Ortho Device Surface Treatments Seek Infection Avoidance

With orthopedic devices and instruments in high demand, and new design technologies and manufacturing methods coming to the forefront, the need for advanced surface modifications and coatings for components and implants has never been higher. R&D investment is also on the rise, especially for learning more about implant-immune system interactions at the cellular level. For example, over the last 10 years there has been tremendous growth in knowledge of how the immune system attacks every implant material. In turn, medical device manufacturers (MDMs) are starting to show serious interest regarding the immune system’s decisive role in implant fixation and performance. There is a keen focus within the orthopedic field to make better implants with properties that enhance bone integration with the surrounding tissue and reduce infection. To meet these growing needs, orthopedic manufacturers and their partners have developed state-of-the-art nanotechnologies that mimic immune function, making it possible to create bioactive surfaces for implants and other devices.

For example, Promimic—a Swedish firm with a U.S. division in Austin, Texas, that provides innovative surface solutions for medical devices, implants, and other components—has developed HAnano Surface, a 20-nanometer-thin implant surface treatment composed of crystalline hydroxyapatite (HA) particles. “These crystals have the same shape, composition, and structure as HA found in human bone,” said Ulf Brogren, CCO for Promimic.

HAnano Surface is 1,000 times thinner than traditional HA coatings and “can be applied to nearly all implantable materials from machined titanium, additive titanium, cobalt chrome, stainless steel, polyetheretherketone [PEEK], and also additive PEEK, creating a super hydrophilic surface that improves osseointegration of the implant,” said Kathy Siri, sales manager for Danco Medical, a Warsaw, Ind.-based provider of surface preparation and finishing technologies, including anodizing, electropolishing, and passivation for medical devices and components. To date, more than 1.4 million implants with the surface are in clinical use.

There is also a steady release of new implant devices that stay in contact with the blood and, therefore, must be hemocompatible; examples are total artificial hearts, ventricular assist devices, vascular grafts, and prosthetic mechanical heart valves.

“When blood interacts with foreign surfaces, it triggers a complex series of events,” said Arjun Luthra, commercial director for BioInteractions, a Reading, U.K.-based R&D company that develops advanced and specialized coatings for medical devices and instruments. “These events include protein adsorption, platelet adhesion and activation, coagulation, and thrombosis.”

Replacing devices compromised by clots or inflammation of the body’s tissues is a highly risky and expensive procedure. This has led to the search for high-performance materials that are hemocompatible, improve device performance, and reduce risks to patients. “These include bioactive coatings, which have the ability to enhance the body’s acceptance of implanted devices and improve the device’s ability to function properly for longer within the body,” added Luthra.

Spinal implants is one of the fastest-growing orthopedic fields. The use of new biomaterials, advanced production processes, and new surface treatments has made this market one of the most innovative in recent years. This is in part due to the 3D printing of cages made from titanium and PEEK to improve fusion treatments. Additive manufacturing and 3D printing (AM/3DP) can now make implants with complex geometries that have micro-porous in-growth structures and textures to facilitate osseointegration. Proactive MDMs and their contract manufacturers (CMs) and finishers work closely together to deepen their understanding of the impact of surface technologies on 3D-printed substrates, as well as the potential for breakthrough discoveries.

For AM/3DP, “material homogeneity and exterior surface uniformity are crucial for successful application of surface technologies, specifically when the surface treatments can penetrate the top few microns of the substrate,” said Michael Gianfrancesco, vice president of engineering and technology for Precision Coating, a Hudson, Mass.-based provider of surface modification solutions for medical wire, devices, and instruments. “We have already been providing ion implantation and lasers nano-texturing services on 3D-printed substrates.”

What OEMs Want

For most MDMs, high quality, low costs, and fast speed to market are at the top of their lists. Other product priorities vary depending on their markets. Some companies want solutions for fixation failure; MDMs that focus on trauma seek easier removal of temporary devices. Additional common requests are for assistance with improving osseointegration and resistance to wear, corrosion, and infection.

One way to speed up time to market is to streamline the regulatory submittal process by eliminating setbacks or resubmittals. The FDA is becoming more vigilant, which means MDMs want their quality and attention to detail to stand out. Therefore, the more the manufacturing process is supported and validated with data, the faster the approval will be. Increasingly, MDMs and their CMs are asking for that back-up data, including proof of tolerances and the amount of material removed.

“We pay strict attention to customer specifications and can hold tolerances to 0.0002 inches,” said Luke Almeida, COO for New England Electropolishing, a Fall River, Mass.-based provider of high-precision electropolishing and finishing for medical devices, surgical implants, and assemblies. “We verify incoming tolerances on parts using digital micrometers and customer-supplied gauges and verify removal during a formal first-article sampling and throughout our process.”

To ensure top quality, New England Electropolishing utilizes advanced pre-cleaning technologies to clean medical components that are laser-cut and have a layer of slag or dross from the laser-cut features. “Pre-cleaning and descaling are as important as electropolishing to ensure parts are contaminate-free and can be electropolished effectively,” said Almeida. “We use pickling and ultrasonic cleaning to clean contaminates and heat-affected zones to ensure parts are properly prepared for electropolishing.”

Along the same cleanliness theme, New England Electropolishing utilizes an electropolishing procedure on parts that have heat scale resulting from heat treatment in non-atmospheric conditions. This process removes heat scale and prepares parts for a secondary electropolishing step to ensure a high level surface finish that is both cosmetically appealing but also free of contaminants on a micro-compatibility level.

Other unwanted materials in medical devices include contaminants called “forever chemicals,” which include per-and polyfluoroalkyl substances (PFAS) because they break down very slowly. Their persistence in the environment and prevalence across the country make them a serious concern for human health and the environment.

“Polytetrafluoroethylene [PTFE] is one of the most common PFAS materials,” said Matthew E. Thompson, business development manager for precision components, medical, for Oerlikon Balzers Coating USA, a Schaumburg, Ill.-based provider of coatings and other solutions for medical device manufacturers. “For this reason, we have customers that are exploring options to replace PTFE coatings in devices. Typically, these coatings are used for lubricity and friction reduction. As possible alternatives to PTFE, we are looking at existing carbon-based coatings, such as diamond-like carbon [DLC] coatings.”

Ultimately, MDMs are highly motivated to find easily available, high-performance, multifunctional, and extremely stable coatings technologies. The use of catheters, heart valves, vascular grafts and stents, as well as many other essential support systems for the body, continues to grow. MDMs seek coatings that can mitigate potential health risks, protect the body, and improve the performance of the device, all while ensuring the body’s acceptance of a foreign object. “The use of coating materials is as important as the design of the device itself,” said Luthra. “As we enter the age of coatings, advancements in multi-functioning and non-leaching coatings will be crucial features of enabling medical device manufacturers to design new innovative solutions into their therapies with enhanced performance and implantation time.”

Processes and Procedures

To drive innovation and broaden the scope of potential applications, surface-preparation companies are pushing the boundaries of complexity for coating structures, the range of substrates on which coatings can be deposited, and the functional chemistry of coatings. Typically, physical vapor deposition (PVD) and plasma-assisted chemical vapor deposition (PaCVD) coatings require metallic substrates that are conductive, temperature compliant (suitable for 400°F to 900°F processing temperatures), and can withstand vacuum (have a high vapor pressure). The first two requirements (conductivity and temperature) are typically the biggest restraints.

Now, however, Oerlikon Balzers Coating USA has developed new PVD coating machines that utilize a proprietary filtered plasma accelerator technology. “This allows us to deposit ta-C-style DLC films at temperatures below 212°F, with no requirement for a conductive substrate,” said Thompson. “This means, for example, that we could coat a very temperature-sensitive substrate like nickel-titanium without adversely affecting its memory characteristics. DLC films could also be deposited directly onto a wide range of polymers, elastomers, and ceramics—substrates that are simply not possible to coat with other PVD or PaCVD equipment.”

Anodization is a standard treatment for coloring titanium parts. The process removes the naturally occurring and invisible surface oxide layer to produce good colors for visual identification of titanium implant components in the operating room, where surgeons can quickly gather the color-coded parts for a given size of implant. “The anodizing process does not use any dyes or pigments; instead it creates a new oxide layer on the surface of titanium that refracts light, which in turn, creates different colors based on the thickness of the oxide layer,” stated Chris Boothe, founder of Multi-Etch, a Saratoga Springs, N.Y.-based provider of a popular technology used for color anodization.

The Multi-Etch process is widely used by MDMs to prepare medical and dental implants for color anodization and etching shape memory alloys. Multi-Etch is also effective at removing unfused particles from titanium parts produced with additive manufacturing, without affecting critical tolerances. “In the shape memory alloy field, Multi-Etch has been proven to be highly effective for cleaning the interior chambers in 3D-printed nitinol actuators, which cannot be accessed through conventional methods,” Boothe added.

Electropolishing is another critical finishing process for the orthopedic industry that improves surface finish and overall product performance. Electropolishing boosts manufacturing efficiency, enhances product durability, makes parts easier to clean and sterilize, and increases corrosion resistance. Tiny (±0.0002 inches) surface defects and contaminants left behind by the machining process can be easily eliminated with microscopic precision, leaving critical metal parts free of microburrs, microcracks, and other defects, while enhancing durability and corrosion-resistance.

“MDMs are often not aware that electropolishing does more than improve the surface finish of stainless-steel medical devices—it also achieves passivation, eliminating the need for additional steps in the production process,” said Almeida.

Surgeons (and therefore, orthopedic device companies) are often concerned about reflectivity in the operating room. Because many implant parts and components are made from stainless steel, which can create glare, “more device manufacturers are asking for matte, non-reflective finishes,” said Almeida. To meet this need, New England Electropolishing developed its proprietary ElectroMatte process, which delivers all the benefits of electropolishing, as well as a non-reflective matte finish. This finishing process meets all ASTM Standards for electropolishing and passivation. An alternative to tumbling, ElectroMatte finishing also deburrs and passivates parts while maintaining precise rates of removal. The process is ideal for metal or stainless steel medical device assembly components and arthroscopic, endoscopic, and laparoscopic surgical components.

Surface treatment using ion implantation is gaining attention because it can be applied to virtually all types of metal implants to enhance wear and fretting resistance, as well as reduce surface friction. Precision Coating’s proprietary IonGuard ion implantation technology creates a hard, low-friction titanium surface with a wear performance comparable to cobalt-chrome devices. “The process utilizes direct ion beam bombardment to increase durability and hardness, reduce the coefficient of friction, and create a hydrophilic surface,” said Gianfrancesco. “This modification technique is not a coating, so there is zero risk of delamination and the surface morphology of the device is maintained.”

Laser nano-texturing is a permanent way of improving the osseointegration of implants. Two main factors that lead to implant failure are insufficient osseointegration and bacterial infections. Current surface coatings and surface modification techniques are incapable of providing long-term stability because they break down over time, making it harder for cells to adhere and survive. “Laser surface texturing is recognized as the most promising method for the production of biocompatible, antibacterial, and suitable surfaces for advanced bone mending due to offering accurate and permanent control over surface topography, morphology, wettability, and chemistry,” said Maziar Khatami, a former professor in the Department of Periodontics at the Mazandaran University of Medical Sciences in Iran. “This approach can provide micro- and nano-texture patterns for a broad variety of biomaterials, creating a surface roughness ranging from macro-roughness [Ra scale around 10µm] to nano-roughness [Ra scale <200 nm].”¹

Along the same research lines, Purdue University engineers have developed a laser nanotexturing process that enhances the antimicrobial and bone integration capabilities of titanium orthopedic implants. The first step creates a nanotextured surface on implants that improves their ability to integrate with bone cells, resulting in a 2.5-fold increase in bone formation compared to surfaces of untreated titanium implants. “The technology allows us to not only immobilize antibacterial silver compounds onto the surface of the titanium implants but also provide a unique surface nanotexturing that allows better settle attachment mineralization,” said Rahim Rahimi, lead researcher and assistant professor in Purdue’s School of Materials Engineering.²

Material Successes

The potential for groundbreaking innovation in surface treatments lies in understanding how the immune system interacts with implant devices at the cellular level. This knowledge leads to the development of immuno-compatible surface coatings such as Implant Surfaces’ IntimateBond Osteoblast titanium coating. The material is nanoengineered to maximize direct osteoblast on-growth to the entire surface of the implant, including graft channels. “IntimateBond is an immuno-compatible surface, proven in-vitro and in vivo and in well over 50,000 implantations,” stated David Hughes, CEO for the Longmont, Colo.-based provider of specialty surfaces for medical implants and devices. “It has the specific nano and sub-nano construction to control the attachment of the right proteins to prevent fibroblast formation and trigger the cascade to form osteoblasts and have them attach to and grow from the implant surface.” These surface coatings can be applied to a variety of spinal and orthopedic implants, including machined and 3D-printed PEEK and titanium-based devices with a wide range of geometric configuration, texture, and porosity.

MICRALOX is an anodic coating surface modification that was developed by Precision Coating. It improves the longevity of reusable aluminum surgical instruments and can withstand high temperature/high pH sterilization and auto wash cycles. “Over the past 10 years, we have seen MICRALOX grow to a substantial portion of our anodic coating business, with accelerated adoption for hand-held surgical instruments, cases, and trays,” said Gianfrancesco. In some situations, MICRALOX has extended the usable life of products by up to 25x—for example, conventional test methods for anodizing, such as salt spray, did not cause any MICRALOX failure after 18 months of 24/7 testing.

Antibiotics, vaccines, and other drugs help treat infections, but they are becoming limited in their overall impact due to drug resistance. BioInteractions’ TridAnt Enhanced Antimicrobial Coating is an antimicrobial solution that works alongside other measures to prevent a wide range of infections and protect patients over the long term. This surface kills a broad spectrum of pathogens (including drug-resistant bacteria, MRSA, and SARS-Cov-2) “by targeting microbes [prokaryotic cells],” said Luthra. “It is the first known medical device technology to kill a wide range of pathogens in under 15 seconds and prevent the formation of biofilms for up to 365 days with a non-leaching process that provides a constant level of protection over long periods of time.”

Other surface-treatment successes include:

• Researchers at the Institut National de la Recherche Scientifique in Quebec, Canada, have developed an implant coating made from shrimp shells, collagen, and glass that promotes healing and lowers the risk of rejection. A key coating component is copper-doped phosphate glass, which stimulates blood vessel formation and bone reconstruction.^3,4
• A coating material consisting of hydroxyapatite (HA) and graphene oxide (GO) was developed using electrophoretic technology and tested on titanium surfaces. The results showed the HA-GO-surface induced osteogenesis as indicated by improved cell adhesion, proliferation, osteogenic differentiation, and osteogenesis-related gene expression.⁵
• Leaching of cobalt ions into the human body is a serious health risk with medical implants made of cobalt-chrome-molybdenum (CoCrMo). To reduce this risk, Ionbond has developed its PVD-deposited Medthin coating, which fully encapsulates the CoCrMo substrate material and reduces cobalt release by more than 98%.⁶

Moving Forward

The big challenge in orthopedic implants is not just whether a device made with certain materials and textures will be accepted by the human body, but can surgeons, orthopedic device manufacturers, and their partners find ways to eliminate infection in the surrounding tissues that often leads to implant failure?

“Long-term antibacterial protection is not possible with these traditional drug coatings because a large portion of the loaded drug is released in a short time,” Rahimi said. “There also is often a mixture of microbes that are found in implant-associated infection; it is essential to choose a bactericidal agent that covers a broad spectrum.”²

Researchers must find ways to prevent implant-associated infections, especially as biofilms become more resistant to the powerful antibiotics used to treat them. “New intervention strategies to prevent and treat orthopedic implant-related infections are the future,” said Luthra. “Various technologies to prevent implant infection are still evolving. New ways to develop the best bioengineering method to bond antimicrobial coatings securely to medical device surfaces over their lifecycles are coming to light in the medical device industry.”

“The biggest misconception is that biocompatibility as defined by ISO 10993-5 is enough to ensure good implant fixation and performance,” concluded Hughes. “The reality is that the immune system attacks every biocompatible material and the results of that attack can compromise the implant’s fixation and performance. The solution is interacting directly with the immune system.” 

References

1. tinyurl.com/m4aauh3s
2. tinyurl.com/5yzupk3p
3. tinyurl.com/3wyze22e
4. tinyurl.com/2e5vpn78
5. tinyurl.com/2jwbej62
6. tinyurl.com/odt231106

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Mark Crawford is a full-time freelance business and marketing/communications writer based in Corrales, N.M. His clients range from startups to global manufacturing leaders. He has written for MPO and ODT magazines for more than 15 years and is the author of five books.