Effect Of A Novel Stent On Re-Endothelialization, Platelet Adhesion And Neointimal Formation

Part I:Fabrication of VE-cadherin Eluting Zwitterionic Stent and Its Effect on Re-Endothelialization and Platelet Adhesion In VitroPurpose:To fabricate VE-cadherin eluting zwitterionic stent (VE-cad-Z stent) and evaluate its ability to resist platelet adhesion and capture outgrowth endothelial cells.Methods:PEG-MPC zwitterionic polymers were anchored onto the exterior surface of BMS by ATRP functionalities, and anti-VE-cadherin antibodies were covalently coated on it to produce VE-cad-Z stents. Then, VE-cad-Z stents were examined by platelet adhesion test, platelet activation test and outgrowth endothelial cells capture ability test in vitro.Results:In vitro, VE-cad-Z stents showed better platelet-resistance, there was almost no platelet adhered on VE-cad-Z stents, while a great number of platelets adhered on bare metal stents (BMS). The platelet activation of BMS was 13.7%, while the platelet activation of VE-cad-Z stents was only0.05%. And VE-cad-Z stents captured significantly more OECs than BMS (75.23±5.71 cells/field versus 17.49±4.26 cells/field, P<0.01).Conclusion:VE-cad-Z stents showed excellent abilities to resist thrombus and to capture OECs.Part II:Effect of VE-cadherin Eluting Zwitterionic Stent on Re-Endothelialization, Platelet Adhesion and Neointimal Formation In VivoPurpose:To exam the safety and efficacy of VE-cadherin eluting zwitterionic stent (VE-cad-Z stent) in a rabbit carotid model.Methods:Fifteen bare metal stents (BMS) and fifteen VE-cad-Z stents were implanted into rabbit carotid arteries. All stents were examined by Doppler ultrasound every 3 days after implantation. Arterial angiographies were performed confirm the position and patency rate of the stents before harvest (3 days or 30 days after implatation). The harvested arteries with stents were divided into four segments for H&E, scanning electron microscopy (SEM), immunofluorescent staining and western blot.Results:Three BMSs were observed with thrombotic occlusion within 3 days by arterial Doppler ultrasound, while all the rest stents maintained patency until they were harvest. In vivo, VE-cad-Z stents showed significantly reduced platelet adhesion and neointima formation (neointima area:1.13±0.05 versus 1.00±0.05 mm2, P< 0.01, and 3.04±0.11 versus 1.05±0.06 mm2, P< 0.01,3 days and 30 days respectively,% stenosis:20.99±0.98 versus 18.72±0.97, P< 0.01, and 56.46±2.20 versus 19.45±1.24, P< 0.01,3 days and 30 days respectively). And 30 days after implantation, the expression of a-SM Actin and MCP-1 in VE-cad-Z stents was significantly lower compared with the BMS (a-SM Actin:0.51±0.09 versus 1.50±0.15, MCP-1:0.14±0.05 versus 2.30±0.23), and eNOS protein expressed in the VE-cad-Z stents was significantly higher than in the BMS (0.49±0.08 versus 0.09±0.02).Conclusion:VE-cad-Z stents showed excellent abilities to resist thrombus and to capture outgrowth endothelial cells, and thus reduced inflammatory response and neointimal hyperplasia after implantation.