| Summary: | 博士 === 中原大學 === 生物醫學工程研究所 === 106 === Angioplasty is considered the most effective treatment for atherosclerosis. The stent currently used in clinical medicine is divided into a typical vascular stents and an drug-coated stents. Use of typical vascular stents has a high probability of restenosis development. Vascular restenosis occurs within a few months after stent implantation, and patients require surgical intervention. In contrast to such stents, drug-coated stents can effectively inhibit the growth of vascular endothelial tissues on stents. Given the physiological mechanism, drug-coating inhibits tissue growth on the stent, induces the local regulation of tissue inflammation, and triggers an immune response. However, the efficacy of such stents is limited because the metabolites in the blood of the human body rapidly metabolize the drug on the stent.
In this study, we developed and examined a stent drug-release system that overcomes the problems in current stent technology. In addition, we designed the drug storage stent. The stent can be used to achieve long-term controlled drug release and to treat cardiovascular-related diseases. Rapid production of brackets through mold forming.
The study used a "toggle-type micro-tooling machine" for micro-engraving of the mold, and injected polycaprolactone (PCL) into the designed mold to produce a stent having a length of 28 mm and a diameter of 6 mm. Micropores with a diameter of 0.5 mm and a depth of 0.6 mm were created on the stent. The stent has 54 holes, each of which can store 0.12 c3 of drug. In order to determine the optimal PCL concentration material for the stent, three stents with PCL concentrations (20%, 25%, and 30%) composite material were prepared in the experiment.
The AFM results showed that the PCL 25% composite material concentration of the stent had the smallest surface roughness (RA = 1.77E + 02nm) and had the lowest effect on the blood vessels. In the sample with the PCL 25% composite material concentration, the stent surface was smooth and without fractures under 25× magnification , while under 500× magnification, an even surface was observed . In addition, With an increase in PCL composite material concentration from the PCL 20% to 30%, the load increased from 39.718 to 63.5 N. Young’s modulus increased from 31.44±4.1MPa to 33.10±2.7 Mpa. In addition, four proportions of PCL:PLGA (10:0, 8:2, 5:5, 0:10) were tested. After degradation experiments, it was found that when the proportion of PCL of the mixture increased, the PBS exudation rate slowed down. Verify that the molecular weight is changed to control the rate of degradation. The corresponding pore degradation time was employed as a reference parameter for controlling the amount of drug release in the stent design.
The results indicated that the hemolysis of vascular stent material was 1.2%. The results of this study indicated no hemolysis, which verified that the biodegradable drug-loaded vascular stent was suitable for application in the bloodstream. The result of Platelet experiment which revealed that surface roughness affected the amount of platelet and fibrinogen adhesion. And less roughness on a stent surface reduced platelet adhesion and blood coagulation. The results of drug release rate showed that the release of everolimus increased with time, and the release amount was the highest at 8 hours, and the release rate was 36.95%.
The result of coverage experiments have shown that hyaluronic acid coated everolimus is slowly elevated, and everolimus is slowly infiltrated into hyaluronic acid. This result of the swelling rate experiment, it was found that the degree of swelling containing everolimus was 13 times lower than that of the original hyaluronic acid. Therefore, hyaluronic acid encapsulates everolimus, which does would not block blood vessels. After 120 h, the amount of LDH release did not show any evident increase (p < 0.05). The release rate of LDH in this study was 13–18%, which indicated that the cocultivation of vascular stent material and cells did not cause high levels of cell death or damage, biocompatibility was high, and it was suitable for use in blood vessels.
The result of animal experiment was carried out by pig (Lanyu 200), aged from 6~7 month, male and weighed about 50 kg. To verify the biocompatibility between the scaffold and the animal, the results showed that it was initially observed in the animal for 3 months. The material was high compatibility in the blood vessels of the pigs, and there was no toxicity, no rejection, no effect Animal life. The "bioabsorbable composite stent " developed in this study is proved to be suitable for application in blood vessels.
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