| BackgroundCoronary artery stent is one of the important advances in the treatment of coronary heart disease.After early bare-metal stent(BMS)implantation,restenosis was present in about 15-30%of patients.This had become a major obstacle in the prognosis of interventional treatment of coronary heart disease.Various approaches,such as uses of different drugs,types of cytokines and intravascular brachytherapy,had been tried,but had not achieved satisfactory results.However,the advent of drug-eluting stents(DES)allowed drugs that intervene in the pathophysiology of restenosis to play a role locally.The drug was released slowly from the coating,inhibiting the proliferation of local smooth muscle cells,and thereby reducing the incidence of restenosis within the scaffold significantly to less than 10%.And the toxic effect of the whole body could be avoided which made a progress in the clinical research results.Compared to bare metal stents,the incidence of late stent thrombosis in drug-eluting stents increased,which may be caused by continued inflammation and allergic reactions in the local area by drug eluting coating.With the improvement of drug eluting stent technology and design,incidence of stent thrombosis was further reduced and had become the mainstream products.In spite of this,in order to avoid permanent stents residues that caused sustainable foreign body inflammation stimulation on blood vessel walls,the development of the biodegradation of stents which could effectively maintain artery vessel patency,release drugs and avoid recoil before the degradation,were one of the development trend in the future.Currently,the main materials used for totally degradable scaffolds are polymers and absorbable metal scaffolds.For polymer degradable scaffolds,the most representative AbsorbTM scaffolds which were made of poly lactic acid(PLA)and the incidence of late adverse events was relatively high,had already announced the exit from the market.This types of Polymer materials are facing more formidable challenges in the future.Now magnesium alloy and iron are the mainly absorbable metal materials.The mechanical properties of magnesium stents are inferior to that of stainless steel and cobalt-chromium alloy.Otherwise,the degradation and absorption speed of magnesium is also fast,and the failure to reach enough supporting window in the early stage might lead to the occurrence of late adverse events.However,iron is stronger and slower resorbable than magnesium alloy,which can effectively prevent early recoil and keep the arteries unobstructed.Some studies have demonstrated that iron biodegradable stents in the porcine coronary artery can maintain safety up to 53 months without adverse cardiovascular events and the scaffolds did not appear too fast degradation in the early days or cause local inflammatory injury to arterial walls.The intimal hyperplasia was not pronounced too.Iron biodegradable stent has achieved initial success,and as for a new type of metal iron DES,there is no research report.ObjectivesBiodegradable scaffolds show many potential benefits over permanent stents in percutaneous coronary intervention.Iron is considered to be one of the most promising bioresorbable materials.In order to develop and study the new type of biodegradable scaffolds in China,here we explore the feasibility,efficacy and safety of Sirolimus-eluting Iron Bioresorbable Coronary Scaffolds(IBSTM scaffolds,Lifetech Scientific Co.Ltd.,Shenzhen,China)in health porcine coronary arteries,compared with contemporary the art of state Cobalt-chromium stent(Xience PrimeTM,Abbott Vascular,Santa Clara,CA,USA)MethodsA total of 56 devices(including 28 IBSTM scaffolds and 28 Xience PrimeTM stents)were randomized implanted in two main coronary arteries including left anterior coronary artery,left circumflex coronary artery and right coronary artery of 28 health nonatherosclerotic swines by using quantitative coronary angiography and optical coherence tomography(OCT)to optimize scaffolds/stents apposition.Each pig had implanted the same brand of stents.Short-term safety and efficacy of the IBSTM scaffolds were compared with Xience PrimeTM stents.OCT and scanning electron microscopy(SEM)were used to explore the endothelial coverage percentage,the growth and healing conditions of endothelial cells,the risks of early stent thrombosis,as well as the inhibitory effect of this novel sirolimus-eluting iron scaffolds on endothelial hyperplasia at 7,14 and 28 days after implantation.Moreover,immunohistochemical analysis was used to test the function of CD31 antibody expression positive endothelial cells.In addition,at 28 days,the two groups of ten animals were executed in order to explore the safety and efficacy of IBSTM scaffolds in short term by means of histopathological analysis,histomorphology analysis and Micro computer tomography(Micro-CT)exam.Values of stented coronary arteries contained neointimal area,luminal area,neointimal thickness,internal elastic area,external elastic area and the percentage of area stenosis were measured The myocardial tissue around stent and the major organs including heart,liver,kidney,spleen,lung were examined for analysis of morphology and toxicology after stenting.Micro-CT was mainly used to detect the corrosion and degradation of the scaffolds.ResultsAll mini-pigs implanted with IBSTM scaffolds and Xience PrimeTM stents survived without any adverse cardiovascular events during the 4 week study.There was no significant difference between the IBSTM scaffolds and Xience PrimeTM stents in neointimal thickness(0.29±0.35 mm vs 0.17±0.17 mm,p=0.325)?neointimal area(1.46±1.37 mm2 vs 1.33±0.80 mm2,p=0.705)?area stenosis(24.05±20.16%vs 22.53±12.04%,p=0.734),vascular injury score(1.45±0.75 vs 0.99±0.57,p=0.141)and inflammatory score(1.24±0.88 vs 1.04±0.83,p=0.607)at 28 days.However,fibrin score of IBSTM was higher than that of Xience PrimeTM stents at 28 days by statistical analysis(1.29±0.72 vs 0.6±0.68,p=0.041).IBSTM scaffolds kept its integral without corrosion after 28 days by the Micro-CT.The endothelialization percent of IBSTM scaffolds were higher than Xience PrimeTM stents in early stage and comparable at 28 days(77±15%vs 30±30%,p=0.032 at 7 days;87±8%vs 64±17%,p=0.017 at 14 days;96±3%vs 96±2%,p=0.861 at 28 days).Meantime,immmohistochemical result showed that the recovery of the endothelial cell physiological functions of IBSTM scaffolds.No abnormal histopathological changes were observed in coronary arteries and main organs.ConclusionsThis study suggested that the IBSTM scaffolds had good blood and tissue compatibility.There was no thrombosis,inflammation,toxicity and necrosis,which was comparable to that of Xience PrimeTM stents in terms of short-term safety and efficacy in porcine coronary arteries.The earlier and complete endothelialization of IBSTM scaffolds indicated its good biocompatibility and probably lower early relevant risk such as stent thrombosis.This preliminary study suggests that the novel Sirolimus-eluting Iron Bioresorbable Coronary Scaffolds is feasible,and further research is worthy. |
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