Biocompatibility Of Metallic Stents Research Articles

Prototyping sutureless shape-memory valve stent via integrated 3D printing

Abstract Transcatheter aortic valve replacement (TAVR) has increasingly emerged as a forefront option for treating aortic valve diseases. However, the currently prevalent valve prostheses used in TAVR typically involve stitching biologic leaflets onto metallic stents, which introduces challenges in the durability of leaflets and the biocompatibility of metallic stents. This work proposes an integrated additive manufacturing method for prototyping sutureless prosthetic aortic valves that combine shape memory polymer (SMP) stent and hydrogel valve leaflets. The SMP stent exhibits sufficient toughness to maintain structural integrity upon shape memory programming, while the Fe3+-treated hydrogel leaflets possess sufficient swelling resistance to ensure dimensional stability. Finally, the proof-of-concept valve stent is successfully fabricated by integrated 3D printing and validated via an in vitro hemodynamic experiment. Overall, our approach holds promise for prototyping sutureless polymeric valve stents for future generations.

Autologous cell therapy for enhanced endovascular repair after coronary stent implantation

A little history Michael Kutryk is the name of the interventional cardiologist and scientist who had this dream. As early as the late 90s, Michael had the vision that it could be most desirable to heal strut coverage specifically with functional endothelial cells in order to improve the biocompatibility of metallic stents. The concept of designing a “prohealing” device with accelerated restoration of endothelial continuity was born at least at first in the mind of its inventor, but was quickly supported by bench and preclinical experiments. By this time, Kutryk had left Canada to join the group at the Thoraxcenter in Rotterdam as a post-doctoral fellow (Figure 1). During this period, Patrick Serruys was experimenting with local drug delivery with sweating balloons and, needless to say, he was immediately taken with Kutryk’s idea. Perhaps somewhat naively, they hypothesised that endothelial progenitor cell capture could prevent at one and the same time both thrombosis and restenosis. It should be remembered that in those early days of stenting, the issues were immediate stent thrombosis and early restenosis, at rates of 20% each! Nobody at that time was anticipating that late thrombotic events would plague the future anti-restenosis solutions, initially vascular brachytherapy and now drug-elution. The Genous technology invented by Kutryk and embraced by Serruys was developed and supported by Orbus Medical Technologies, and later acquired by Neich, an Asian-based company to form Orbus-Neich. Major research and development efforts eventually led to the First-In-Man trial that was published in 2005. The illustration (Figure 2) depicting the principles of the therapy was indeed very convincing, to the point that it was eventually included in the patient informed consent document for further studies. It shows how the stent is covered with a biocompatible matrix to which murine, monoclonal, anti-human CD34+ antibodies are covalently attached. The antibody is specific to the surface antigens, present on circulating endothelial progenitor cells creating an immuno-affinity surface for preferentially capturing these circulating cells. CE mark approval was obtained on August 11, 2005. The HEALING clinical trial program was designed and indeed completed, and publications appeared at an increasing pace. The device also underwent a number of technical iterations including the use of a cobaltchromium stent platform, to replace the bio-engineered R-stent.

Localized arterial wall drug delivery from a polymer-coated removable metallic stent. Kinetics, distribution, and bioactivity of forskolin.

Coronary stenting is associated with two major complications: subacute thrombosis and neointimal proliferation resulting in restenosis. Our hypothesis is that the biocompatibility of metallic stents can be improved by coating with a polymer membrane that delivers agents that favorably modify the local arterial microenvironment. This study evaluates the kinetics, distribution, and bioactivity of the model drug forskolin delivered to the local arterial wall by a polyurethane-coated removable metallic stent. Stents were used in rabbit carotid arteries (n = 20) for as long as 24 hours. The quantity of forskolin bound to the stent decreased exponentially with a half-life of 5.8 hours. Blood concentrations peaked at 140 +/- 39 pg/microL at 4 hours. The adjacent arterial media contained 60 +/- 39 ng/mg, which was 380- and 460-fold greater than the contralateral carotid media and the systemic blood, respectively (P < .0001). Media forskolin concentrations declined exponentially over time with a tissue half-life of 5.0 hours. Drug distributed throughout the vessel wall with decreasing gradients in the radial and axial dimensions consistent with a diffusion process. Removal of the stent was associated with a 100-fold decline in media forskolin concentration within 2 hours. Forskolin release was associated with a sustained 92% increase in carotid blood flow and a 60% decrease in local arterial resistance compared with coated control stents (P < .005). In another set of rabbits (n = 14) using a carotid crush injury, flow-reduction model, forskolin prolonged the time to flow variation and occlusion by 12-fold compared with the use of bare metal stents and 5-fold compared with the use of polyurethane-coated stents (P < .0001). A polymer-coated metallic stent can deliver forskolin to the local arterial wall in high concentrations relative to the blood or other tissues. High local drug concentrations are dependent on maintaining stent-to-tissue gradients. The delivered drug is biologically active, demonstrating vasodilating and antiplatelet properties.