Preliminary Study On Biological Properties Of Mesoporous Silica-Rapamycin-Heparin Drug Eluting Stent

Part ?:Fabrication and in vitro compability of mesoporous silica-rapamycin-heparin drug-eluting stentPurpose:Fabricating mesoporous silica rapamycin-heparin drug-eluting stent,and then evaluating its effect on the growth of vascular smooth muscle cells and endothelial cells and its biological compatibility in vitro.Methods:Dopamine was used to self-polymerize on the surface of 316L stainless steel stent to form polydopamine layer.The amino group on the surface of polydopamine layer induced the dehydration and condensation of inorganic silicon on the surface of the stainless steel stent through electrostatic force to form a dense and transparent mesoporous silica coating.A mesoporous silica rapamycin-heparin drug-eluting stent(MRHES)was constructed and the bare metal stent(BMS)was observed with a scanning electron microscope.Mesoporous silica-coated stents(MES),mesoporous silica-heparin drug-eluting stents(MHES),mesoporous silica-rapamycin drug-coated stents(MRES),mesoporous silica-The surface condition of rapamycin-heparin drug-eluting stent(MRHES).The surface condition of mesoporous silica rapamycin-heparin drug-auung stent(MRHES)was observed by transmission electron microscopy.Immunofluorescence,platelet adhesion assay and hemolysis test were used to detect the expression of a-actin in rabbit vascular smooth muscle cells,the expression of CD-31 in vascular endothelial cells,platelet adhesion,and blood phase capacitive in rabbits after exposure to BMS,MES,MHS,MRES and MRHES.Results:Mesoporous silica rapamycin-heparin drug-eluting stents were successfully constructed.The mesoporous silica coating does not change the surface morphology of the BMS,and the presence of the drug does not affect the mesoporous structure.MRHES significantly inhibited the proliferation of vascular smooth muscle cells,but inhibited the proliferation of vascular endothelial cells was weaker than MRES.There was no platelet aggregation on the MRHES surface and the haemolysis rate was<5%.Conclusion:Mesoporous silica is a good drug sustained-release coating material.MRHES showed excellent blood compatibility and anti-proliferative capacity on vascular smooth cells,but the ability to inhibit the proliferation of vascular endothelial cells is just better than simply using anti-proliferative drugs.Part II:Mesoporous silica-rapamycin-heparin drug-eluting stent animal experimentPurpose:To test the safety and efficacy of mesoporous silica-rapamycin-heparin drug-eluting stents in a rabbit carotid artery model.Methods:Mesoporous silica-rapamycin-heparin drug-eluting stents(14)were implanted into rabbit carotid artery.The control group was set up to implant bare stents into the rabbit carotid artery(14).B-ultrasound was performed at 30 days and 90 days after operation to observe the patency of the carotid artery stent and record the peak systolic velocity(PSV)of the carotid artery,which was then sacrificed.After being sacrificed,the rabbit carotid artery specimens implanted with the stent were divided into two sections:the first segment was hematoxylin-eosin staining,and the intimal hyperplasia after 30 days and 90 days stent implantation in the rabbit carotid artery was observed;the second segment was scanned by electron microscopy.Observe the endothelialization after 30 days and 90 days stent implantation in rabbit carotid arteries;Results:Twenty eight New Zealand white rabbits did not die during the observation period.The B-ultrasound indicated that 28 stents were unobstructed without displacement or rupture.In the bare metal stent group,PSV showed a slight upward trend during the observation period,but it was not statistically significant.There was no increase in the PSV of MRHES during the observation period.After 30 days,the average thickness of the intima was:BMS:0.14±0.01mm,MRHES:0.08±0.01mm,P<0.01.After 90 days,the average thickness of the intima was:BMS:0.38 ±0.04 mm,MRHES:0.20±0.03 mm,P<0.01.After 30 days,BMS was more endothelialized than MRHES:BMS:92.6±3.1%,MRHES:57.7±7.8%,P=<0.01.After 90 days,the degree of BMS endothelialization was similar to MRHES:BMS:100±0%,MRHES:99.6±0.5%,P=0.06.Conclusion:In the rabbit carotid model,MRHES inhibited intimal hyperplasia early and did not affect endothelialization during the later period.