The number of viable cells increased continuously,which was significantly higher than that of SS treated with PS.Conclusion:The stereo PEGylated polylactic acid is successfully prepared,can be loaded with drugs,and can be successfully grafted onto the surface of the SS sheet to control the hydrophilicity of the surface,significantly improve blood compatibility,and not only can prevent thrombus well,but also It can speed up the repair process and has good biocompatibility.Significance and application value of the Research:In the current study,the surface modification of SS sheets was successfully achieved by PS treatment,silanization and grafting of PEG-scPLA.PS treatment is used to expose more hydroxyl groups on the surface of the SS sheet,and the silanization process provides more effective reaction sites for subsequent polymer grafting.Successful surface modification of PEG-scPLA is responsible for obtaining a stable polymer film on the surface of the SS sheet by forming scPLA.Through systematic analysis of protein adsorption levels,platelet activation rate,drugloading capacity and proliferation ability of various modified surface HUVECs,it can be concluded that PEG-scPLA-modified SS tablets have enhanced biocompatibility,up-regulate DLE,and reduce scaffolds.The best overall performance,such as internal thrombosis,paves the way for the recent treatment of coronary heart disease.The multi-functional scPLA stent with high drug encapsulation capability can be used as a promising platform for a wide range of biomedical applications,including tissue engineering,drug delivery,and antimicrobial therapy.
Keywords/Search Tags:316L stainless steel, silanization, surface graft modification, biocompatibility
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