| Cardiovascular disease has became more and more common because of the development of economy and the diet of people, and threatened people's health seriously. According to statistics, some scholars have anticipated that cardiovascular disease will be the most frequent fatality factor in 2020. Clinically, the use of intravascular stents has gained popularity and becomes an eatablished mode of treatment in percutaneous cardiovascular interventions. However, mural thrombus, elastic recoil and neointimal hyperplasia limit the long-term effectiveness of this treatment. While thrombosis has been controlled with antiplatelet therapy, elastic recoil has been solved with the high radial force of permanent stents, and neointimal hyperplasia has been reduced with the use of drug-eluting stents(paclitaxel and rapamycin). But when the drug is eluted, drug-eluting stents pose problems similar to that of bare metal stents, as permanent foreign bodies in vessel wall which have the risk of continuous interaction between the stent and the surrounding tissue, leading to long-term endothelial dysfunction or chronic inflammatory reaction. These interactions are known as the possible factors for in-stent restenosis(ISS). So how to lessen the mechanical stimulation is one of the hotest points in endovascular stent study. Biodegradable Endovascular Stent(BES) may act as a new biomedical tool which are "fulfilling the mission and stepping away" because of its more physiological repair, reconstitution of local vascular compliance, and a temprory, limited, longitudinal, and radial straightening effect, including the possibility of growth. In 1988, Stack developed the original biodegradable endovascular stent made of poly-lactic acid(PLA). At present, there are three types of BES which are studied most frequently: biodegradable polymers stent, biodegradable iron stent and biodegradable magnesium alloy stent(BMS). Stents made of biodegradable polymers have limited success because of their low radial strength and local inflammation, thus leaving corrodible metals as the best alternatives. BMS's strong radial force, less inflammatory reaction makes it become the most promising biodegradable stent. In earlier studies, biodegradable magnesium alloy stents were proved to be safe and efficient. However, preliminary preclinical and clinical trials had demonstrated that these stents resulted in higher restenosis rates than seen in drug-eluting stents for a modest degree of neointima formation, late recoil and faster degradation. So how to prolong the degradation and lessess the intimal hyperplasia faces reserchers. A new style of BMS called rapamycin-eluting AZ31 biodegradable magnesium alloy stent has been developed by the Institute of Metal Research Chinese Academy of Sciences(Shenyang, China). The stent's surface is electropolished so as to prolong cloting time and decrease thrombosis, also inactivated to lengthen corrosion period. The stent was coated by rapamycin whose carrier is poly (lactic acid-co-trimethylene carbonate) (P(LA-TMC)). The mechanical parameter, blood compatibility, plate adhesion experiment and degradation performance have been completed, and the result is ideal. The purpose of present study was to evaluate the degradation time and the character of inhibiting intimal hyperplasia of rapamycin-eluting AZ31 biodegradable magnesium alloy stent. There have been no reports of drug-eluting magnesium alloy stent all over the world. The study included two parts:Part I:The degradable performance of rapamycin-eluting AZ31 biodegradable magnesium alloy stents in rabit abdominal aorta. Objective:The purpose of this study was to study the degradable performance of rapamycin-eluting AZ31 bioabsorbable magnesium alloy stents in rabbit abdominal aortas. Method:Twenty AZ31 biodegradable magnesium alloystents were deployed in infrarenal abdominal aortas of twelve New Zealand white rabbits. Rabbits were sacrificed in one month (n=5), two months(n=5), three months (n=5) and four months (n=5) after stents implantation. Vessels were harvested, radiographed,and then treated with pathology in order to evaluate degradable performance. Radiography of stented vessel was made to show the whole figure, and the pathology was analyzed by computer in order to anticipate the corrosion time. Results:All animals survived in the scheduled follow-up period. Radiography showed stents were expanded fully in one month, most struts had been already corroded partly in two months and completely in three months, all struts were corroded completely in four months. The corrosion period of AZ31 magnesium alloy stents in rabbit aorta was 105.0 days. Conclusion:Rapamycin-eluting AZ31 bioabsorbable magnesium alloy stents lose radial force in rabbit abdominal aorta in two months, and the corrosion period is 105.0 days.PartⅡ:The study of inhibiting intimal hyperplasia character of rapamycin-eluting AZ31 biodegradable magnesium alloy stent. Objective:The purpose of this study was to evaluate inhibiting intimal hyperplasia character of rapamycin-eluting AZ31 biodegradable magnesium alloy stent in rabbit aortas. Methods:Rapamycin-eluting AZ31 biodegradable magnesium alloy stent (n=22) and AZ31 magnesium alloy stents (n=22) were deployed in aortas of 22 New Zealand white rabbits (2 stents each rabbit). Rabbits were sacrificed in 3 days (n=2),1 month (n=5),2 months (n=5),3 months (n=5) and 4 months (n=5) after stents implantation. Stented vessels were harvested to be made pathology and then calculated with computer. Results:All rabbits survived during follow-up period. No evidence of thrombosis was found in angiography and pathology. Neointimal area in the segment deployed with rapamycin-eluting AZ31 magnesium alloy stent was smaller than that deployed with magnesium alloy stent during follow-up period(1 month:0.60±0.22mm2 vs.1.44±0.04mm2, P<0.05; 2,3,4 months after operation:0.63±0.27mm2 vs.1.41±0.08mm2,0.57±0.14mm2 vs.1.43±0.02mm2,0.58±0.10mm2 vs.1.47±0.03mm2, all P＜0.05). Neointimal thichness in the segment deployed with rapamycin-eluting AZ31 magnesium alloy stent was shorter than that deployed with magnesium alloy stent during follow-up period. The data of two groups are:110.32±65.31μm vs.250.36±114.39μm,91.28±35.31μm vs. 225.12±75.14μm,89.32±38.82μm vs.214.08±75.13μm,116.95±10.44μm vs. 239.37±9.49μm, all P<0.05 in 1,2,3,4 months. So the lumen area was significantly larger in the rapamycin-eluting AZ31 magnesium alloy stents group when compared with AZ31 magnesium alloy stents group. The data of every follow-up time was baned as following:2.44±0.64mm2 vs.1.58±0.43mm2 (1 month),2.64±0.17mm2 vs. 1.93±0.27mm2 (2 months),2.84±0.54mm2 vs.2.04±0.34mm2,(3 months),3.00±0.13mm2vs.2.16±0.08mm2 (4 months), all P<0.05。The endothelialization score of two groups was different obviously in 1 month(1.0±0.21 (experiment group) vs.2.45±0.35(contral group), P<0.05),contrasting with the performance in 2,3,4 months(2.57±0.39 vs.2.25±0.36,2.46±0.11 vs. 2.56±0.39,2.56±0.28 vs.2.38±0.31, all P＜0.05.), which suggested that rapamycin-eluting AZ31 magnesium alloy stents group had delayed endothelialization. There was no obvious difference in internal elastic lamina(IEL) area, injury score, inflammation score between two groups during follow-up period. Conclusion: Rapamycin-eluting AZ31 biodegradable magnesium alloy stent obviously reduces the neointimal hyperplasia and improves the lumen area when compared to AZ31 magnesium alloy stent, but it delays vessel's healing and endothelialization. |
PDF Full Text Request