Harder, Better, Faster, Stronger

Scientists at Peking University in China are printing three-dimensional (3-D) titanium bone implants designed to fit within individual patients’ bone structures. Researchers at the Missouri University of Science and Technology in the United States have created a glass material that can scaffold real, living, human bone tissue once implanted, and eventually degrades and converts completely into bone. And it now is possible to print—actually print, with a LaserJet printer—living cartilage tissue by laying down thin layers of cells on top of each other. Advances in science and technology not only are astounding in their own right, they also are coming increasingly rapidly. As biotechnology advances, all the processes that surround the development and application of the technology advance as well.

And although advancements in medical science certainly is positive, it can have unforeseen consequences on the industries responsible for bringing these applications to their intended purpose—the patient. The more advanced a material, and certainly the smaller the device it makes, the more difficult it becomes to test.

Polyetheretherketone (PEEK), a common polymer used in orthopedic implants, was first produced in 1978 in the United Kingdom laboratories of Imperial Chemical Industries. The polymer initially was conceived as a high-temperature-resistant, tough cable-insulation material. However, since commercialization of the polymer in 1981, the combination of ease of processing and excellent thermal stability and mechanical properties at high temperatures established PEEK as a general-purpose molding and extrusion material in both natural and reinforced forms for high-performance applications. As explained by S.M. Kurtz and J.N. Devine in their 2007 article “PEEK Biomaterials in Trauma, Orthopedic, and Spinal Implants,” due to its relative inertness, PEEK biomaterials are an attractive platform upon which to develop novel bioactive materials. Within the last decade, PEEK became broadly accepted as a radiolucent alternative to metallic biomaterials in the spine community. Sounds wonderful—and it is. But the reality is that in today’s age of incredibly wear-resistant plastics, for instance, it takes far longer to test for wear than it used to, causing some device testers to wring their hands.

Additionally, as Sherry Parker, director of technical services for medical devices at WuXi AppTec, a life-sciences outsourcing company based in China (U.S. headquarters are in St. Paul, Minn.), told Orthopedic Device & Technology, “Wear debris is now an added concern, since metallic particles could be nano-sized.”

“Nanoparticles-based bone substitutes require special imaging techniques to monitor the accumulation of particles in target organs like the liver or the kidneys,” said Jean Pierre Boutrand, general manager, scientific director, and director of international sales at NAMSA, a Northwood, Ohio-based medical research organization that provides laboratory services. “Tissue-engineered products require special cell marking techniques for further analysis of performance and distribution; drug device combinations require special pharmaco-kinetic models; and besides those technical adjustments, safety and performance testing for such innovative products require new thinking. We expect testing programs to evolve considerably in the future and fit better with these new types of orthopedic devices.”

Of course, Parker is alluding to the concern over all-metal hip implants that has emerged in recent years around products such as Johnson & Johnson’s DePuy Orthopaedic ASR metal-on-metal hip. Implants such as these have been alleged to deposit microscopic metal wear particles into the patient’s bloodstream and tissue surrounding the implant site, causing the need for revision surgeries, and at worst, severe illness and sometimes death.

These are the types of concerns that occupy the minds of orthopedic device testing professionals. Most orthopedic devices are designed to be implanted long-term into patient’s bodies, and therefore carry significantly more risk.

“The most challenging products are biological products,” explained Boutrand. “Not only because we expect these to become a big segment in the future, but because the safety hazards associated with such products are different from more traditional implants (for example, the risk for microorganism contamination) and the performance aspect might be more complex to address. Most test methods that have been developed for inert materials and require adjustments with biological materials are tested.”

Jim Rancourt, Ph.D., founder and CEO of Polymer Solutions Inc. (PSI), a polymer testing, materials analysis, and metals testing company based in Blacksburg, Va., said that original equipment manufacturer (OEM) client testing audits have become more in-depth. Though they were always thorough, he said, now they assess the analytical and testing facilities with greater scrutiny than ever.

“In earlier days, the way that I would see audits is that they focused a lot on the data and on the test that was done on their product,” said Rancourt. “That’s where the main focus was. Now the analytical lab is viewed as almost a production facility. They want to see, from beginning to end, from the time the sample comes in the front door, where it goes, who handled it, how you know who handled it, where it was stored, how it was stored, what the temperature was, training records of the employees, the analytical equipment, when was the equipment was calibrated. If a ruler is used somehow to generate a data point, they want to know how the ruler was calibrated and stored. And for professionals who do important, high-consequence measurements, none of that is unexpected. We always did or strived to do all of those correct things, but auditors weren’t looking quite that deeply years ago.”

Advancement Getting You Down?
Scientists at the Nano Surfaces division of Bruker Corporation, a Germany-based research and development company with U.S. offices in Billerica, Mass., specialize in white light interferometry testing methods. In fact, as Deepak Sharma, Ph.D., senior product marketing manager explained, this surgically precise process is really the only testing method Bruker needs to test orthopedic devices. The method tells them all they need to know about surface texture and other characteristics, which is what Bruker is concerned with. And in order not to scare off customers, Sharma said good humoredly, they refer to the method simply as 3-D microscopy or profilometry.

With this non-contact method of testing, where scientists are really just observing surface roughness, texture and wear, materials don’t matter.

“We use an optical technique, so we don’t even make contact with the part,” Sharma said. “We shine light on it and observe how the light scatters back and causes fringes when compared to an extremely smooth surface. We compare it to the surface we’re examining, and what we’ll get is interference fringes, which look like a badly tuned TV with contours moving through it. From that we can deduce the structure on the surface and the only thing that really matters to us is the reflectivity of the part to some
extent. There is nothing we have received in the orthopedic industry so far that we haven’t been able to get very good data on from 3-D microscopy. So whether it be plastics or metals, it doesn’t really matter to us. We use the same technique and we get the same level of accuracy in our testing.”

The contours formed by white light interferometry allow Bruker testers to determine whether surface damage consists of pits, scratches, spirals, etc. The testing instruments take detailed images of all the different regions of the device, and stitch them together at the nanometer scale.

Most often, Bruker will receive orthopedic devices to test for wear after tribology testing. This testing method, not performed by Bruker, simply performs numerous cycles of motion or exerts numerous cycles of friction on an implant simulating years’ worth of use. And here is where, as materials become more advanced, contract testing providers run into a problem.

“A massively recurring theme, not just in this market but in any market, is that clients want to be able to see nanometer level detail on large materials,” explained Sharma. “The reason is they want to measure wear and tear, and this is on everything from train wheels to camshafts in automobiles to hip joints. Ten years ago you could do perhaps a couple of weeks of repetitive action and measure how much the part has worn down. There may have been 10 to 20 microns worth of wear there. Materials and lubrication science has advanced so much and become so resistant to wear that wear and tear is becoming almost non existent. Say an instrument can only measure 10 microns of wear, and you get used to getting 10 microns of wear in two weeks—now it’s taking four months to get the same level of wear and tear. All of a sudden, the length and amount of times you have to keep those machines running goes way up, and therefore cost goes way up on doing that research.”

Bruker’s 30-year history in microelectronics expertise is of great benefit to the company when it faces clients who demand seemingly impossible levels of micro-level testing, said Sharma. Examining devices by the nanometer, which is one-billionth of a meter, is one thing, but scientists at Bruker can drill down to the angstrom level—one ten-billionth of a meter—with white light interferometry. Thus, Bruker is able to avoid getting slowed down by the slicker polymers and more resistant materials taking longer to show wear.

Besides being slowed down, inherently, by increased wear times of advanced materials, testing companies also face clients who simply demand a faster turnaround on an array of testing requests. 3-D microscopy can measure surface texture, but sometimes clients also want to evaluate the shape and form of an implant as well. In terms of testing, shape is the geometric structure of a device, while formation is the amount of contours and waviness exhibited in the device.

“One of the challenges we faced a couple years ago is a request to very rapidly measure multiple parts on a hip ball,” Sharma recalled. “It was on a production line and we had to measure five locations—north, south, east and west—and the top of the ball. We wanted to look at the nanometer levels surface texture and roughness at those five locations quickly. So we worked with [the client] a little bit and came up with an idea we liked. We brought in a robot arm and put our measurement head on in, which could be programmed arbitrarily to articulate around a table full of hip balls and basically measure all of them in five locations pretty rapidly.”

Other techniques that are used to measure surface textures, such as coordinate measurement machines or stylus measurement—a tactile method of measuring surface texture by running a needle along a surface and measuring vibrations—are not capable of measuring to the type of resolution white light interferometry can reach, Sharma said.

Adapting to Change
Advancements in device materials technology can mean much more expensive devices as well as skyrocketing costs for contract testing providers.

The first issue, more costly devices, can pose a particular challenge for device testing. How can a device be thoroughly measured, tested for biocompatibility, safety and wear and tear, and yet be kept intact for the OEM because it costs thousands of dollars per unit? Well, testers have to get smart.

“A lot of new medical devices are very expensive and so our clients prefer that we be able to handle and get reliable data on very tiny samples,” said PSI’s Rancourt. “If a particular product is small and worth $10,000 per unit, the client doesn’t want us to say that every time we do a test we need five of them. They want us to be able to do more with less.”

More with less, indeed. Rancourt explained that another one of the device testing industry’s biggest challenges in the past few years is that the devices are miniaturizing, creating challenges for running tests on small surface areas and with such little material to work with.

“What is really making things more difficult is that a lot of medical devices are becoming very tiny and multi-component,” Rancourt continued. “Catheters are a good example of multi-layer device. Each layer is a specific chemical structure with particular physical properties and our clients want us to take these things apart and figure them out. Drug-eluting stents are another example—a combination of metals, plastics, drugs, and not just one layer of polymer material or plastic, but many layers. Testing complicated structures, being asked to figure out chemical and physical properties of each component, and verifying the overall structures are as it should be—pretty challenging.”

But PSI is up to the challenge. One way of meeting new problems that need solving is collaboration, and Rancourt built that spirit into his company once he realized the need for change. The CEO’s Ph.D. is in chemistry with a focus on polymer analysis. However, as he rubbed elbows with colleagues at orthopedic device conferences and industry events, he realized that 80 percent of what he saw was metals-based, and only 20 percent was plastics based. He often was asked, “Do you do metals?”
which, as an analytical chemist, he understood to mean, “Do you do analysis and characterization of metallic based materials?” Realizing he was turning away business by answering “No,” he invested in making his originally polymer-focused company into a more sophisticated, all-encompassing materials analysis firm. Plastics and metals testing requires two very different sets of expertise, so Rancourt made the decision to invest in metals experts and metals testing capabilities.

“We’re seeing increasingly complicated devices,” Rancourt said. “A lot of devices are made of a combination of a material and a drug, or a combination of materials such as metal components and plastic components. If they don’t interact successfully, then the whole system is not successful. For us to be analyzing materials for medical device companies, it’s best if we’re comprehensive in our abilities to evaluate all of the components. It’s good for us from a business perspective, but from a quality perspective as well, these OEMs have to audit their suppliers and the more that we can do for a client to cover the range of needs they have, they can send one auditor here and capture the chemical and physical testing that we do on plastic, rubber, ceramics and metal materials.”

Bioabsorbable screws in a custom compression fixture. Image courtesy of Polymer Solutions Inc.

“The requirements [plastics and metals] are quite different, so the skill set is also different,” Rancourt continued. “One of the most basic differences is the strength and load-bearing capabilities of metals compared to plastic materials. The strongest plastic materials are never as strong as a metal in the same sample size would be. Second, very good plastic materials begin to degrade in the range of 300 degrees Centigrade, and for metals that’s not an issue at all. Of course for medical applications in the body, people aren’t exposed to temperatures as high as that, but those temperatures also set process limitations. Metals are processed typically at much higher temps than any polymer materials would be.
Plastics are very time and frequency sensitive—which is not to say metals are not—but at reasonable frequencies, a plastic can be very ductile or flexible, and at higher frequencies that same plastic could behave in a brittle manner. And at a low temperature, a plastic can be brittle and at a high temperature, flexible. Plastics are highly sensitive to changes in frequency and temperature compared to metals.”

PSI Metallurgist Alex Wensley explained PSI’s metals testing capabilities:

“We have two devices that we commonly use to measure the chemical characteristics of metals. This testing procedure is very important because very tiny elemental changes in metals can drastically change their properties. The XRF (X-ray fluorescence, both a technique and an instrument) is non-destructive. It shoots X-rays at the sample and then measures the X-rays coming back. The elements give off characteristic X-rays, so you can take a sample as small as 3 millimeters and shoot it with an XRF and within two minutes it will give you a very accurate composition of your metal alloy. There are a few limitations, though, since 3 millimeters is the smallest feature that it can look at. That’s when we can use the SEM (scanning electron microscope) and EDS (energy dispersive spectroscopy). From a physics standpoint, EDS is the same technique as XRF, where you shoot your sample with electrons and measure the X-rays it gives back, but it happens inside an SEM. The SEM has a small chamber and really can only really look at very small samples. The biggest thing we can put in there is about 1 centimeter tall. If it’s a bigger sample, very often we’ll have to do destructive testing to get it down to a small piece and put it in the SEM. The SEM and EDS combined have a very broad range of elements that they can look at. It can tell you if it’s a polymer, albeit not what kind of polymer. It will tell you if it’s a metal and what metals are in an alloy. Its limitation is that your sample has to be in a vacuum, conductive and small, but it can see a very broad range of elements, give you a very good idea of what elements are there, and why they’re there.”

The importance of interdisciplinary expertise at testing facilities also was pointed out by WuXi’s Parker: “While heavy metals analysis makes sense for metal materials and ceramics, metals can also be present in polymers and plastics as colorants and residual catalysts.”

Device complexity doesn’t end with metals and plastics. Drugs are incorporated, as well as bioabsorbable materials, which require further consideration when it comes to testing methods. For instance, PSI was approached by a company recently that wanted to test its bioabsorbable screws under physiological conditions. The screws had to be tested under specific temperatures, specific pH levels, with salt content, and under the stress of cyclic loading.

“We had to build and verify the performance of a custom test fixture to address that specific need,” said Rancourt.