Feature Article

DESIGN

The development path

Use of stents to treat blocked/restricted coronary arteries has only really been common practice for the past ten years, having replaced coronary artery bypass grafts and percutaneous transluminal coronary angioplasty. Despite this, the market for stents has doubled annually to reach approximately US$5 billion today.

But there have been complications. Although preventing immediate re-closure of the artery wall, bare metal stents, which initially were the most commonly used stents, only prevented long-term reclosure in 75% of cases. More importantly, the reason for reclosure was discovered not to be related to the original cause of coronary artery disease, but rather the result of neointimal (smooth muscle) growth in reaction to the foreign metal body, that is, the stent itself.

At that time, surface analysis techniques were used to determine if the outer-layer topography of bare metal stents affected the rate and prevalence of reclosure. Surfaces were frequently examined using scanning electron microscopy and three-dimensional noncontact profiling to assess whether or not microscopic level variations had any function affect on host material.

It remained clear, however, that an alternative solution was needed to address the problem of restinosis. The drug eluting stent was therefore conceptualised. It is in this area that surface analysis has continued to play a valuable role, particularly in assessing drug distribution.

Using surface analysis techniques, the composition, integrity and thickness of the coating can be analysed to see how these affect drug elution. This helps to develop and produce a stent with an optimal and consistent elution path.

Dynamic secondary ion mass spectrometry (DSIMS) is an important tool used in this area. It enables drug distribution with depth, whether immunosuppressive, antiproliferative or antimigratory, to be monitored. Assume, for example, the presence of nitrogen in the structure of a drug component. By using DSIMS to obtain simple elemental or molecular information from the sample, different areas of the stent surface (outer nanometres) and the depth of the coating can be monitored for specific nitrogen-containing ions (charged molecules) to show drug distribution, see Figure 1. Similarly, if the coating is layered in its structure to facilitate delayed drug release, compositional data obtained from DSIMS can be used to determine how the drug is distributed within the specific layers.

Next-generation devices

Research in the future is likely to focus heavily on producing stents that are completely biodegradable. This will provide initial restenotic prevention and then complete reabsorption of the stent to eliminate the thrombosis risk and allow complete healing. In this scenario, nondestructive surface analysis techniques such as X-ray photoelectron spectroscopy and secondary ion mass spectrometry (SIMS) could prove vital. The reason for this is that nondestructive techniques produce/cause no disruption to the surface to obtain data. Monitoring critical elemental data from the stent surface over a defined period can therefore determine the real-time rate of biodegradation.

Where degradation is found to be too fast or too slow, time of flight secondary ion mass spectrometry (ToFSIMS) imaging can be used. It will identify potential surface contaminants that could be causing the problem; it can also identify compositional variations that may be the cause.

Another area likely to benefit from surface analysis techniques is where metal stents are fabricated with more complex kinetic release profiles. These profiles can include multistep, pulsatile, extended release, multidrug and stacked layers of degradable polymer/drug mixes to produce more versatile and programmable drug-eluting stent systems.

In these complex systems, components need to be assessed for their affect on the host material and in relation to each other. For example, one particular coating/drug combination may result in optimum burst rates because of the porosity of the outermost layer and the specific drug used. Alter the drug used and the same porosity may generate quicker, undesirable burst rates.

This can be studied by using ToFSIMS imaging and DSIMS depth profiling. These techniques will monitor surface drug distribution pre- and post-elution testing. XPS surface analysis can be used to quantitatively examine the subsequent surface functionality. Thus, qualitative and quantitative results can be achieved. This is why surface analysis has proven to be an invaluable tool in the past ten years of stent development and why it is likely to continue to help develop this particular area of technology.

Other application areas

In fact, any drug treated medical device that is designed to elicit a certain response or avoid a certain reaction from a human host can benefit from surface analysis techniques. Orthopaedic implants, transdermal patches and even some contact lenses now on the market all fall into this category. In each instance, combining the techniques used, that is, measuring coating thickness for consistency with SIMS technology and measuring surface functionality with XPS/SIMS techniques, enables researchers to gain a clear picture of various factors affecting the interaction between host and device.

Improved devices

Returning to stent technology, however, it is clear the role that surface analysis techniques have played to date. This author has witnessed a growing requirement from the stent research and development sector. Interest in the benefits that surface analysis has to offer is increasing in reaction to a market demand to improve devices and the creation of a new generation of stent.

Shaun Bainbridge is Sales and Marketing Manager at CSMA Ltd, Queens Road, Penkhull, Stoke-on-Trent ST4 7LQ, UK, tel. +44 1782 764 269, e-mail: shaunbainbridge@csma.ltd.uk, www.csma.ltd.uk.