Dr Richard Padbury, senior technology consultant, Lucideon discusses important considerations and challenges for manufacturers developing BioAbsorbable Stents (BAS).
BAS – going nowhere?
BAS hold a lot of promise as an alternative to Bare Metal Stents (BMS) and Drug Eluting Stents (DES), however, structural and mechanical concerns have meant that adoption of BAS has been slower than anticipated. Nevertheless, recent studies from patient trials, using Abbott’s Absorb BAS, have shown promising results in peripheral vascular applications, giving BAS technology a fresh perspective.
Why bioabsorbable?
In the coronary market, BAS were initially designed to reduce the long-term complications associated with BMS such as late-stage thrombosis. A further drawback of BMS is that the materials are typically incompatible with the vascular environment, which leads to an increased risk of inflammation and restenosis. This is overcome via the application of BAS because the degradation by-products are eliminated by the body during resorption, as the artery wall naturally heals. Although these drawbacks can be overcome by DES (which release anti-proliferation drugs from biopolymer coatings), the stent still remains.
There is a continuous need to improve long-term patient outcomes, which can be achieved with bioabsorbable materials due to their inherent capability to safely support tissues as they heal and repair, before leaving the body over a controlled length of time. Because of these properties, bioabsorbable materials have also been developed for applications beyond the cardiovascular world, including orthopedic devices such as pins and screws, ligament and tendon repair, surgical applications ranging from tissue reconstruction and augmentation patches to sutures and wound closure devices and emerging applications such as scaffolds for tissue engineering.
Despite these exciting advances, bioabsorbable devices provide a platform to highlight the general challenges of optimizing polymer process-structure-properties and medical device design. All factors must come together to deliver a break-through performance.
What’s the challenge?
Polymers are characteristically different from their metallic or ceramic counterparts because of their unique viscoelastic behavior. This leads to distinct mechanical properties that depend on time, temperature and thermal transitions which determine whether the polymer acts like a flexible, rubbery material or a brittle glass. PolyLactic Acid (PLA), a common bioabsorbable polymer used in many of the applications mentioned, has a glass transition temperature (Tg) of 60-65°C. This leads to brittle behavior at physiological temperature (37°C) which means PLA devices can easily be damaged during processing, handling or during surgical deployment.
Polymers also have vastly different microstructures across different polymer chemistries, which range from purely amorphous to semi-crystalline. Discrete variations in polymer chain orientation and crystallinity can form from the surface of the device to its core. These fluctuations can be attributed to thermal and mechanical strains that occur during processing and even after surgical deployment. For bioabsorbable materials, this can lead to non-uniform degradation and a decrease in structural integrity which could promote larger deformations and medical device failure.
What can be done to overcome these challenges?
Despite their viscoelastic behavior and complex microstructures, polymers are attractive materials because of their tunability. They can be subtly modified by changing a few molecules or blending and copolymerizing with other monomers. For example, the same PLA can be copolymerized with PolyCaproLactone (PCL) to form a block copolymer with a much lower Tg compared to PLA alone. With a greater understanding of microstructure, it is also possible to modify processes to enhance molecular orientation, eliminate microstructural irregularities and enhance the overall properties of the polymer. Additives can also be blended into the polymer in different forms, e.g. fibers and particles, which can serve a range of multifunctional attributes, from providing additional mechanical strength, to radiopacity so that devices can be visualized during surgery. 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.
I am having difficulties during manufacturing, what should I do?
Here at Lucideon, we are frequently asked this question and, as materials science experts, we understand the complex processes researchers and engineers will need to go through to understand their challenges and overcome them. Lucideon works closely with partners to test and characterize a wide range of medical devices and materials and have seen first-hand the complexities of bioabsorbable technologies.
Most medical devices 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. But it is important to acknowledge that material structures and failure modes vary across different applications and that the resolution of the analytical instrument is an important consideration when characterizing failed devices.
What are some of the most important considerations?
In general, when a medical device fails during or sometime after manufacturing, the goal is to compare the failed material to a previously known ‘good’ state or a highly controlled standard with no thermal or mechanical history. In order to extract the most reliable information it is important to consider sample size, sample preparation and handling, and choice of analytical method. With sample size, assessing whether you have sufficient availability of samples for analysis ensures the question posed stands the best chance of being answered. This includes appropriate sample sizes from various stages of manufacture, as well as failed components, as this is often crucial towards systematically ruling out various factors and failure modes. With sample preparation and handling, one of the most important risks is unintentionally contaminating the failed material, which can unwittingly impact its characteristics and risk an erroneous diagnosis. Finally, with choice of analytical method, the suitability of different characterization methods, whether they are chemical, mechanical, thermal or image based techniques, depends on the type and number of analytes being investigated and if they can measure at the appropriate length scales or concentration ranges.
So bioabsorbable medical devices might not be ready to take the market by storm yet, but the hurdles to overcome are nothing new to polymer scientists. With successful trials from Absorb, a bioresorbable vascular scaffold and the numerous benefits to be gained from bioabsorbable medical devices, we are sure the discussion around them isn’t going away anytime soon.