Medical science has come a long way from the days when coronary artery bypass graft surgery was the sole method for treating blocked coronary arteries. While the emergence of balloon angioplasty in 1977 offered patients an alternative to heart bypass surgery, a new strategy for performing percutaneous coronary procedures made its debut in 1986 with the first implant of a coronary stent. Since then, stents have been used to perform the vast majority of percutaneous coronary interventions, with more than 900,000 coronary stents implanted annually in patients to treat heart disease. Several hundred thousand peripheral stents are also implanted
Advanced Machining Processes Are Key to Manufacturing Tomorrow's Stents
While early stents were made from stainless steel, the implantation of stents in smaller or more-complex vessels and the heightened demand for increasingly intricate design features have changed the stent design and development landscape. Today, designers and manufacturers of stents are relying on such shape-memory materials as nitinol because of its superelastic ability and superalloys such as cobalt-chromium because they offer higher strength than stainless steel, enabling the fabrication of smaller structures with smaller features. As a result, doctors can now perform percutaneous procedures in previously inaccessible vessels. This development, in turn, is keeping design engineers, materials suppliers, and manufacturers alike on their toes as they continue to develop shrinking profiles, complex features, and a range of novel materials for both coronary and peripheral stents.
One Stent Does Not Fit All
Stent design and material selection are so intertwined that determining which one is primary is a little like deciding which comes first--the chicken or the egg. Ultimately, both the design of the stent and the type of material used to realize it depend on the clinical application, according to both Steve Burpee, COO of Burpee Materials Technology (BMT; Eatontown, NJ), and Brad Beach, vice president of research and development at Burpee Materials Technology and Flexible Stenting Solutions (Eatontown, NJ). "A lot of what we focus on is properly designed stents for a particular indication," Beach explains. "Thus, coronary stents are very different from peripheral stents, which may be very different from certain types of stent grafts. It really comes down to understanding this and properly designing components and devices to meet whatever the needs of the application are."
|Nitinol stents and delivery systems from Burpee Materials Technology are used in vascular therapy applications.|
A designer and manufacturer of both balloon-expandable and self-expanding nitinol stents, BMT fabricates components and devices for treating aortic aneurysms, conducting early-stage neurovascular therapy trials, treating peripheral artery disease (PAD), and performing other applications. However, while many traditional first- and second-generation stents have achieved some procedural and longer-term success when used in the coronary arteries, they have not been as successful in lower-body arteries such as the superficial femoral artery (SFA) and the tibial arteries. Because these leg arteries are often tortuous and subject to complex motion in most PAD patients, plaque is present over much longer lengths than in the coronary arteries.
To design stents for SFA applications, BMT and other companies turned to the development of nitinol-based shape-memory alloys. More effective than balloon-expandable stent technologies, nitinol stents can be implanted in longer, more-intricate stretches of artery than can traditional coronary or balloon-expandable stents. "That's an example in which the anatomy and the medical need really dictate the best approach as far as design and materials are concerned," Burpee remarks.
However, the first generation of nitinol stents used in SFA applications has generally been inadequate because of design issues, according to Burpee. "Because of the way they're constructed or the way they exit a delivery catheter, they are likely to fracture in vivo or be deployed nonuniformly by physicians." In response, BMT developed a nitinol stent designed specifically for long, tortuous anatomies. That design, dubbed the Flexstent, led to the formation of Flexible Stenting Solutions.
One of the Flexstent's design features is its reconstrainability, which enables the stent to be recaptured back into its delivery catheter. "Given a properly designed delivery system, you have the potential to recapture and redeploy this stent, especially when treating peripheral diseases," Beach says. "The SFA can be long and diffuse, and there's the potential that the stent will not be deployed in the correct position or that it will be too long or too short." Reconstrainability allows clinicians to retract and relocate the stent midway through the procedure, avoiding these pitfalls.
Unlike stent designs with freestanding struts, the Flexstent features struts and strut apexes that are all connected to other struts, enabling the physician to pull the stent back into its delivery catheter and reposition it if it's not located or seated properly. This feature also prevents unconnected strut apexes from poking outward from the stent body, a deficiency of other designs that can injure vessel walls. Designed to be conformal and flexible at the same time, this stent is suitable for negotiating small, moveable, and tortuous arteries, Beach states. "If you picture a popularization of a DNA helix, this stent basically has a helical path of struts along its entire length, and all those strut ends are connected to downstream or upstream struts by helical coils," Burpee adds. "That's unique. That's something that other stent designs do not have."
The Thinner the Stent, the Better
For many years, stainless steel was the material of choice for designers, developers, and manufacturers of balloon-expandable stents. However, in the last five to 10 years, a new population of alloys has emerged that feature improved radiopacity while offering mechanical properties similar to those of stainless steel as well as corrosion resistance equivalent to or better than that of stainless steel. Above all, superalloys such as cobalt-chromium have taken off in balloon-expandable stents because of their ability to form miniaturized features.
|Optimal performance of nitinol peripheral stents depends on careful material selection and expert architectural design.|
"Typically, the motivation in balloon-expandable stents for going with superalloys has been the ability to reduce the cross-sectional strut dimensions--the width and, particularly, the thickness of the struts," remarks Todd Dickson, president of Lumenous Device Technologies (Sunnyvale, CA). "According to some data, it seems that there's a relationship between clinical outcomes and the amount of metal or how the metal is deployed within the artery," he adds. "Stent makers have adopted the use of less metal or have spread it out better throughout the lumen. This has prompted a proliferation of activity in the field of superalloys."
Providing stent design and manufacturing services to medical device OEMs, Lumenous is active in the fields of vascular and nonvascular stents, including balloon-expandable and self-expanding, or nitinol, stents. From the 1990s to 2003, the company designed approximately 75 different stent products for a range of applications. In numerous cases, it adapted a particular architecture to a variety of clinical indications.
The company is on the cusp of designing stents with thinner features. "The trend toward thinner structures--trying to do more with less metal--has driven the move toward high-modulus materials such as superalloys," Dickson explains. "This trend enables designers to get away with less cross-section to improve stent deliverability and hemodynamics, reduce the introduction of foreign material, and also hopefully improve the endothelialization of the stent." The purpose of this shift is twofold: to enable physicians to enter smaller body structures and to improve outcomes in what Dickson describes as bread-and-butter stent applications--well-established applications involving 2.5- to 4.0-mm-diam coronary arteries with discrete lesions.
The fortunes of thinner stent designs could soon be boosted by the likelihood that coronary stenting via the wrist, a technique that involves introducing a stent through a very narrow artery, will become increasingly accepted. Also known as the radial approach, this method was validated in April 2011 with the publication of the radial vs. femoral access for coronary intervention study (RIVAL), which demonstrated that the radial and the traditional femoral approaches are similarly effective for treating coronary disease. The growing recognition of radial stenting, Dickson notes, will favor lower-profile designs that offer better trackability and flexibility.
Stent design requires a clever combination of finite element analysis, a variety of bench tests, intuition, and design-build-test iteration capability, Dickson says. "The key to efficiently steering a design safe to port lies in knowing which questions need to be asked--and answered--at each point along the way and which evaluation method is most suited for the question of the moment."
In self-expanding stent applications, nitinol is increasingly being called upon to perform extraordinary tasks, Dickson notes. It must stand up to very complicated stress states and cyclic loads that threaten to fatigue and fracture implanted devices. But to achieve grades of nitinol that can stand up to such stresses, special materials processing expertise is usually required. Providing that expertise to the medical device industry is what Memry Corp. (Bethel, CT) is all about.
|The average inclusion size for stents made using Memry's microclean nitinol is roughly 2 µm, with 99% of all inclusions falling below 9 µm.|
Producing various types of nitinol alloys, Memry distinguishes itself by the quality of its nitinol, remarks Matt Rowe, the company's vice president of sales and marketing. "The microcleanliness of our nitinol is of significant value to the marketplace, especially when it's used to design implantables."
Nitinol microcleanliness is rated according to the presence of nonmetallic inclusions in the material and its porosity, Rowe explains. The ASTM F 2063-05 standard sets the maximum allowable dimension of inclusions, which typically include nonmetallic carbides and intermetallic oxides, at 39 µm and the maximum area fraction at 2.8%. But based on multiyear production data statistics, Memry's nitinol has a maximum inclusion size below 26 µm and a typical area fraction of inclusions below 2.0%. Moreover, the average inclusion size of Memry's material is approximately 2 µm, while 99% of its inclusions are less than 9 µm, according to the firm.
The size and distribution of the inclusions play a critical role in nitinol quality, Rowe says. The company's experience in melting and processing nitinol and in minimizing the inclusions that form when the nitinol is melted is critical to dictating how robust the end product will be from a fatigue standpoint.
Memry's customers seek to ensure that their devices are deliverable using ever-smaller delivery systems, Rowe states. And to decrease the size of these delivery systems, designers must ensure that the implant can be crimped down sufficiently to maintain a small cross-section, or 'crossing profile.' "Device designers develop certain implants with very thin struts or other fine design features that often include very small cross-sections," Rowe adds. "Thus, it's not hard to appreciate that these very small structures are highly sensitive to the presence of inclusions, which represent areas of potential fracture. To avoid such fractures, device designers are keen to find the cleanest material possible."
Reducing a stent's profile is also a function of the type of material used to manufacture it. While Memry offers a regular binary grade of nitinol, it also produces a ternary nitinol alloy consisting of nickel, titanium, and cobalt that provides greater stiffness and enables design engineers to achieve greater miniaturization. "If you want to make a product with a certain radial force--a force that is exerted outward on the inside of a vessel wall--and you want to reduce its profile so that you can load it into a smaller delivery system, you can reduce the wall thickness of the implant or reduce other dimensions," Rowe notes. "But in doing that, you're trading off radial force for size." However, by adding cobalt to the nitinol alloy, engineers can create a thinner component or strut while maintaining the desired amount of radial force. "This is useful for applications designed for implantation in very small vessels, such as neurovascular, cardiovascular, or peripheral endovascular applications," Rowe says. "It's useful anywhere in which the goal is to reduce the profile and the overall size of the device."
Miniaturization is crucial for the future of stent design, placing special demands on materials development and manufacturing techniques. For example, while abdominal aortic aneurysm stent grafts are now delivered through 14-, 16-, 18-, 20-, or even 22-French systems that require a small surgical incision, the next goal is to develop a truly percutaneous system. "That's something in the range of 12 French--where you will not have to perform a cut-down on the patient's vessel but actually approach it from a true percutaneous standpoint, as you would any other interventional procedure," Rowe says.
Future Stents: Going, Going, Gone
Besides designing stents with smaller features and profiles, the medical device industry is atwitter about the emergence of bioresorbable stents--especially following last year's announcement that Abbott's Absorb bioresorbable vascular stent implanted in a New Zealand man dissolved as intended, leaving behind a healthy vessel. Since then, the stent has gained CE Mark approval in the European Union and is headed for additional trials in Japan, Latin America, Asia Pacific, and Europe, where a 500-patient trial has been scheduled.
"We've been involved in the design and fabrication of polymer-based bioresorbable structures," remarks Dickson from Lumenous. "The potential of bioresorbable technology is very compelling because it represents the potential of being able to deliver a therapy and then get out of the way. Regardless of how the next dataset looks, we're going to be seeing more of this technology in the future." Nevertheless, despite the technology's promise, many device companies have adopted a wait-and-see attitude toward it, Dickson adds, and they are exercising more caution than with other technology bandwagons in the past.
Rowe concurs that bioresorbable stent technologies are critical. A stent's objective, he says, is to hold an artery open and allow continued coronary blood circulation. Ultimately, it helps improve the overall outcome of the angioplasty procedure. "But stents are permanent implants and their presence in the vasculature can cause a host of issues such as unwanted vessel geometry or obstructed--jailed--side branches," Rowe adds. "Using a resorbable stent, you gain the benefit of maintaining vessel patency, but the product will eventually disappear. Thus, if you can open a vessel, deliver a drug, and then have the stent go away, that's really nirvana."