Manufacturing Of Iron-based Vascular Scaffold And Study On Its Biodegradation Mechanism

Bioresorbable scaffolds are regarded as the fourth revolution in cardiovascular interventional therapy.As one of the main materials for bioresorbable vascular scaffolds,when compared with polymers and magnesium-based alloys,pure iron has the advantage of being easily modified to greatly increase its strength;its inherent disadvantages are slow corrosion and absorption in the body,the reason and mechanism for slow absorption are not clear yet.Therefore,the main purpose of this research is how to design a Fe-based alloy scaffold with the least amount of iron and the thinnest wall thickness to achieve the mechanical properties equivalent to the permanent stents,and at the same time to have the degradation curve in the body match the healing time of the diseased vascular of the human body,so that it can be completely absorbed as soon as possible after complete degradation.Based on the use of Fe-0.05N alloy,the scaffold design pattern was optimized to achieve an Fe-based vascular scaffold with ultra-thin strut of 50-60 microns,of which the mechanical properties and biocompatibility had been evaluated.In vivo degradation behavior and corrosion products of the iron-based vascular scaffold were investigated both in the rabbit abdominal aorta and porcine coronary artery models,and the bioabsorption mechanism of iron corrosion products was clarified by experiment.Nitriding,which is a traditional surface modification method to introduce non-toxic element N of 0.5wt.%to thin-wall iron tube to get bulk modification effect,combined with the drawing process resulting cold work hardening effect,could significantly increase strength of pure iron,while maintaining the good plastic deformation ability.The scaffold made of Fe-0.05N could make strut as thin as 53 microns,and obtain comprehensive mechanical properties not inferior to the art-of-the-state permanent Co-Cr alloy stents.The IBS sirolimus-eluting iron bioresorbable scaffold with a novel submicron Zn layer intercalation design and the Poly(D,L-lactic acid)(PDLLA)drug-loaded coating,could achieve tunable in vivo corrosion curve by adjusting the amount of Zn and PDLLA.The results showed that the IBS scaffold could keep intact for 2-3 months and then corrode rapidly,but maintain enough support for the blood vessel for 6 months and fully corrode around 2 years,after implantation in the abdominal aorta of rabbits.Saturated extract of iron ions was used to culture L929 cells,and no obvious cytotoxicity was found.Using DMEM+10%fetal bovine serum supplemented with sodium dihydrogen phosphate to extract zinc ions in the IBS scaffold represented a condition closer to the realistic clinical environment.In such case,the original extracts of zinc ions showed no obvious toxicicity to L929 cells.toxicity.Acute thrombogenicity of the bioresorbable scaffolds with permanent stent Xience as control was evaluated ex vivo in a canine carotid arteriovenous shunt model.Zinc was found to have the highest thrombogenicity,and the PDLLA coating can well reduce the high thrombogenicity risk of the Zn layer in the IBS scaffold.Based on the crossing-section area change of the corroded iron strut under optical coherence tomography(OCT),a novel semi-quantitative OCT method to evaluate iron corrosion was established.Compared with the mass losses of iron by the weighing method,results by the OCT semi-quantitative evaluation method had acceptable accuracy,repeatability and reproducibility.Therefore,this method could be used for non-desdructive evaluation of the corrosion of Fe-based bioresorbale scaffolds in human clinical trials.The current work also found that in vivo corrosion and absorption of Fe-based bioresorbable scaffold can be quantitatively evaluated by continuously monitoring the evolution of the artifact size and contrast of the Fe-based bioresorbable scaffold.And the MR imaging evaluation method is non-invasive,which is very suitable for evaluating corrosion and absorption of Fe-based bioresorbable scaffolds during routine clinical use.The corrosion products of the Zn layer in the IBS scaffold were confirmed to include Zn O,Zn₃(PO₄)₂,and Zn CO₃,by energy spectrum scanning and selected area electron diffraction analysis.The corrosion products of Zn layer was demonstrated to be fully bioresorbed after IBS was implanted in the rabbit abdominal aorta for 6-12 months.It is speculated that tissue could metabolize the Zn²⁺to cause movement of the precipitation-dissolution equilibrium of zinc corrosion products towards dissolution until full bioresorption.After the nitrided iron backbone corroded extensively,the corrosion products surrounded in the swelling polylactic acid coating are Fe₃O₄(magnetic,black)and Fe₂O₃.Fe₃(PO₄)₂ and Fe OOH are dispersedly distributed in the tissue outside the polylactic acid coating.The insoluble solid corrosion products of iron in local tissue are mainly engulfed by macrophages to form hemosiderin,which is moved to the adventitia,then the nearby lymphatic system,and finally into the junction of the left subclavian vein and the internal jugular vein through the thoracic catheter,namely back to the normal iron metabolism path in the body to achieve complete absorption by this mechanism.