From titanium and stainless steel to cobalt-chromium, tungsten, and tantalum, a host of metals is used in cardiovascular, orthopedic, and many other medical device fields. However, because metals and metal alloys are called upon to perform a variety of exacting functions in the body, they often require special processing to render them suitable for use in medical devices--especially if they are destined for implantable applications.

In stent applications, for example, metals must exhibit flexibility and strength, while in some orthopedic applications they must be capable of bearing loads. And because surgeons lack x-ray vision, they must be able to visualize the metal implants they place inside the human body using a variety of imaging techniques, necessitating the use of radiopaque materials. But above all, implant materials must be biocompatible, a natural property of such metals as titanium and stainless steel. Thus, advancing the design and development of implantable medical devices both presupposes and conditions the development of metals that resist fatigue, exhibit radiopacity, and demonstrate biocompatibility.

Resisting Metal Fatigue

"An implant's ability to function properly and provide therapeutic benefit usually depends on its structural integrity," explains Jeremy Schaffer, senior R&D engineer at Fort Wayne Metals Research Products Corp. (Fort Wayne, IN). For example, in a pacemaker lead, thin and conductive wires transmit signals to the implant, which sends an electric signal back to the heart through separate conductive wires contained within the same lead system. If the motion of the beating heart bends these wires mechanically, Schaffer adds, wire breakage can eventually occur, disabling the patient with potentially fatal consequences.

Specializing in materials and alloys for permanent implant applications, Fort Wayne Metals offers materials that must be able to withstand the forces exerted by the body. "Such implants must be able to remain in the body for years in the case of pacemaker leads, or even decades in the case of vascular stents," Schaffer says. "Resistance to these forces without failure is referred to as fatigue resistance."

To enable metal components to resist fatigue, Fort Wayne Metals employs what it calls the nanograin damage-resistant (NDR) process, a microstructural refinement technique that decreases the grain size of a metal, thus increasing the amount of stress or force required to permanently damage it. By decreasing a metal's grain size, the NDR process increases the metal's fatigue strength, or the load level at or below which it withstands a given number of loading cycles.

In order to achieve NDR-level refinement, metals are first deformed using cold-working processes, according to Schaffer. Cold-working produces significant stress in the material, which remains even after the process has ceased. It also produces millions of potential sites for grain nucleation, the process by which new crystals or regions of distinct atomic repetition form in very small volumes of metal. After the metal is cold-worked, it is heated to promote atomic diffusion of the constituent metal atoms. Performed at different temperatures based on the specific alloy and the cold-work levels, grain nucleation causes grain growth, whereby individual crystals or grains of metal consume and overtake other grains.

Known as recrystallization, this series of events leads to internal microlevel changes that impact a metal's external macrolevel properties, Schaffer notes. "When a metal is cold-worked and then heated, the recrystallization process does not happen instantaneously, but rather depends on the fourth dimension of time. NDR processing requires careful control of this fourth dimension to limit the process to mostly grain nucleation and little grain growth."

Most implantable alloys start as piles of scrap and virgin metal, which are heated and melted under controlled conditions into very large cylinders, or ingots, according to Schaffer. The grains in an ingot are often several inches in size. As the ingot is worked down into a 1-in.-diam rod, the grains are thermally and mechanically refined and reduced to the size of BB pellets. "By the time conventional wire is reduced and stretched into guitar-string-size wire, the grains are 10 times thinner than human hair, but they are still two orders of magnitude more coarse than NDR-refined grains," Schaffer adds. "NDR processing results in grains that are 1000 times thinner than human hair, or about 100 to 200 nm." This process produces implantable-grade metals that can resist the stresses exerted by bodily processes.

Touting Tantalum
While fatigue strength is a crucial characteristic of implantable-grade metals, other characteristics are also required. For example, implants must be constructed from radiopaque materials so that surgeons can see them under x-ray or other imaging techniques. One such material is tantalum, a metal that necessitates special processing methods to render it usable in medical device applications. Providing that kind of processing expertise is Tantaline Inc. (Waltham, MA).

"Tantalum has extraordinary properties," remarks Dean Gambale, president of Tantaline. "First of all, it's inert. That is, it does not react with the body, rendering it very biocompatible." In addition, tantalum is also a very dense metal, Gambale adds. "Weighing 50% more than lead, it's radiopaque--an important property for medical devices because it allows doctors to see it easily in x-rays. In fact, tantalum can block radiation even better than lead."

Tantaline processes tantalum for use in such implantable medical devices as cardiovascular stents and bone implants. However, by itself, the metal is difficult to machine or weld, and its mechanical properties make it difficult to form into the kinds of complex parts used in implantable medical devices. The company overcomes these limitations by depositing tantalum on intricately machined base metals, including titanium alloys, cobalt-chromium alloys, and stainless steel. "We can deposit tantalum on very complex parts--parts that otherwise would be impossible to fabricate using tantalum alone," Gambale says.

To exploit tantalum's radiopaque and biocompatible properties, the company vaporizes and grows it into the base metal, creating a tantalum surface alloy. "We create a gaseous atmosphere out of the tantalum metal and grow it into and on top of a complex machined component," Gambale comments. "Because our process is performed in the gas phase, the geometry of the base metal is irrelevant." Relying on the mass transfer of gases at high temperatures enables the process to metallurgically diffuse tantalum into the surface of the substrate metal and continue to grow the surface into a pure tantalum layer. Once this surface alloy is grown to a specified thickness, the component is inert to the body, radioopaque, extremely rugged, and durable, Gambale adds.

Tantaline's base metals exhibit a variety of different biocompatibility and toxicity levels, according to Gambale. However, the growth of the tantalum surface on the base-metal component ensures that only the tantalum comes into contact with the body. "Thus, from a contamination standpoint, the base metal is irrelevant because it's 100% encapsulated in the highly biocompatible tantalum surface," Gambale says.

Staying Wired with Tungsten
Tantalum is far from the only biocompatible and radiopaque metal. While a tantalum coating offers radiopaque benefits and excellent biocompatibility in long-term implantable applications, tungsten is suited for applications in which precise implant placement is critical, according to Josh Jablons, president of Metal Cutting Corp. (Cedar Grove, NJ). "With a density 70% greater than that of lead and nearly 20% greater than that of tantalum, tungsten is as radiopaque as gold,"
he explains.

Specializing in the manufacture of gold-plated tungsten wire, Metal Cutting offers wire grades with plating thicknesses ranging from 0.3 to 1.5 µm. "Previously, precious metals were commonly used in applications in which biocompatibility and radiopacity are crucial," Jablons remarks. "But with a density of 19.3 g/cm3--which is equivalent to that of gold, only slightly less than that of platinum, and significantly higher than that of palladium--tungsten has become an attractive alternative at a fraction of the cost of the precious metals."

An inert, largely corrosion-resistant metal, tungsten exhibits significantly higher tensile strength than other radiopaque metals, maintaining strengths ranging from 2400 to 3600 N/mm2 at more than 1000°C and with diameters as low as 0.0004 in., according to Jablons. And while platinum has a hardness of 549 MPa and gold a hardness of 216 MPa, tungsten has a hardness of 3430 MPa. Tungsten also has the highest melting point of any metal and the lowest vapor pressure and coefficient of thermal expansion of any pure-form metal.

Because of its radiopacity and resistance to heat and corrosion, tungsten is suitable for fluoroscopy, cauterization, endovascular interventions, electrodes used to perform deep-brain studies, and carotid procedures, Jablons says. "Its combination of hardness and tensile strength results in stiffer coils and more-steerable braids, making it suitable for coil tips, guidewires, electrodes, and probes."