In this piece Lucideon’s polymer technology consultant, Richard Padbury, looks at some of the challenges in polymer analysis and how manufacturing changes the complexity for cardiovascular devices in the polymer market.
What is coronary artery disease (CAD)?
CAD is a significant contributor to cardiovascular disease (CVD), which resulted in an estimated 17.9 million deaths in 2016.1 CAD is caused by a build-up of fatty deposits on the artery walls, causing inadequate supply of oxygen rich blood to the heart which increases the risk of heart attack. The standard treatment for CAD is a non-surgical percutaneous coronary intervention (PCI) that uses a collapsed polymer balloon guided by a thin wire into the narrowed section of the artery. Subsequently, the balloon is inflated to force the artery open and restore blood flow to the heart. The artery may also be supported by a cardiovascular implant known as a stent.
Stent technology
The main generations of stent technology include bare metal stents (BMS) and drug-eluting stents (DES), which are primarily composed of metallic substrates, and bioabsorbable stents (BAS) synthesised from bioresorbable polymers. A significant drawback of BMS is that the materials are typically incompatible with the vascular environment, which leads to an increased risk of restenosis. These drawbacks are overcome by DES through the release of anti-proliferation drugs from absorbable or non-absorbable biopolymer coatings. As an alternative, BAS were designed to reduce the long-term complications associated with BMS, as their degradation byproducts are eliminated by the body during resorption, as the artery naturally heals.2 However, market adoption of BAS has been slower than anticipated due to concerns with lower radial strength, stent recoil, stent deployment and higher costs. From a materials perspective, a lot can be learned from these products and the inherent properties of different materials developed for medical devices.
Polymers
Polymers are characteristically different from metals because of their viscoelastic behaviour. This leads to distinct time dependencies, melting points and thermal transitions which determine whether the polymer acts like a flexible, rubbery material or a brittle glass. These characteristics can be subtly modified by changing a few molecules or blending and copolymerising with other polymers. However, it is important to note that when we improve one aspect of a polymer it can be at the cost of another, either in terms of mechanical performance, degradation time or biocompatibility.
Polymers also have vastly different microstructures compared to metals, and across different polymer chemistries, which range from purely amorphous to semi-crystalline. A team of researchers at Massachusetts Institute of Technology (MIT) used Raman spectroscopy to analyse the microstructures of BAS.3 Their study showed that discrete variations in polymer chain orientation and crystallinity can form from the stent surface to the stent core. They attributed these fluctuations to thermal and mechanical strains that occur at each manufacturing step and after deployment. Ultimately, this can lead to non-uniform degradation and a decrease in structural integrity which could promote larger deformations that block or disrupt blood flow. This work has important implications for strut thickness, a critical design feature of BAS. The thickness of the struts is directly tied to the mechanical properties of the polymer. If the mechanical properties of the polymer are insufficient then thicker struts are required, but this increases the risk of turbulent blood flow and thrombosis. With a greater understanding of microstructure, it may be possible to modify processes to enhance molecular orientation, eliminate microstructural irregularities and increase the material’s stiffness. Subsequently, this could promote the development of thinner BAS (<100µm), using the same materials, with performance characteristics comparable to BMS and DES.
Most medical devices, from guidewires and catheters to balloons and stents, go through numerous process steps during high-throughput manufacturing. Every manufacturing step has its own unique set of process conditions which increases the chance of picking up contamination, defects and changes in morphology and microstructure. When failures do occur, the root cause can be confounded by the multiple process steps, and corrective actions become more difficult to prescribe. Nevertheless, there are numerous thermal, mechanical and chemical methods validated for medical devices and, as demonstrated by the MIT study, it is important to acknowledge that material structures and failure modes vary across different material types and that the resolution of the analytical instrument is an important consideration when characterising device quality.
In short, stents are a good lesson in polymer process-structure-properties and design for medical devices. All factors must come together to deliver a break-through performance.
So, what does the future hold for the cardiovascular market?
BAS technology should not be discounted all together; there is still an emphasis on improving long-term patient outcomes, which can certainly be achieved if these products can be refined and made safer. However, the use of conventional DES will likely continue, and studies are now showing comparable performance between DES and drug coated balloons.4 Major innovations could come from coatings and the type of pharmaceutical actives used.2 Advancements in coatings, bulk additives or surface modifications with varied surface charge, topography, and antibacterial and anti-thrombogenic properties may become important advances for guidewires, catheters and a wide range of cardiovascular devices. A particular focus area at Lucideon is the development of drug free antibacterial materials, with the aim of overcoming challenges associated with antibiotic resistant infection.
Based on what we have observed at Lucideon, we anticipate that regulatory evaluations will become ever more stringent. Examples include demonstrating coating durability, thickness, uniformity and coverage to new levels - along with the safety, stability, dose and release rate of actives. Additional requirements include particulate evaluations during deployment and withdrawal simulations and following radial fatigue testing. Obtaining the data to support these requirements often needs new methods and techniques, and indeed this is something we are being increasingly tasked with by manufacturers. No matter which direction you turn, it is essential to understand the differences between materials and the various analytical capabilities available to characterise device structure, properties and design.
References
- https://www.who.int/en/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds)
- Frost & Sullivan. (2016, March 30). Next Generation Stent Technologies. Overtaking Traditionally Dominant Bare-Metal Stents (BMS), Drug-eluting (DES) and Bioabsorbable Stents Race Ahead.
- http://news.mit.edu/2018/study-reveals-why-polymer-stents-failed-0226
- https://doi.org/10.1016/S0140-6736(18)31719-7