Song Chun-Li,Li Qian,Yu Yun-Peng,Wang Guan,Wang Jin-Peng,Lu Yang,Zhang Ji-Chang,Diao Hong-Ying,Liu Jian-Gen,Liu Yi-Hang,Liu Jia,Li Ying,Cai Dan,Liu Bin
Introduction: Intravascular coronary stenting has been used in the treatment of coronary artery disease (CAD), with a major limitation of in-stent restenosis (ISR). The 316 stainless steel has been widely used for coronary stents. In this study, we developed a novel coating method to reduce ISR by simultaneously coating vascular endothelial growth factor (VEGF) and anti-CD34 antibody on 316L stainless steel. Methods: Round 316L stainless steel sheets in the D-H group were polymerized with compounds generated from condensation reaction of dopamine and heparin using N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide (EDC) and N-hydroxysuccinimide (NHS). Sixteen sheets from the D-H group were further immersed into 1ug/ml VEGF165 and 3mg/ml heparin sodium one after another for 10 times, and named as the D-(H-V)10 group. Eight sheets from the D-(H-V)10 group were coated with anti-CD34 antibody and termed as the D-(H-V)10-A group. Immunofluorescence assay and ELISA were used to evaluate whether the 316L stainless steel disks were successfully coated with VEGF and anti-CD34 antibody. Results: The results of immunofluorescence assay and ELISA showed that VEGF could be detected in the D-(H-V)10 and D-(H-V)10-A group, suggesting the steel sheets were successfully covered with VEGF. Anti-CD34 antibody could only be observed in the D-(H-V)10-A group, which was the only group coated with CD34 antibody. Both results suggested that the 316L stainless steel sheets were successfully coated with VEGF and anti-CD34 antibody. Conclusion: Our study developed a method to simultaneously coat VEGF and anti-CD34 antibody to stainless metal steel. This research serves as a fundamental role for a novel coating strategy.
Recently, just taking endothelialization of stent as an interventional treatment of aneurysms is unsatisfactory. This treatment also has impacts the occlusion rate of the aneurysm. In accordance with that, the authors aims to construct a novel biological factor-coated stent with dual biological effects of anticoagulation and endothelialization for the improvement of the occlusion rate of aneurysms and reduction of the risk for treatment of aneurysm with intravascular interventional therapy. The Ni-Ti alloy sheets loaded with VEGF and anti-CD34 antibody were put into use for stimulating the construction of the biological factor-coated stents, for the Ni-Ti alloy sheets could help improve the proliferation of endothelial cell (EC), recognize effectively and adhere to endothelial progenitor cell (EPC). Blood compatibility characterization methods (water contact angle, platelet activation test, clotting time evaluation and protein adsorption test) were applied for study the influence of the interaction between the Ni-Ti alloy sheets and blood. Cell experiments (HUVEC proliferation experiment, migration experiment and EPC capture experiment) were resorted to investigate the ability of the sheets to promote the proliferation of HUVEC and to capture EPCs. With the mature of the construction technology, the Enterprise stent with the biological factors were optimized accordingly, the biological function of that were verified by cell experiments. Studies showed that Ni-Ti alloy sheets and enterprise stents can successfully load with VEGF and anti-CD34 antibody. The below achievements can be realized including a better blood compatibility and effects of the constructed sheets and enterprise stents on promoting HUVEC proliferation and adhesion of EPC. It was meaningful of conversion to clinical application to improve the cure rate of the aneurysm and the safety of the intravascular treatment.
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