A Soft, Conductive External Stent Inhibits Intimal Hyperplasia in Vein Grafts by Electroporation and Mechanical Restriction
Li Ding, Hang Chen, Shiyu Cheng, Liujun Jia, Lei Mou, Lixue Tang, Chunliang Zhang, Yangzhouyun Xie, Wenfu Zheng, Yan Zhang, Xingyu Jiang
Abstract
Intimal hyperplasia (IH) in vein grafts (VGs) is a major issue in coronary artery bypass grafting (CABG) surgery. Although external stents can attenuate IH of VGs to some extent, none of the existing external stents have shown satisfactory clinical outcomes. Here we develop a flexible, biodegradable, and conductive external metal-polymer conductor stent (MPCS) that can electroporate the vessel wall and produce a protein that prevents IH. We designed the plasmid DNA encoding the tissue inhibitor of metalloproteinases-3 (TIMP-3) and lyophilized it on the inner surface of the MPCS to deliver into the adventitia and the middle layer of VGs for gene therapy. Coupled with its continuous mechanical support to prevent dilation after implanting, the MPCS can inhibit the IH of VGs significantly in the rabbit model. This proof-of-concept demonstration may aid the development of other implantable bioelectronics for electroporation gene therapy.