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Journal of Long-Term Effects of Medical Implants
SJR: 0.332 SNIP: 0.491 CiteScore™: 0.89

ISSN Print: 1050-6934
ISSN Online: 1940-4379

Journal of Long-Term Effects of Medical Implants

DOI: 10.1615/JLongTermEffMedImplants.v10.i12.60
22 pages

Stent-Based Gene Therapy

Marc D. Feldman
Division of Cardiology, University of Texas Health Science Center in San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78284-7872
Bo Sun
Department of Medicine, University of Pittsburgh School of Medicine
Bryan J. Koci
Department of Medicine, University of Pittsburgh School of Medicine
Clarence C. Wu
Department of Medicine, University of Pittsburgh School of Medicine
James Ft. Kneller
Department of Biomedical Engineering, University of Pittsburgh School of Engineering
Harvey S. Borovetz
Department of Biomedical Engineering, University of Pittsburgh School of Engineering
Simon Watkins
Department of Medicine, University of Pittsburgh School of Medicine
Ahmed Nadeem
Department of Biomedical Engineering, University of Pittsburgh School of Engineering
Lee E. Weiss
Department of Electrical and Computer Sciences, Carnegie Mellon University
Michael L. Reed
Department of Electrical and Computer Sciences, University of Virginia
A. J. Conrad Smith
Department of Medicine, University of Pittsburgh School of Medicine
Warren D. Rosenblum
Department of Medicine, University of Pittsburgh School of Medicine

ABSTRACT

Delivery of gene therapy to inhibit intimal hyperplasia has been proposed to prevent postangioplasty restenosis. We sought to apply gene therapy by using a stent-based technique. There are several hurdles that must be overcome before gene-stent therapy can be applied successfully in clinical trials. These include increasing the efficiency of gene delivery through atherosclerotic plaque; increasing intramural retention times; preventing the inflammatory reaction that stents coated with biodegradable polymers can elicit; overcoming the risk of systemic gene delivery; and accessing the adventitia via percutaneous approach. We evaluated a gene-stent delivery mechanism based on microporous metal microneedles developed with nanotechnology in an attempt to overcome some of these problems.
A novel approach to the transfection of genes by microfabricated technology was evaluated in smooth muscle cells in culture. We demonstrated that microneedles can deliver gene therapy to smooth muscle cells in culture and can produce controlled penetration of the IEL and intima. We conclude that taller microneedles need to be developed to reach the media in diseased human arteries and that this technology has the potential to be incorporated in a stent to deliver gene therapy in atherosclerotic plaque.