The Use of Microfabricated Probes to Penetrate the Internal Elastic Lamina and Intimal Hyperplasia

Abstract

The local administration of drug or gene therapy to inhibit restenosis is currently limited by the internal elastic lamina and atherosclerotic plaque. Microprobes fabricated with micro electrical mechanical systems (MEMS) technology offers the potential for effective delivery of high concentrations of therapeutics through these barriers. However, excessive trauma in penetrating these barriers will enhance restenosis. Accordingly, we examined the importance of microprobe tip sharpness versus height in transecting the IEL and hyperplastic intima. Three groups of microprobes were examined: 65 ± 15 and 140 ± 20 μm tall sharp, and 185 ± 25 μm tall blunt microprobes. Data was collected from 94 microprobes in normal and 46 microprobes in atherosclerotic rabbit iliac arteries. In normal vessels, the 140 ± 20 μm sharp microprobes all transected the IEL and did so by maintaining the transected edges adjacent to the microprobe tip minimizing vascular damage. Few 185 ± 25 μm blunt microprobes transfected the IEL, but when they did, the edges were snapped well beyond the microprobe tip. All microprobes compressed the hyperplastic intima, but were not tall enough to gain entrance to the media. A novel approach to penetrate the barriers to delivery of drug and gene therapy utilizing MEMS technology is presented. Microprobe tip sharpness and associated radial stress application are more important than height. Future microprobes will have to be taller to reach the media in arteries with atherosclerosis.