Medical Device & Diagnostic Industry Magazine
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An MD&DI  March 1998 Column

R&D HORIZONS

Engineers teach versatile materials how to work in the body.

Imprinted in the crystal structure of shape-memory alloys is a metallurgical intelligence. These alloys remember and return to past shapes with nothing more than a simple reminder—an increase or decrease in temperature, a pull, or an electrical shock. This ability to memorize shapes allows the creation, for example, of a stent that can be cooled into a compact form and inserted through a catheter into the weakened part of a blood vessel, where body warmth returns it to its expanded shape. Plates made from such a shape-memory alloy (SMA) might be used to pull fractured bone together or to correct spinal scoliosis. Surgical instruments can be contorted to designated shapes, then made to return to their initial form. A small electrical current might be used to induce tiny pumps and syringes to contract in reversible cycles.

NICKEL-TITANIUM

Perhaps the greatest challenge facing developers of SMA applications is not the discovery of new alloys, but rather the realization of how to take full advantage of an alloy already at hand. Nickel-titanium (or nitinol, as it is commonly known) has been around for some time, but only recently have engineers come to appreciate its true potential. NiTi is the heavy hitter for medical applications, accounting for virtually all shape-memory products in the field.

Superelastic NiTi components resist kinking and crimping. Photo courtesy of Raychem/Memry Corp. (Brookfield, CT)

"In terms of having shape-memory properties and being biocompatible, nickel-titanium probably has the market tied up for quite a while," says Alan Pelton, PhD, a research fellow at Nitinol Devices and Components (Fremont, CA), a subsidiary of Johnson & Johnson. The increasing attention given to minimally invasive surgery and advanced techniques, including angioplasty and laparoscopic surgery, should open the door to expanded applications of this metal.

The shape-memory phenomenon, originally observed at the Naval Ordnance Laboratory nearly 40 years ago, allows devices made of NiTi to assume one shape when cold and another when heated. Alloys that have "double memory" exhibit a reversible effect, with heat causing a reaction that is reversed by cooling. The phase that is stable at low temperature is called martensite, and the one stable at high temperature is called austenite. The advantage of shape memory is demonstrated in the Simon nitinol filter, a vena cava filter used to trap blood clots. The device is cooled until it collapses and is then inserted into the vena cava, where body heat causes it to deploy into an umbrella-shaped filter. Developed in the 1970s, the filter has been implanted successfully in hundreds of patients.

The first step in manufacturing an SMA device is to fashion the material into a specific shape. Next, it is heated to about 500°C. The elevated temperature forces the atoms into a very compact and regular pattern; when cooled, the crystalline structure reverts to its former shape. The memory of these different shapes is created by heating and cooling the alloy until the crystallographic relationship between the two phases is set. Nitinol transformation temperatures range from about —50° to 166°C.

In final form, the device achieves a preset shape when heated beyond its transformation temperature and then assumes the alternate shape when cooled below that temperature—in essence remembering different shapes associated with high and low temperatures. A side benefit is that these implants are extremely resistant to damage because their shapes are atomically programmed. "Bump a nitinol stent and it springs right back," says Darel Hodgson, PhD, president of Shape Memory Applications (Santa Clara, CA). "Bump a stent made of stainless steel, and it becomes a plug."

Although two-way memory offers advantages, it is not without its drawbacks. For instance, the alloy must be "taught" the two shapes, which requires any of several different methods. One is shape-memory cycling, whereby the alloy is cooled, deformed, and then heated repeatedly until the shapes are drummed into memory. Overheating can result in a loss of memory. Also, long-term fatigue and stability characteristics are not well understood. As a result, device manufacturers may prefer one-way memory using a biasing force acting against the "remembered" shape to produce an alternate form upon cooling. These devices have demonstrated excellent response and long-term stability up to millions of cycles.

SUPERELASTICITY

Changing shapes may be the most striking characteristic of NiTi, but this alloy also exhibits superelastic properties, making it exceptionally flexible. NiTi is capable of absorbing huge amounts of strain energy and releasing it as the applied strain is removed. "This is the same transformation as shape memory," says Hodgson. "The difference is that instead of changing shape in response to temperature, you put enough force on the material so that it deforms to a different shape and then, when you reduce that stress, it goes back to the previous shape. So you get this shape-memory effect without changing temperature."

Guidewires made of NiTi are ideally suited to an environment increasingly concerned with reducing trauma to the patient. "Shoving a catheter into a vein is like pushing wet spaghetti into a hole," says Mac Schetky, PhD, chief scientist at Memry Corp. (Brookfield, CT), which supplies SMAs and fabricates medical devices from nickel-titanium. "A guidewire is needed—and the best ones are resistant to kinking and permanent bending due to superelasticity."

NiTi guidewires can be drawn down to a couple thousandths of an inch in diameter and still resist kinks, bouncing back from snags that might permanently deform a wire made of stainless steel. The alloy can also be made into tubes, which could be used to infuse fluids. Alternatively, the tubes can be cut into pieces and precisely sliced using a laser to create devices such as intravascular, tracheobronchial, biliary, and urethral stents. Indeed, stents constitute the single biggest area of development for nickel-titanium, says Schetky.

CURRENT AND FUTURE APPLICATIONS

Since the first medical application of nitinol some 20 years ago, developers have created a variety of different devices. One of the best known is the Mitek suture anchor used in orthopedic surgery to attach tendons, ligaments, and other soft tissues to bones. Through a small incision, surgeons hook the suture to the soft tissue, drill a hole in the bone, and insert the anchor, which expands with body heat to form a tight bond with the bone. Since 1989, when the device was introduced, more than 25 orthopedic and urological applications have been developed.

Other designers are working on a type of plate that can be screwed into two bones like a brace. "When the plate reaches body temperature, it shrinks and pulls the bones into tight alignment," says Schetky. Similarly, nitinol rods might be applied to the spine to correct scoliosis. "The surgeon would open the spine, bend the cooled nickel-titanium rods to the shape of the spine, then tie them with wire or suture to the individual vertebrae," says Schetky. "The rods try to recover their straight shape, exerting pressure in a straight direction along the spine."

Within five years, stents made from NiTi could reach 25% of the market (Nitinol Devices and Components, Fremont, CA).

Flexible and complex instruments, some of which are designed to go around corners, are now being used in laparoscopic surgeries. St. Jude Medical (St. Paul, MN) has developed tools that assume a shape at room temperature suited specifically for open-heart surgery. They revert to their original shape when heated during sterilization.

At present, NiTi is the only shape-memory alloy available to the medical device industry. Others made of copper, aluminum, and nickel; copper-zinc and aluminum; and iron, manganese, and silicon do exist, but these alloys exhibit unacceptable levels of toxicity. NiTi, on the other hand, appears exceptionally well tolerated by the body. Despite a high content of nickel, which is toxic, the strong intermetallic bond between this metal and titanium all but eliminates the risk of reaction, even in patients with nickel sensitivity. For those who remain concerned about nickel, Memry Corp., in collaboration with the National Institutes of Health, is working on a new shape-memory alloy—a titanium-based metal that does not contain nickel. "The alloy has been developed," Schetky says. "We're now working on the metal processing, developing procedures for melting, rolling, and drawing."

MANUFACTURING CHALLENGES

Biocompatibility aside, NiTi still presents some serious drawbacks. Foremost, the alloy is a manufacturing nightmare. NiTi is very sensitive to changes in composition. Ideally it is composed of half nickel and half titanium, on the basis of atomic number. Changing this balance markedly affects the material properties, with excess nickel strongly affecting the transformation temperature. "A change of one tenth of one percent in the nickel composition will move you about ten degrees centigrade from the transformation temperature," Hodgson says. "So you have to control the composition of these ingots to a couple hundredths of a percent to get the transformation temperature you want."

Moreover, common contaminants such as oxygen, carbon, and nitrogen can cause a shift in transformation temperature while degrading the mechanical properties of the alloy. As a result, a major challenge in dealing with NiTi is controlling its manufacture so as to produce the desired properties. Because of the hyperreactivity of the titanium in the alloy, all melting must be done in either a vacuum or an inert atmosphere to eliminate or at least markedly reduce the risk of contamination by oxygen or nitrogen. Manufacturers get around this problem through a variety of methods, including plasma-arm melting, electron-beam melting, and vacuum induction melting. Because contamination is less of a problem after ingots of the alloy have been made, forging, bar rolling, and extrusion can be done successfully in air. The ingots can be worked cold, but the alloy tends to harden quickly, which means annealing must be done frequently. Special tools are required to turn and mill the material, and welding, brazing, and soldering are also difficult.

Component design poses additional challenges. Because the mechanical and physical properties of SMAs change, no single set of property values can be used in a design. And even these properties, which depend on the temperature of the material either above or below the transformation point, are affected by composition. Contaminants and differences in the ratio of nickel and titanium can also vastly change the behavior of the alloy.

Companies venturing into this area of development—either alloy production or device design and manufacture—must have a thorough knowledge of shape- memory behavior and might be advised to bolster that knowledge with specialized computer programs. Nitinol Devices and Components has a group dedicated to providing finite element analysis in the design process. With computerized assistance, knowledgeable engineers, and a little common sense, the design of nitinol devices is manageable. "You don't need a super expert," Pelton says. "The main jump is you don't treat it like stainless steel, and you don't treat it like a rubber band. It's somewhere in between."

Cost presents a further barrier to development. Nitinol is one of the most expensive materials used in medical devices. Suppliers may charge about $20 per foot for tubing, which might be cut into 1-in. pieces. These pieces are then laser sliced, for example, into stents and sold for $100. The price jumps to several hundred dollars when the stent is combined with a catheter-delivery system, which then may be sold to the hospital for $1000 or more. Cost per unit may go down, however, as use of the material rises. Today, only about 5% of stents are made from NiTi. "There is a tremendous opportunity in stents and other vessel strengtheners," says Hodgson, who predicts that within five years the percentage of stents based on NiTi could jump to 25% of the market.

MICROACTUATORS

NiTi is also being used in combination with other materials. One recent application is its deposition onto thin-film silicon. The materials are being fashioned into the tiniest medical devices known—microelectromechanical systems (MEMS). Applying heat by means of a low electrical current coaxes the alloy into a preset shape, which can be used to drive a miniature pump, for example, or to compress a syringe. Cutting off the electrical current causes cooling and transformation to the alternate shape.

"Per unit volume, nitinol is the most powerful actuator available today," says Jacques Matteau, CEO of TiNi Alloy Co. (San Leandro, CA). Actuators made from such thin films and NiTi might be used to infuse drugs, or they might be placed in strategic locations in the body to assist circulation. Such actuators might also be machined into a gripper that samples tissue for biopsy or grabs an implant, such as a coil, for retrieval. Long-range research by engineers at NiTi Alloy Co. is focused on developing a microstent, a stent that could be used in extremely small blood vessels. It, like MEMS, would be fabricated with both nitinol and thin-film silicon wafers. "This is very much a cutting-edge research effort," notes Matteau.

The key to making such miniature devices successfully, Matteau adds, is finding ways to manufacture them economically in large quantities. The same is true of all nitinol-based products. Rather than developing new shape-memory alloys for medical applications, the challenge is to come up with ways to use more effectively the one that has been at hand for the better part of 40 years.

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