Making Sense of Stents
|
|
Metal stents with drug-eluting polymer coatings are advanced devices for treatment of reduced coronary artery blood flow, with hundreds of thousands implanted each year in the United States. Recent clinical reports suggest that improved coronary artery patency obtained with these devices may not reduce, and in relatively complicated cases, may increase late (> 6 month post-implant) thrombosis and myocardial infarction. Current theories as to why this occurs will be summarized, and the rationale for a bioresorbable stent (one that dissolves over time) will be presented. Our laboratory developed a bioresorbable stent, deployable by standard intracoronary balloon angioplasty techniques, that allows coronary artery wall mechanical support, plus drug delivery. The helical coil design is based on the limaçon of Pascal. Fabricated with 100 μm diameter bioresorbable poly-(L-lactic acid) fibers (PLLA), the 1.5 mm diameter furled stent expands, at 3 atm, to a 3.0 mm helix. A high strength-to weight ratio allows high buckling resistance (140-210 kPa), depending upon fiber ply and coil spacing. Stent strength is enhanced by a localized torsional set of the fibers as the internal coils expand: in situ thermal annealing treatment (performed with some other bioresorbable stent designs) is unnecessary. The stent is expected to be fully degraded to CO2 and water within two years following implantation. Preliminary results of 28-day implants in pig coronary arteries have been promising. Anti-inflammatory agents (curcumin, paclitaxel) have been loaded into PLLA fibers by melt extrusion. A tradeoff exists between fiber strength and drug capacity. Curcumin loading at 10wt% reduces individual fiber strength but does not induce stent collapse. Uniform curcumin elution from PLLA fibers continues for > 1 month. Eluted curcumin retains significant bioactivity as measured by reductions in pre-activated neutrophil and macrophage adhesion to curcuminated PLLA fibers, and residual cellular activity. Inflammation, observed near drug-free PLLA stent fibers in early implant studies, has been reduced by improvements in polymer purity and fabrication quality. Long-term animal implantations of drug-loaded PLLA stents are scheduled to begin shortly, in order to assess improvements in the inflammatory response. Multiple-ply fiber designs, and foamed polymer coatings permit polymer blends and multiple drug loadings to be used in advanced designs. |
|
MetroCon 2007 |
|
“Innovating for Society” |
|
Biotechnologies |
|
Dr. Eberhart is Adjunct Professor of Surgery at UT Southwestern and Professor of Bioengineering at UT Arlington. He received the AB from Harvard College in 1958 and the Ph.D. (ME) from UC Berkeley in 1965. After graduation from Cal he joined the Institute of Medical Sciences in San Francisco where he was involved in the development and evaluation of the first computer-based patient monitoring system, and also, an early membrane oxygenator design, successfully applied to support the human lung in acute respiratory failure. Following one year on the ME faculty at UT Austin, Dr. Eberhart became Professor of Engineering in Surgery at UT Southwestern, where he has been involved in research and teaching for the past 30 years. His life-long goal was to establish a firm basis for engineering training in the new discipline of bioengineering. In 1984, Dr. Eberhart became the first Director of the Joint UT Southwestern-UT Arlington Graduate Program in Biomedical Engineering, serving for 18 years. In 1976 Dr. Eberhart began a series of studies to evaluate the physiological and biological responses to artificial organ support of the heart and lungs. This led to improved methods for combined mechanical and pharmacological support of the failing heart, and to improved biomaterials for artificial hearts, lungs and blood vessels. Dr. Eberhart also conducted studies of heat transfer and temperature regulation, and co-edited a two-volume book Heat Transfer in Medicine and Biology. Dr. Eberhart began studies of methods to improve the performance of stents in 1993, inventing a biodegradable stent for the delivery of drugs and gene therapy for treatment of coronary arterial disease, cancer, etc. He formed a company, Texas Stent Technologies, Inc., to exploit these findings. He has published over 150 technical papers, edited two books and has two patents. Dr. Eberhart served for ten years on the Board of Directors of Advanced Neuromodulation Systems, Inc., a company that develops spinal chord and deep brain stimulation systems. Dr. Eberhart has held several national offices of professional organizations, including President of the American Society for Artificial Internal Organs. He is an ASME Fellow, a Founding Fellow of the American Institute for Medical and Biological Engineering, and an Inaugural Fellow of the Biomedical Engineering Society. |
|
About the Speaker: |
