| Part ⅠThe development of bio-corrodible nitrided iron stent applied to large arteryObjectiveIndependently develop the bio-corrodible nitrided iron stent, and through in vitro experiments to test the mechanical characterization, corrodible properties and blood compatibility of the bio-corrodible nitrided iron stent. Explore the feasibility of self-developed bio-corrodible stent.MethodsUsing the pure iron tubes as the raw material to develop the bio-corrodible nitrided iron stent,which by process of drawing iron tubes repeatedly,laser engraving,degreasing,pickling technology,electrochemically polishing, and using surface passivation and vacuum plasma nitriding technique.The tensile strength(TS),radial strength(RS), stent stiffness(SS) and electrochemical corrosion rate were evaluated in vitro.In the nitrided iron stents,the mechanical characterization,corrodible properties and blood compatibility were compared with those of the control pure iron and 316L stainless steel stent.At the same time,to test the blood compatibility index through in vitro experiment, including platelet adhesion test, hemolysis rate(HR) test, prothrombin time(PT) and activated partial thromboplastin time(APTT), and compared with the control 316L stainless steel.ResultsSuccessfully developed pure iron stent after a series of processes,and the bio-corrodible nitrided iron stent was developed using a vacuum plasma nitriding technique.1 The results of the mechanical characterization and corrosion rate in vitroThe mechanical characterization of bio-corrodible nitrided iron stent:TS (MPa):603.28 16.26,RS (kPa):93.62 ± 5.44,SS (kN/m):5.82 ± 1.87,There were significantly increased compared with the control pure iron stent (TS (MPa):337.76 ± 3.17,RS (kPa):57.51 ± 4.44,SS (kN/m):35.13 ± 3.90), P<0.05).But there weren’t significantly increased compared with the control 316L Stainless steel stent (TS (MPa):614.37 ± 6.82,RS (kPa):96.55±7.75,SS (kN/m):58.59 ± 3.93),P<0.05).The corrosion rate of bio-corrodible nitrided iron stent in vitro were significantly increased compared with the control pure iron stent,0.191±0.018 mm year-1 vs 0.100±0.035 mm year-1,P<0.05.2 The results of blood compatibility in vitroPlatelet adhesion test showed that the platelet adhesion of bio-corrodible nitrided iron stent weren’t significantly difference compared with the control 316L stainless steel stent,P> 0.05.The platelet adhesion of bio-corrodible nitrided iron stent (piece):30min,35±6;60min,83±14,and the platelet adhesion of 316L stainless steel stent (piece):30min:40±10,60min:79±15. The HR of bio-corrodible nitrided iron stent was 3.1%,it was less than the safety value of 5%. PT and APTT of bio-corrodible nitrided iron stent:PT(s),13.53±0.45, APTT(s) 33.37±0.64.PT and APTT of 316L stainless steel stent:PT(s),12.65±0.79,APTT(s) 30.43±1.56.PT and APTT weren’t significantly difference between bio-corrodible nitrided iron stent and 316L stainless steel stent, P>0.05.ConclusionsThe mechanical characterization of pure iron stent were enhanced through using a vacuum plasma nitriding technique,and weren’t significantly difference compared with the control 316L stainless steel stent. The corrosion rate of bio-corrodible nitrided iron stent was faster than the pure iron stent in vitro. In addition,the blood compatibility of bio-corrodible nitrided iron stent also weren’t significantly difference compared with the control 316L stainless steel stent. In vitro physical and chemical experiments fully confirmed that the quality of bio-corrodible nitrided iron stent by self-developed meet the design requirements,and also meet the conditions for further animal experiments.Part Ⅱ The Animal experiments of nitrided iron stent applied to large artery in healthy juvenile mini-swine iliac arteries modelObjectiveThe biodegradability and biocompatibility of bio-corrodible nitrided iron stent applied to large artery were investigated in healthy juvenile mini-swine iliac arteries models, and compared with 316L stainless steel stent. Preliminary explore the biodegradability and biocompatibility of bio-corrodible nitrided iron stent in vivo. Providing a theoretical basis for bio-corrodible nitrided iron stent applied to Clinical application.MethodsTwenty healthy juvenile mini-swine were divided into four groups randomly and equally in our experiment in which without consideration gender differences. Every juvenile mini-swine was underwent fluoroscopically guided placement of stents and were divided into four groups using a randomized block design method:1-month group,6-month group,12-month group and 24-month group. Twenty experimental swines with 20 nitrided iron stents were implanted into left iliac arteries, and 316L stainless steel stent implanted into the right iliac arteries respectively after stent insertion. Digital subtraction angiography (DSA) images of iliac arteries and the plasma iron concentration of all swines were evaluated 1,6,12 and 24 months (30,180,360 and 720 days) respectively after stent insertion. Then, the animals were sacrificed. Meanwhile, the segment of the artery with stent was removed and underwent HE staining in every swine. The remaining strut thickness and surface area coverage of the nitrided iron corrosion product at different implantation periods were observed by biomedical image analysis software, in order to estimate stents degradation time.The plasma iron concentration, intimal thickness, luminal diameter and inflammation scoring of nitrided iron stents and 316L stainless steel stent were observed at different implantation periods.ResultsAll of the experimental stents were successfully implanted into the iliac arteries of the juvenile pigs. Operation success rate was 100%.All pigs undergoing stent implantation survived the procedure, were healthy and growing, and no iron poisoning were observed. Scanning electron microscopy image revealed that a nearly intact layer of endothelial cells formed on the nitrided iron stent-implanted vessel wall an 1 month after the procedure. Parts of stent struts began to be degraded. But the stent form integrated were observed after 6months, and that most stent struts were fractured and began to be corroded after 12 months, and that stents kept corroded with partial residue after 24 months and outer end luminal diameter stenosis were observed by digital subtraction angiography images only. Follow-up angiography during and after implantation showed no trace of in-stent thrombosis, distal branch embolism,vascular rupture, ulceration,stent displacement, or any other complications. No adventitial hemorrhage, aneurism, or other abnormality was found when the stented segments were checked.1 In vivo degradation of bio-corrodible nitrided iron stent applied to large arteryStrut thickness of the nitrided iron stents thinning gradually at different implantation periods:1 months 116.83±8.61μm,6 months 101.63±11.81μm,12 months 86.87±8.42μm, and 24 months 41.24±6.48μm, there were significant difference at different implantation periods,P<0.05. Surface area coverage of the nitrided iron corrosion product increasing gradually at different implantation periods: 1 months 32308.68±238.14μm2,6 months 109948.66±519.42μm2,12 months 159563.12±688.13μm2 and 24 months 318453.99±577.52μm2, there were significant difference at different implantation periods,P<0.05. By means of linear regression analysis estimate the eorrosion period of nitrided iron stents in pigs which was 1118.35 days.2 Biocompatibility of bio-corrodible nitrided iron stent applied to large arteryIntimal thickness of the nitrided iron stented segments at different implantation periods:1 months 0.13±0.02mm,6 months 0.43±0.02mm,12 months 0.45±0.03mm and 24 months 0.48±0.10mm,and 316L stainless steel stented segments:1 months 0.15±0.04mm,6 months 0.51±0.02mm,12 months 0.53±0.10mm and 24 months 0.57±0.13mm, there weren’t significantly difference at nitride iron stented segments compared with the control 316L stainless steel stented, P>0.05. In-stent luminal diameter of the nitrided iron stented segments at different implantation periods:1 months 7.82±0.25mm,6 months 7.44±0.50mm,12 months 7.35±0.38mm and 24 months 7.30±0.38mm, and 316L stainless steel stented segments:lmonths 7.86±0.25mm,6 months 7.35±0.17mm,12 months 7.04±0.19mm and 24 months 6.67±0.03mm, also didn’t significantly difference at two stented segments, P>0.05. There weren’t significantly difference of inflammation scoring at nitride iron stented segments compared with the control 316L stainless steel stented, P> 0.05.The plasma iron concentration of all swines:preoperative 1.31±0.37mg/L(n=20),1 months 1.32±0.10 mg/L(n=5),6 months 1.34±0.12 mg/L(n=5),12 months 1.43±0.19 mg/L(n=5) and 24 months 1.39±0.16 mg/L(n=5), there weren’t significantly difference at different implantation periods that analyzed by the one-way analysis of variance, P> 0.05.ConclusionsOperation success rate is high that stent implanted into the iliac arteries of the juvenile pigs.It was observed that the biodegradability of bio-corrodible nitrided iron stent applied to large artery is well in vivo. There weren’t significantly difference of biocompatibility at nitride iron stented compared with the control 316L stainless steel stented. Iron ions produced in the process of nitride iron stent degradation did’t affect the plasma concentration of iron ions in vivo. Preliminary findings suggested nitride iron stent is safe and feasible, It’s worthy of further study. |
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