Ranica Arrowsmith, Associate Editor03.23.16
A great source of angst within the orthopedic device space in recent years has been the effect of metal implants. Metal-on-metal hips have been found to deposit tiny metal fragments in surrounding tissue, causing infection and sometimes even death. Metal implants, such as fracture fixation pins, that have to be inserted and then removed later create the need for revision surgeries; and some metal implants prevent patients from undergoing certain medical imaging tests such as magnetic resonance imaging (MRI). These realities have fueled the market for bioabsorbable materials such as polylactic acid (PLA) and polyglycolic acid (PGA), both of which are polymer materials.
These materials do not offer the same strength capabilities titanium implants might, for instance, but their purpose is not to remain in permanent implantation. While in place, however, resorbable implants should be able to provide the required level of strength, rigidity, and/or flexibility, depending on the application.
“There is a definite shift towards the use of resorbable implants, wherever possible, and sophisticated processing methods are achieving more with existing materials,” Stephen Duffy, business development manager for Proxy Biomedical Ltd., told Orthopedic Design & Technology. “Proxy Biomedical has developed Bio-XT processing technology to reinforce resorbable implants, including composite materials that are loaded with ceramics. This technology is presenting opportunities in next-generation implant design, from lower profile implants to more porous designs and stronger implants with the potential to address load bearing indications. By using existing materials with an established clinical history, the regulatory burden is reduced and speed to market improved. I expect that we will see the proliferation of absorbable implants, with the benefit of technologies such as this, as well as greater use of bioactive materials.”
In 2014, researchers at the University of Florida developed magnesium as a possible alternative for metal implants that could be resorbable as well as strong enough to provide adequate support while in use. The pin developed by Michele Manuel, associate professor of materials science and engineering at the university, not only breaks down but also aids healing.
“We don’t always want to put in a metal implant and leave it there forever,” Manuel said. “The idea with this pin is that it would dissolve over time, and after it’s finished, your body is basically in the same state it was before you had an injury. Everybody knows someone who has an implant in their body that they wish wasn’t there,” Manuel said. “Surgical pins don’t have to become permanent fixtures in the body. Magnesium builds bone, so it can function both as a pin and as a nutrient. You have to have magnesium to live, and many people take magnesium supplements, so this is a good orthopedic application. It’s not only an implant that serves a medical need in terms of fixing bones, it’s also serving a nutritional need as well, so that’s why you see a lot of activity in the surrounding tissue.”
The use of magnesium isn’t new, Manuel said. In the early 1800s, physicians experimented with magnesium implants but ran into problems because magnesium produces hydrogen as it breaks down, which creates hydrogen gas bubbles under the skin that are clearly visible. Physicians of the era tried to remove the hydrogen gas with syringes but eventually gave up until new, improved metals were developed.
The trick to using magnesium, Manuel said, is controlling the rate at which it breaks down to give the body time to absorb the hydrogen.
“Your body can handle the hydrogen, just not in large doses, so pockets form,” Manuel said. “So if we can slow down how fast the magnesium degrades so it releases hydrogen more slowly, the body would take up the hydrogen the way it would take up any other gas and release it.”
In lab tests, Manuel has compared the magnesium pin with clinical implant materials. Surgical pins are shaped like screws, so in addition to controlling the rate at which the magnesium breaks down, Manuel is trying to determine how much torque can be applied before the screw is stripped. The magnesium pin has been inserted into the tibia of rats, and X-rays show the rate at which the magnesium pins dissolve; at six weeks, the new bone is indistinguishable from the bone before the break.
Another use of the magnesium could be as a coating for an implant to promote bone growth.
“When dealing with resorbable implants there are many challenges to consider, over and above conventional non-absorbable polymeric materials,” Duffy added. “Fundamentally the degradation characteristics of the material needs to be closely managed and controlled. This begins with development of raw material, continues through the entire manufacturing cycle, and is also impacted by sterilization and packaging. Any exposure to heat or moisture can affect the degradation profile, so every process step needs to be considered carefully and managed appropriately. In turn, the implant needs to undergo substantial age testing and characterization to understand how it will be behave in vivo, throughout its functional use and subsequent absorption.”
Resorbability is not the only wonder property creating a foothold in orthopedic devices today. Nitinol has emerged in recent years as a sort of wonder metal with the ability to retain “shape memory” (i.e., nitinol can undergo deformation at one temperature, and then recover its original, undeformed shape upon heating above its transformational temperature). Superelasticity occurs at a narrow temperature range just above its transformation temperature; in this case, no heating is necessary to cause the undeformed shape to recover, and the material exhibits enormous elasticity, some 10-30 times that of ordinary metal. A thermoelastic martensitic phase transformation in the material is responsible for Nitinol’s special properties, which means the atoms that make up the material move together in a homogenous manner in response to some stimulus.
Nitinol is an almost equal-measure alloy of nickel and titanium. While nickel poses some concern regarding allergies and carcinogens, modern methods of electropolishing and passivation have alleviated some of those concerns by forming very effective protective barriers between the metal and its environment. Nitinol’s use in implanted self-expanding stents, such as the Epic Vascular Self-Expanding Stent System from Boston Scientific Corp., has proven successful with no evidence of corrosion or nickel release; and the outcomes in patients with and without nickel allergies are indistinguishable.
In September 2015, a Transparency Market Research report projected the nitinol devices market for final medical components to reach $17.3 billion in 2019. In 2012, this market was valued at $8.2 billion. Fueling this growth is primarily the increasing incidence of various vascular diseases, such as peripheral vascular diseases and coronary artery diseases, but the unique properties of nitinol make it especially well-suited to orthopedic applications. Last year, the U.S. Food and Drug Administration (FDA) cleared a nitinol device from Lexington, Mass.-based MX Orthopedics Corp. intended for fracture and osteotomy fixation of the hand and foot, joint arthrodesis of the hand and foot, and fixation of proximal tibial metaphysis osteotomy. The device—the DynaMX compression staple—combines superelastic legs for compression with a malleable bridge that can be contoured by the surgeon to match the patient’s anatomy for improved functionality and comfort.
Nitinol’s properties have enabled groundbreaking applications in the medical and dental industries. A particularly successful nitinol medical device in the orthopedic space has been the Mitek bone suture anchor made by Depuy Synthes, a Johnson & Johnson Inc. company. According to West Chester, Pa.-based Johnson Matthey Inc. (Johnson Matthey Medical Components), an expert in nitinol components, the Mitek suture anchors have revolutionized the field of orthopedic surgery by providing a secure, stable attachment for tendons, ligaments, and other soft tissue to bone. Consisting of a titanium or nitinol body with two or more arcs of nitinol wire, the Mitek anchor is inserted through a small incision in a hole drilled into the bone. Since its introduction in 1989 for shoulder surgery, use of the Mitek anchor has been expanded to include 25 orthopedic applications and one urological application.
Materials like nitinol fall under the category of smart materials—those that can be significantly changed in a controlled fashion by stimuli such as heat, changes in pH, stress, moisture, or even electric and magnetic fields. A recognizable example is the photochromes in certain eyeglasses that allow them to change to sunglasses in the presence of sunlight. A range of piezoelectric materials, which generate electricity in response to stress, comprises the functional component of ultrasound and echocardiograph probes. Their ability to act as a transducer between voltage and pressure at elevated frequency makes them highly useful for biomedical imaging.
“When you optimize the right material or composite materials, you can significantly improve the performance and reliability of the finished device,” Jens Troetzschel, vice president of advanced technologies for St. Paul, Minn.-based Heraeus Medical Components (Heraeus Deutschland GmbH & Co. KG), told ODT. “And we are seeing some impressive breakthroughs in unlocking the potential of materials. There have been huge steps made in manufacturing technology to produce greater precision and accuracy, for example. Improving materials also enables the industry to raise quality standards, which is a critical requirement for the industry. All of these developments are encouraging, but we aren’t there yet as an industry. But I am confident that we will see continued progress in these areas.”
According to Troetzschel, Heraeus is seeing a trend toward composite and more complex materials that offer superior functionality—for instance, through integrated sensors—better biocompatibility, and increased miniaturization. The company’s newest innovation, CerMet Composites, is an example of where materials science is moving. The composites, which are mixtures of ceramic and metallic materials, offer complete electrical integration, biocompatible hermetic encapsulation, and 3D design functionality in one solution.
“[CerMet] is a game-changer for us, because it is going to enable our device customers to deliver more effective therapy for the patient, greater reliability and safety, and an increased yield in production,” Troetzschel added.
The Plastics World
While metals and ceramics have had a place in the orthopedic device world for decades, plastics have proven to be broadly useful, effective, and even revolutionary in the space since the middle of the 20th century. However, because of their chemical structure, plastics are perennially under the regulatory microscope. The material in all its variations is eminently manufacturable, cheap, durable, and easily manipulated. Therefore, plastics are found in everything from thumbtacks to spaceships—and, of course, medical devices, both external and implantable. Depending on the type of polymer used, the material is also easy to keep sterile; and because plastics can be light and, as mentioned previously, very cheap to produce, they are also the obvious choice for disposable devices.
But a lot goes on under the surface of the various plastics in use in medtech—some examples of which are polyethylene terephthalate (PET), polybutylene terephthalate (PBT), polymethyl methacrylate (PMMA). PMMA, also known as bone cement, is particularly important in orthopedic applications. It is widely used for implant fixation in various orthopedic and trauma surgeries. As noted in a 2013 Journal of Clinical Orthopaedics and Trauma article, “cement” is a misnomer because the word cement is used to describe a substance that bonds two things together. Rather, PMMA acts as a space filler that creates a tight space that holds the implant against the bone and thus acts as a grout. Bone cements have no intrinsic adhesive properties; they rely instead on close mechanical interlock between the irregular bone surface and the prosthesis. Other types of commercially available bone cement like calcium phosphate cements (CPCs) and glass polyalkenoate (ionomer) cements are successfully used in a variety of orthopedic and dental applications. CPCs are bioresorbable and biocompatible, but are mainly used in cranial and maxillo-facial surgeries due to their low mechanical strength.
It was also noted in the article that even though the uses and availability of various types of bone cement has greatly evolved over the past century, further research still continues to develop its more clinical applications and reduces the adverse effects associated with their use. Some risks that have been identified over years of its use are periodical drops in blood pressure, inflammation of vein walls, loosening or displacement of the prosthesis, wound infection, abnormal bone formation, and even short term cardiac conduction irregularities.
“For the treatment of bone fractures, the traditional available technology has been PMMA as a bone cement,” said Scott Mraz, president and chief commercial officer of NuSil Technology LLC, a Carpinteria, Calif.-based silicone materials science company. “We believe there are some advantages to having an elastomeric silicone adhesive that has many of the same attributes of PMMA from an effectiveness perspective in terms of treating bone fractures. But we think there could be some real benefit to having a silicone that is more elastomeric, meaning it has the ability to potentially reduce the incidence of stress fractures associated with traditional bone cement because the mechanical interface of the material is more consistent with the bone material itself. Of course we have a lot of work to do to prove this from a clinical perspective but we’ve done enough work to develop a working hypothesis that we have a lot of conviction around with some good preliminary data.”
NuSil may be changing the game for bone cements. At the end of last year, the company released what it calls the strongest silicone elastomer ever developed. It has a tensile strength of up to 50 percent greater than existing silicone elastomers on the market and a combination of material properties that make it strong but also uniquely soft and pliable. This particular elastomer holds great promise for high performance healthcare applications such as balloon catheters, where the balloon must be easy to inflate, unbreakable, and must deflate fully for ease of removal; but company executives, including Mraz, are working toward expanding the indications for the material as far as possible. These high strength silicones provide design engineers the ability to improve this class of devices by making them thinner, stronger, and more resilient.
“I believe that NuSil’s High Strength Silicone platform is one of the more important innovations in silicone science in the past few decades,” Jim Lambert, Ph.D., NuSil’s director of research and development for Life Sciences, said at the time of the material’s introduction. “I’m truly proud of our development team for pushing the boundaries of what seemed chemically and physically possible, and for delivering products that will enable our customers to innovate beyond the conventional performance limitations of silicone elastomers.”
“As Bill Gates said ‘If you give people tools they will develop things in ways that will surprise you very much beyond what you might have expected,’” Mraz said at the time. “We know the products our customers will develop using this new platform will have the capacity to change lives.”
When discussing plastics, one cannot ignore concerns surrounding toxicity. The FDA as well as European regulators have put plastics, particularly plasticizers—additives used to add fluidity to polymer materials—on the hot seat in recent years for toxicity and leaching concerns.
“In the last two years, we’ve seen a significant increase in the level of biocompatibility and toxicity testing that the FDA has requested on polymer materials, particularly materials that contain colorants,” said Jim Fagan, business development manager for Westlake Plastics Co., an Aston, Pa.-based manufacturer in extrusion and compression molding technologies of high performance thermoplastics. “This is presenting challenges for device manufacturers to complete more rigorous biocompatibility risk assessments, and conduct more testing on their material choices. In turn, the device manufacturers have pushed these requirements and increased demands for testing onto their supply chain. In response to this, we’ve taken a proactive approach with a number of our products, including our Propylux HS colored polypropylene extruded bar stock. This product is used in orthopedic trial components, instruments, and other devices in joint repair and replacement procedures. Each of 11 colors in which the product is offered were individually tested in a fabricated part form to ISO 10993-5, -10 parts 1 and 2, and -11. Performing this testing is helping device manufacturers shorten their product validation cycles and speed their time to market.”
ISO 10993-5 is the international standard for in-vitro cytotoxicity. The test is designed to determine the biological response of mammalian cells exposed in vitro to extracts of the devices. ISO 10993-10 describes the procedure for the assessment of medical devices and their constituent materials with regard to their potential to produce irritation and skin sensitization. ISO 10993-11 gives guidance on procedures to be followed in the evaluation of the potential for medical device materials to cause adverse systemic reactions.
Perhaps the biggest elephant in the room with plastics is the issue of recycling plastic devices, and the environmental consequences of plastics manufacturing. For medical devices, this issue is often not at the forefront of discussions because the relative need and importance of devices in the medical space are high. It is one thing to reprimand populations for using too many plastic bottles or for not disposing of plastic toys correctly; it is another to cause anxiety surrounding the use of plastic medical devices when patients who use them need them to treat a disease or even to survive.
Because disposable devices are so often made of plastic, the issue of recycling for these devices is important. The flip side of that coin is improving the reprocessing of reusable devices, which may be made from plastics or metals. With better reprocessing, not only would hospital-acquired infections be reduced, but the use of reusable devices could increase, allowing for more savings for hospitals that do not have to restock disposables as much.
The FDA's Center for Devices and Radiological Health (CDRH) has made the improvement of reprocessing a priority for 2016. According to the FDA, reusable devices are commonly used in patient care and many reusable devices have evolved into more complex designs, making them more challenging to reprocess. To minimize patient harm from inadequately reprocessed devices and to enhance the safety, effectiveness, performance, and/or quality of these devices, it is critical to develop a comprehensive approach to address the effectiveness of reprocessing techniques. Approaches should encompass the areas of device design, human factors, reprocessing instructions, reprocessing methodologies, validation methods for reprocessing including cleaning and high level disinfection, validated markers of successful reprocessing, and surveillance of reprocessed devices in healthcare facilities.
A Note on 3D Printing
Today, 3D printing technology can handle plastics, metals and ceramics—and universities and research institutions are experimenting with various live-tissue 3D printing. Most often, 3D printing (also known as additive manufacturing) is used for prototyping medical devices, and plastics are often used for mockups because they are cheap and lightweight. Direct metal laser sintering (DMLS), on the other hand, has been in use for over two decades in the medical device industry. Munich, Germany-based EOS Gmbh, for instance, provides an entire line of DMLS machines that can create the complex metal medical components and devices through additive manufacturing.
The classic quibble, though, is large-scale production. While 3D printing is fast and cost effective, it does not have the same volume capabilities that other manufacturing processes do.
“3D manufacturing provides obvious advantages for tooling and product prototyping, reducing development costs and timelines,” Proxy Biomedical’s Duffy said. “I also believe it offers potential for development of unique structures, such as scaffolds with a custom porosity to support the bioactive growth factors. However, it remains to be seen whether this process will be widely adopted for volume manufacturing down the line.”
“It’s exciting to see how the process technology and material options have exploded in the last few years,” said Fagan. “I think 3D printing will continue to be a great tool for rapid prototyping of complex functional parts that can accelerate the component validation process. I think it will also be a useful means for producing customized ‘one-off’ designs. However, I am more skeptical about its ability to be a cost-effective production method for fully functional devices that need to be produced in larger quantities.”
These materials do not offer the same strength capabilities titanium implants might, for instance, but their purpose is not to remain in permanent implantation. While in place, however, resorbable implants should be able to provide the required level of strength, rigidity, and/or flexibility, depending on the application.
“There is a definite shift towards the use of resorbable implants, wherever possible, and sophisticated processing methods are achieving more with existing materials,” Stephen Duffy, business development manager for Proxy Biomedical Ltd., told Orthopedic Design & Technology. “Proxy Biomedical has developed Bio-XT processing technology to reinforce resorbable implants, including composite materials that are loaded with ceramics. This technology is presenting opportunities in next-generation implant design, from lower profile implants to more porous designs and stronger implants with the potential to address load bearing indications. By using existing materials with an established clinical history, the regulatory burden is reduced and speed to market improved. I expect that we will see the proliferation of absorbable implants, with the benefit of technologies such as this, as well as greater use of bioactive materials.”
In 2014, researchers at the University of Florida developed magnesium as a possible alternative for metal implants that could be resorbable as well as strong enough to provide adequate support while in use. The pin developed by Michele Manuel, associate professor of materials science and engineering at the university, not only breaks down but also aids healing.
“We don’t always want to put in a metal implant and leave it there forever,” Manuel said. “The idea with this pin is that it would dissolve over time, and after it’s finished, your body is basically in the same state it was before you had an injury. Everybody knows someone who has an implant in their body that they wish wasn’t there,” Manuel said. “Surgical pins don’t have to become permanent fixtures in the body. Magnesium builds bone, so it can function both as a pin and as a nutrient. You have to have magnesium to live, and many people take magnesium supplements, so this is a good orthopedic application. It’s not only an implant that serves a medical need in terms of fixing bones, it’s also serving a nutritional need as well, so that’s why you see a lot of activity in the surrounding tissue.”
The use of magnesium isn’t new, Manuel said. In the early 1800s, physicians experimented with magnesium implants but ran into problems because magnesium produces hydrogen as it breaks down, which creates hydrogen gas bubbles under the skin that are clearly visible. Physicians of the era tried to remove the hydrogen gas with syringes but eventually gave up until new, improved metals were developed.
The trick to using magnesium, Manuel said, is controlling the rate at which it breaks down to give the body time to absorb the hydrogen.
“Your body can handle the hydrogen, just not in large doses, so pockets form,” Manuel said. “So if we can slow down how fast the magnesium degrades so it releases hydrogen more slowly, the body would take up the hydrogen the way it would take up any other gas and release it.”
In lab tests, Manuel has compared the magnesium pin with clinical implant materials. Surgical pins are shaped like screws, so in addition to controlling the rate at which the magnesium breaks down, Manuel is trying to determine how much torque can be applied before the screw is stripped. The magnesium pin has been inserted into the tibia of rats, and X-rays show the rate at which the magnesium pins dissolve; at six weeks, the new bone is indistinguishable from the bone before the break.
Another use of the magnesium could be as a coating for an implant to promote bone growth.
“When dealing with resorbable implants there are many challenges to consider, over and above conventional non-absorbable polymeric materials,” Duffy added. “Fundamentally the degradation characteristics of the material needs to be closely managed and controlled. This begins with development of raw material, continues through the entire manufacturing cycle, and is also impacted by sterilization and packaging. Any exposure to heat or moisture can affect the degradation profile, so every process step needs to be considered carefully and managed appropriately. In turn, the implant needs to undergo substantial age testing and characterization to understand how it will be behave in vivo, throughout its functional use and subsequent absorption.”
Resorbability is not the only wonder property creating a foothold in orthopedic devices today. Nitinol has emerged in recent years as a sort of wonder metal with the ability to retain “shape memory” (i.e., nitinol can undergo deformation at one temperature, and then recover its original, undeformed shape upon heating above its transformational temperature). Superelasticity occurs at a narrow temperature range just above its transformation temperature; in this case, no heating is necessary to cause the undeformed shape to recover, and the material exhibits enormous elasticity, some 10-30 times that of ordinary metal. A thermoelastic martensitic phase transformation in the material is responsible for Nitinol’s special properties, which means the atoms that make up the material move together in a homogenous manner in response to some stimulus.
Nitinol is an almost equal-measure alloy of nickel and titanium. While nickel poses some concern regarding allergies and carcinogens, modern methods of electropolishing and passivation have alleviated some of those concerns by forming very effective protective barriers between the metal and its environment. Nitinol’s use in implanted self-expanding stents, such as the Epic Vascular Self-Expanding Stent System from Boston Scientific Corp., has proven successful with no evidence of corrosion or nickel release; and the outcomes in patients with and without nickel allergies are indistinguishable.
In September 2015, a Transparency Market Research report projected the nitinol devices market for final medical components to reach $17.3 billion in 2019. In 2012, this market was valued at $8.2 billion. Fueling this growth is primarily the increasing incidence of various vascular diseases, such as peripheral vascular diseases and coronary artery diseases, but the unique properties of nitinol make it especially well-suited to orthopedic applications. Last year, the U.S. Food and Drug Administration (FDA) cleared a nitinol device from Lexington, Mass.-based MX Orthopedics Corp. intended for fracture and osteotomy fixation of the hand and foot, joint arthrodesis of the hand and foot, and fixation of proximal tibial metaphysis osteotomy. The device—the DynaMX compression staple—combines superelastic legs for compression with a malleable bridge that can be contoured by the surgeon to match the patient’s anatomy for improved functionality and comfort.
Nitinol’s properties have enabled groundbreaking applications in the medical and dental industries. A particularly successful nitinol medical device in the orthopedic space has been the Mitek bone suture anchor made by Depuy Synthes, a Johnson & Johnson Inc. company. According to West Chester, Pa.-based Johnson Matthey Inc. (Johnson Matthey Medical Components), an expert in nitinol components, the Mitek suture anchors have revolutionized the field of orthopedic surgery by providing a secure, stable attachment for tendons, ligaments, and other soft tissue to bone. Consisting of a titanium or nitinol body with two or more arcs of nitinol wire, the Mitek anchor is inserted through a small incision in a hole drilled into the bone. Since its introduction in 1989 for shoulder surgery, use of the Mitek anchor has been expanded to include 25 orthopedic applications and one urological application.
Materials like nitinol fall under the category of smart materials—those that can be significantly changed in a controlled fashion by stimuli such as heat, changes in pH, stress, moisture, or even electric and magnetic fields. A recognizable example is the photochromes in certain eyeglasses that allow them to change to sunglasses in the presence of sunlight. A range of piezoelectric materials, which generate electricity in response to stress, comprises the functional component of ultrasound and echocardiograph probes. Their ability to act as a transducer between voltage and pressure at elevated frequency makes them highly useful for biomedical imaging.
“When you optimize the right material or composite materials, you can significantly improve the performance and reliability of the finished device,” Jens Troetzschel, vice president of advanced technologies for St. Paul, Minn.-based Heraeus Medical Components (Heraeus Deutschland GmbH & Co. KG), told ODT. “And we are seeing some impressive breakthroughs in unlocking the potential of materials. There have been huge steps made in manufacturing technology to produce greater precision and accuracy, for example. Improving materials also enables the industry to raise quality standards, which is a critical requirement for the industry. All of these developments are encouraging, but we aren’t there yet as an industry. But I am confident that we will see continued progress in these areas.”
According to Troetzschel, Heraeus is seeing a trend toward composite and more complex materials that offer superior functionality—for instance, through integrated sensors—better biocompatibility, and increased miniaturization. The company’s newest innovation, CerMet Composites, is an example of where materials science is moving. The composites, which are mixtures of ceramic and metallic materials, offer complete electrical integration, biocompatible hermetic encapsulation, and 3D design functionality in one solution.
“[CerMet] is a game-changer for us, because it is going to enable our device customers to deliver more effective therapy for the patient, greater reliability and safety, and an increased yield in production,” Troetzschel added.
The Plastics World
While metals and ceramics have had a place in the orthopedic device world for decades, plastics have proven to be broadly useful, effective, and even revolutionary in the space since the middle of the 20th century. However, because of their chemical structure, plastics are perennially under the regulatory microscope. The material in all its variations is eminently manufacturable, cheap, durable, and easily manipulated. Therefore, plastics are found in everything from thumbtacks to spaceships—and, of course, medical devices, both external and implantable. Depending on the type of polymer used, the material is also easy to keep sterile; and because plastics can be light and, as mentioned previously, very cheap to produce, they are also the obvious choice for disposable devices.
But a lot goes on under the surface of the various plastics in use in medtech—some examples of which are polyethylene terephthalate (PET), polybutylene terephthalate (PBT), polymethyl methacrylate (PMMA). PMMA, also known as bone cement, is particularly important in orthopedic applications. It is widely used for implant fixation in various orthopedic and trauma surgeries. As noted in a 2013 Journal of Clinical Orthopaedics and Trauma article, “cement” is a misnomer because the word cement is used to describe a substance that bonds two things together. Rather, PMMA acts as a space filler that creates a tight space that holds the implant against the bone and thus acts as a grout. Bone cements have no intrinsic adhesive properties; they rely instead on close mechanical interlock between the irregular bone surface and the prosthesis. Other types of commercially available bone cement like calcium phosphate cements (CPCs) and glass polyalkenoate (ionomer) cements are successfully used in a variety of orthopedic and dental applications. CPCs are bioresorbable and biocompatible, but are mainly used in cranial and maxillo-facial surgeries due to their low mechanical strength.
It was also noted in the article that even though the uses and availability of various types of bone cement has greatly evolved over the past century, further research still continues to develop its more clinical applications and reduces the adverse effects associated with their use. Some risks that have been identified over years of its use are periodical drops in blood pressure, inflammation of vein walls, loosening or displacement of the prosthesis, wound infection, abnormal bone formation, and even short term cardiac conduction irregularities.
“For the treatment of bone fractures, the traditional available technology has been PMMA as a bone cement,” said Scott Mraz, president and chief commercial officer of NuSil Technology LLC, a Carpinteria, Calif.-based silicone materials science company. “We believe there are some advantages to having an elastomeric silicone adhesive that has many of the same attributes of PMMA from an effectiveness perspective in terms of treating bone fractures. But we think there could be some real benefit to having a silicone that is more elastomeric, meaning it has the ability to potentially reduce the incidence of stress fractures associated with traditional bone cement because the mechanical interface of the material is more consistent with the bone material itself. Of course we have a lot of work to do to prove this from a clinical perspective but we’ve done enough work to develop a working hypothesis that we have a lot of conviction around with some good preliminary data.”
NuSil may be changing the game for bone cements. At the end of last year, the company released what it calls the strongest silicone elastomer ever developed. It has a tensile strength of up to 50 percent greater than existing silicone elastomers on the market and a combination of material properties that make it strong but also uniquely soft and pliable. This particular elastomer holds great promise for high performance healthcare applications such as balloon catheters, where the balloon must be easy to inflate, unbreakable, and must deflate fully for ease of removal; but company executives, including Mraz, are working toward expanding the indications for the material as far as possible. These high strength silicones provide design engineers the ability to improve this class of devices by making them thinner, stronger, and more resilient.
“I believe that NuSil’s High Strength Silicone platform is one of the more important innovations in silicone science in the past few decades,” Jim Lambert, Ph.D., NuSil’s director of research and development for Life Sciences, said at the time of the material’s introduction. “I’m truly proud of our development team for pushing the boundaries of what seemed chemically and physically possible, and for delivering products that will enable our customers to innovate beyond the conventional performance limitations of silicone elastomers.”
“As Bill Gates said ‘If you give people tools they will develop things in ways that will surprise you very much beyond what you might have expected,’” Mraz said at the time. “We know the products our customers will develop using this new platform will have the capacity to change lives.”
When discussing plastics, one cannot ignore concerns surrounding toxicity. The FDA as well as European regulators have put plastics, particularly plasticizers—additives used to add fluidity to polymer materials—on the hot seat in recent years for toxicity and leaching concerns.
“In the last two years, we’ve seen a significant increase in the level of biocompatibility and toxicity testing that the FDA has requested on polymer materials, particularly materials that contain colorants,” said Jim Fagan, business development manager for Westlake Plastics Co., an Aston, Pa.-based manufacturer in extrusion and compression molding technologies of high performance thermoplastics. “This is presenting challenges for device manufacturers to complete more rigorous biocompatibility risk assessments, and conduct more testing on their material choices. In turn, the device manufacturers have pushed these requirements and increased demands for testing onto their supply chain. In response to this, we’ve taken a proactive approach with a number of our products, including our Propylux HS colored polypropylene extruded bar stock. This product is used in orthopedic trial components, instruments, and other devices in joint repair and replacement procedures. Each of 11 colors in which the product is offered were individually tested in a fabricated part form to ISO 10993-5, -10 parts 1 and 2, and -11. Performing this testing is helping device manufacturers shorten their product validation cycles and speed their time to market.”
ISO 10993-5 is the international standard for in-vitro cytotoxicity. The test is designed to determine the biological response of mammalian cells exposed in vitro to extracts of the devices. ISO 10993-10 describes the procedure for the assessment of medical devices and their constituent materials with regard to their potential to produce irritation and skin sensitization. ISO 10993-11 gives guidance on procedures to be followed in the evaluation of the potential for medical device materials to cause adverse systemic reactions.
Perhaps the biggest elephant in the room with plastics is the issue of recycling plastic devices, and the environmental consequences of plastics manufacturing. For medical devices, this issue is often not at the forefront of discussions because the relative need and importance of devices in the medical space are high. It is one thing to reprimand populations for using too many plastic bottles or for not disposing of plastic toys correctly; it is another to cause anxiety surrounding the use of plastic medical devices when patients who use them need them to treat a disease or even to survive.
Because disposable devices are so often made of plastic, the issue of recycling for these devices is important. The flip side of that coin is improving the reprocessing of reusable devices, which may be made from plastics or metals. With better reprocessing, not only would hospital-acquired infections be reduced, but the use of reusable devices could increase, allowing for more savings for hospitals that do not have to restock disposables as much.
The FDA's Center for Devices and Radiological Health (CDRH) has made the improvement of reprocessing a priority for 2016. According to the FDA, reusable devices are commonly used in patient care and many reusable devices have evolved into more complex designs, making them more challenging to reprocess. To minimize patient harm from inadequately reprocessed devices and to enhance the safety, effectiveness, performance, and/or quality of these devices, it is critical to develop a comprehensive approach to address the effectiveness of reprocessing techniques. Approaches should encompass the areas of device design, human factors, reprocessing instructions, reprocessing methodologies, validation methods for reprocessing including cleaning and high level disinfection, validated markers of successful reprocessing, and surveillance of reprocessed devices in healthcare facilities.
A Note on 3D Printing
Today, 3D printing technology can handle plastics, metals and ceramics—and universities and research institutions are experimenting with various live-tissue 3D printing. Most often, 3D printing (also known as additive manufacturing) is used for prototyping medical devices, and plastics are often used for mockups because they are cheap and lightweight. Direct metal laser sintering (DMLS), on the other hand, has been in use for over two decades in the medical device industry. Munich, Germany-based EOS Gmbh, for instance, provides an entire line of DMLS machines that can create the complex metal medical components and devices through additive manufacturing.
The classic quibble, though, is large-scale production. While 3D printing is fast and cost effective, it does not have the same volume capabilities that other manufacturing processes do.
“3D manufacturing provides obvious advantages for tooling and product prototyping, reducing development costs and timelines,” Proxy Biomedical’s Duffy said. “I also believe it offers potential for development of unique structures, such as scaffolds with a custom porosity to support the bioactive growth factors. However, it remains to be seen whether this process will be widely adopted for volume manufacturing down the line.”
“It’s exciting to see how the process technology and material options have exploded in the last few years,” said Fagan. “I think 3D printing will continue to be a great tool for rapid prototyping of complex functional parts that can accelerate the component validation process. I think it will also be a useful means for producing customized ‘one-off’ designs. However, I am more skeptical about its ability to be a cost-effective production method for fully functional devices that need to be produced in larger quantities.”