State Key Laboratory of Natural and Biomimetic Drugs and Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, People's Republic of China.
J Mater Sci Mater Med. 2013 Nov;24(11):2601-9. doi: 10.1007/s10856-013-5009-z. Epub 2013 Aug 23.
Drug-eluting stents have shown an impressive reduction of in-stent restenosis for many years. However, stent thrombosis due to incomplete/late endothelialization has raised major safety concerns. To overcome these problems, we developed for the first time a polymer-free sirolimus-eluting antibody-coated stent (PFSEACS) by combining polymer free and endothelial progenitor cell-capture pro-healing approaches. In the first phase, the stents were prepared by loading sirolimus on the porous outer stent surface and directly fixing the anti-CD34 antibodies without any medium carriers on the blood contacting surface. The dose and elution of sirolimus, the amount and stability of anti-CD34 antibody immobilization, and the rate of CD34+ cell capture were evaluated. In the second phase, the stents were validated in an animal model of coronary arteries in pigs. The stent was observed to start collecting endothelial progenitor cells ~2 h after stent implantation and exhibited greatly enhanced endothelialization while maintaining an excellent anti-restenosis activity comparable to the polymer-free sirolimus-eluting stents. Overall, both in vitro and in vivo evaluations indicated that novel PFSEACSs exhibited facilitated endothelialization with excellent anti-restenosis activity and thus should merit further clinical studies.
多年来，载药支架在减少支架内再狭窄方面表现出了令人瞩目的效果。然而，由于不完全/晚期内皮化导致的支架内血栓形成引起了重大的安全问题。为了克服这些问题，我们首次通过结合无聚合物和内皮祖细胞捕获促愈合方法，开发了一种无聚合物的西罗莫司洗脱抗体涂层支架（PFSEACS）。在第一阶段，通过将西罗莫司加载到多孔外支架表面，并直接将抗 CD34 抗体固定在与血液接触的表面上，而无需任何介质载体，从而制备支架。评估了西罗莫司的剂量和洗脱、抗 CD34 抗体固定的数量和稳定性以及 CD34+细胞捕获的速度。在第二阶段，在猪的冠状动脉动物模型中对支架进行了验证。支架在植入后约 2 小时开始收集内皮祖细胞，并表现出大大增强的内皮化，同时保持与无聚合物西罗莫司洗脱支架相当的优异抗再狭窄活性。总体而言，体外和体内评估均表明，新型 PFSEACS 表现出促进内皮化的优异抗再狭窄活性，因此值得进一步的临床研究。
