A Soft, Conductive External Stent Inhibits Intimal Hyperplasia in Vein Grafts by Electroporation and Mechanical Restriction

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.