Medical Device Daily Contributing Writer

SAN FRANCISCO — Julio Palmaz, MD, of Palmaz Scientific (Dallas), addressed current coronary stent design problems and discussed solutions for the future of these implantable devices during the "Coronary stent design and device development" portion of the Transcatheter Cardiovascular Therapeutics 2009 conference, pointing out that many in the industry have forgotten basic lessons about the bare metal balloon-expandable stent (BMS).

Palmaz was the first and last speaker in a series of presenters who discussed stent development.

"BMS is the gold standard in vascular stents," he said. "It is the only time-proven (more than five-year follow-up data) vascular stent. And it is the stent for which we have the largest amount of information. Metals offer a safe, long-term implant while polymer coatings of metal implants may cause non-specific chronic inflammatory changes."

Eugene Sprague, PhD, of the University of Texas Health Science Center at San Antonio presented "The role of the endothelial cell in determining device biocompatibility." He suggested that, "Most current strategies to reduce restenosis are directed at killing or at least inhibiting arterial wall smooth muscle cells. Yet extensive evidence indicates that an intact endothelium naturally limits smooth muscle migration and proliferation to control wall architecture."

Sprague concluded that "the different materials used in intravascular implantable devices such as stents exhibit a wide range of fibrinogen and cellular-binding levels across different materials, but a consistent predictable level for each individual material. A stent with cellularly defined grooves will enhance re-endothelialization rates and restoration of a functional endothelium."

Robert Schwartz, MD, of the Minneapolis Heart Institute, said "Pigs are telling us something," in a session called "Polymers as vascular implants. "There is a terrific amount of inflammation from synthetic polymers." He suggested that next-generation surface coatings might be polymers that are "non-biodegradable and non-bioactive; that they be based on a peptide-type backbone and non-degradable. Thus far, this approach shows resistance to cell adhesion for greater than 90 days."

Schwartz also said, "Configuration matters. Biocompatibility is more than materials." He noted that the industry has spent more than 50 years looking for a perfect passive coating material. "It's time to ask: Does such an implementation exist? Is it even possible? Do we want to inhibit reactive cells, or control them?' Biomimicry is a potent future."

Adnan Kastrati, MD, of Deutsches Herzzentrum, Technische Universität (Munich), noted that clinical evidence strongly suggests that a stent's design affects restenosis in a session called "The clinical relevance of stent design."

"Bad passive coatings may offset the advantage of thin struts," Kastrati said. "On the other hand, local delivery of good drugs may offset the disadvantage of thick struts. Several stent characteristics have a relevant impact on outcomes achieved with BMS. Although this impact is extremely reduced for DES, improvements in stent design will continue to enable more complex and successful interventions."

Renu Virmani, MD, of CVPath Institute (Gaithersburg, MD), focused on "Designing the bare-metal or polymer-coated stent of the future from the lessons of the past." In her presentation, she reviewed the parameters of stent design, pointing out that design considerations are critical because design is related to stress in the vessel wall. Virmani reviewed data that compared close-cell versus open-cell design. A published study showed that an open-cell design may offer inadequate scaffolding in a complex bend situation, while a closed-cell design may cause a concave surface of the stent resulting in scaling.

"Stent design determines neointimal formation," she said. "The number of struts against the arterial wall is a determinant of neointimal growth." Drug release kinetics are determined by the chosen polymer as well as stent strut surface geometry. She said there are several key considerations for designing the bare-metal or polymer-coated stents of the future: a closed- or open-cell, strut thickness and geometry, single versus overlapping for drug release and polymer choice and release rates, which determine the level of toxicity, especially with a cytotoxic drug.

Juan Granada, MD, of Columbia University Medical Center (New York), presented "Impact of stent delivery mechanisms on vascular injury and responses." He said that the self-expandable (SE) mechanism allows dynamic remodeling of the stented segment in complex anatomies. He offered several conclusions: The latest generation coronary self-expandable stents initially achieve less lumen gain compared to balloon-expandable (BE) stents. This initial difference in lumen size is compensated for over time, finally achieving lumen areas comparable to BE stents. Chronic stent expansion seems to be reduced by more than half in the latest generation of coronary devices. Adjunctive balloon dilatation induces a short-term increase in lumen, but with no clear effect on benefit in clinical outcomes. Finally, small clinical studies still underway show that the restenosis rates are comparable to the latest generation of BE stents.

Due to its intrinsic mechanical properties, Granada said, SE stents have the potential to improve the outcomes of PCI by inducing less injury at the time of implantation and better device apposition as the vessel remodels.

In a session on "Bioactive stent coatings: Surface modification technologies and beyond," Chaim Lotan, MD, of Hadassah-Hebrew University Medical Center (Jerusalem), emphasized that clinicians need three things from a stent: biocompatibility, low restenosis and low stent thrombosis. He defined biocompatibility as the ability of a material to perform with an appropriate host response in a specific application.

"Theoretical advantages of a bioactive stent may not always be translated into a clinical advantage," Lotan said. "A combination of a bioactive surface with drug-eluting and/or other modes of surface modification might help to improve stent performance."

Steven Bailey, MD, of the University of Texas Health Science Center at San Antonio spoke about "Physical vapor deposition of metals for the fabrication of implantable vascular devices" during which he said that current problems with bare-metal stents include, but are not limited to, macroscopic and sub-microscopic contamination and that current problems with polymer-based stents include non-uniform polymer coating, webbed polymer surfaces leading to stent expansion issues and polymer delamination. Bailey made the case that new stent hybrid materials will improve biologic outcomes by surface modifications that improve endothelialization, alter protein attachments and substitute alternative binding sites.