Beyond drug-eluting stents


Currently available bare metal coronary and peripheral stents are prone to thrombosis and restenosis. Drug-eluting stents have great potential in reducing these problems, but what happens when the drug is gone? Stent design, surface character and purity/homogeneity improvements still need to be improved.

The first successful human trials on drug-eluting stents are out now claiming a significant reduction of restenosis in general and in-stent restenosis in particular. The basic principle of drug elution from stent surfaces to prevent or reduce in-stent restenosis appears to be fairly simple: by cell cycle inhibition or direct cellular toxicity targeting at smooth muscle proliferation it is hoped to achieve beneficial effects on the growth pattern of the “neo-intima. But does it really do what it is supposed to do. A huge number of questions remain unanswered:

  • How do endothelial cells deal with cell inhibition?

  • How well is the matrix component tolerated into which the drug is embedded?

  • How homologous is the coating?

  • Are there critical nude stent areas prone to galvanic or other corrosion mechanisms?

  • Furthermore, do the trials in which drug elution proves to be superior really reflect true clinical daily practice?

  • It may be that by the time that drug-eluting stents can truly prove their worth, the focus may already have turned towards stents with advance technology coatings. At the moment much emphasis is put on killing or growth inhibition of vascular wall cells, how long until research on the design of biologically competent and endothelial cell friendly surfaces take centre stage?

    At the 15th International Symposium on Endovascular Therapy, Goetz Richter of Heidelberg, Germany, said: “In our lab we have investigated a nanofilm technology platform based on PolyphosphazeneF, which showed reliable prevention both of early stent thrombosis and late restenosis in various animal models (rabbit iliac arteries, mini-pig renal and iliac arteries) applying various stent design and materials. Others have found ultra-thin ceramic coating also very effective.

    “Before all and everything is being concentrated on the quest for the right drug,”warned Richter, “a little more attention should be paid to improving stent designs, its metallic components and its thrombogencity by biologically effective nanocoatings, before we consider if drug coating is really necessary.

    Continuing on the theme of potential alternatives to drug-eluting stents, Michael Kutryk of St. Michael’s Hospital in Toronto gave a presentation entitled “The future beyond drug-eluting stents: accelerated endothelialization of ePTFE vascular conduits by endothelial progentior cell capture.

    He explained how new technology allows endothelial cell seeding of arterial stents, using immobilised antibodies to circulating endothelial progenitor cells, bound to the metal surface.

    Kutryk said that Dextran and gelatin coated expandable polytetrafluoroethylene (ePTFE) grafts were functionalised with mouse anti-human CD34 antibody (with Propidium Iodide used as a nuclear marker). CD34 antibody-coated R-stents were implanted into the coronary arteries of juvenile Yorkshire swine with a stent to artery ratio of 1.1:1. Animals were sacrificed after 1, 4, and 24 hours and at 28 days. The stented segments were examined histological, immunohistochemically and by scanning electron microscope. The findings of this study were that Dextran and gelatin coatings containing antibodies directed against endothelial progenitor cell surface antigens are capable of attracting and binding these cells both in vitro and in vivo. This is the first demonstration of a method for the rapid reconstitution of a functional endothelial cell monolayer on a stented arterial surface

    Kutryk explained that the pig cells created a blood vessel “skin”that adhered to the stainless steel scaffolding. When endothelial cells touch one another, they stop growing and that creates a monolayer of cells that doesn’t proliferate and invade the stent. Kutryk said his studies have shown the stem cells cover the stents within 48 hours of deployment. He also said the studies showed the coated stents are biocompatible and that the antibody layer is successful in recruiting the endothelial progenitor cells.

    Orbus Medical Technologies will sponsor human trials of the stents in about six months. The trials will probably be conducted first in Europe because the bare stainless steel stent being used as the base for the coatings is