Simulating the Release Mechanism in Drug-Eluting Stents

Boston Scientific is a leading developer of medical devices and technologies aimed at diagnosing and treating a wide range of medical conditions. The company is known for its innovative solutions in the healthcare sector, particularly in the field of cardiovascular health. Boston Scientific's team of engineers, including Travis Schauer and Ismail Guler, are at the forefront of medical device design and development. They focus on creating advanced medical devices that improve patient outcomes and enhance the quality of healthcare. The company's recent work on drug-eluting stents is a testament to its commitment to innovation and excellence in medical technology. By leveraging computational models and simulations, Boston Scientific aims to better understand and optimize the mechanisms of drug release in stents, ultimately improving treatment for patients with cardiovascular disease.

Treating arteries in the heart that have been blocked by plaque is a common challenge for medical professionals. Known as stenosis, this condition restricts blood flow to the heart, resulting in symptoms such as shortness of breath and chest pain. It is sometimes resolved using stents, which are small, mesh-like tubular structures designed to treat blocked arteries. They are usually placed in the coronary artery and expanded with a balloon catheter to keep the artery open. While stents are successful at holding arteries open, an artery can re-narrow because of excessive tissue growth over the stent. This is called restenosis and is the body’s natural healing response, but it can actually impede recovery. Thus, drug-eluting stents were developed to deliver medicine — which acts to reduce cell proliferation and prevent the unwanted growth — into the artery tissue. These contain a coating composed of medicine and a polymer matrix designed to provide a controlled delivery; each strand of the stent mesh is surrounded by this coating. Stent designs have improved dramatically in recent years in an effort to reduce restenosis rates, but much remains unknown regarding the release process.

Travis Schauer, Ismail Guler, and a team of engineers at Boston Scientific used COMSOL Multiphysics® to model a stent coating and investigate the release profile of the medicine. They aimed to understand the rate at which the medicine diffuses out of the coating and into the vessel tissue, as well as the factors influencing this process. Using the Optimization Module in COMSOL, they fit their simulation as closely as possible to experimental data curves. The stent coating modeled by Schauer and Guler is a microstructure with two phases: a medicine-rich, surface-connected phase and a phase with drug molecules encapsulated by a polymer. The development of this microstructure is affected by the solubility of the drug, the drug-to-polymer ratio, and the processing conditions during manufacturing. When the stent is inserted into an artery, the medicine-rich phase quickly dissolves and diffuses into the tissue, leaving behind interconnected cavities (pores) in the polymer coating. Meanwhile, the molecules encapsulated by the polymer diffuse more slowly. Schauer and Guler idealized the complex geometry of the coating microstructure in their model, which consists of a pattern of cylindrical pores filled with solid medicine surrounded by a polymer shell containing both the dissolved drug and solid drug encapsulated by the polymer. The molecules diffuse radially and axially, and the microstructure geometry only changes radially at the boundary between shell and pore. Using COMSOL allowed them to easily customize their model and focus on understanding the transport phenomena at hand. They performed simulations for two release profiles, in vitro and in vivo cases, seeking a description of the cumulative release of the medicine. They compared experimental data to the release profiles generated in their simulations to confirm their findings.

• The use of COMSOL Multiphysics allowed the engineers to easily customize their model and focus on understanding the transport phenomena at hand, rather than spending time on cumbersome programming.
• The simulations provided valuable insights into the release mechanism of the drug-eluting stents, helping to tailor the release profile to achieve a desired outcome.
• The customizable boundary conditions available in COMSOL Multiphysics enabled the engineers to easily add the necessary terms and implement appropriate interface conditions.
• The model parameters, such as the polymer shell thickness and retardation coefficient, were refined using the Optimization Module to obtain the best fit between the model results and the experimental data.
• The results of the simulations showed good agreement with experimental data, lending confidence to the appropriateness of the idealized model and providing a better understanding of the release process.