Originally Published MPMN
Special feature: EMERGING TECHnologies
Materials Research Gets Under the Skin
Scientists push biocompatible materials to interact with their surroundings in intelligent ways
Current research and development efforts are expanding the scope of what materials can do for medical devices. Beyond serving as foundations for creating devices, materials are increasingly functioning as components that enhance device capabilities. Emerging technologies at the university level, as well as developments from industry, are demonstrating advances in controlling how materials interact with each other and their environments.
Short-term trends in materials development and use are being driven primarily by problems experienced by devices in the clinical environment. Long-term developments, however, are looking at new technologies that cooperate with the human body to restore or improve function, according to Jeremy Gilbert, biomaterials professor at Syracuse University
(Syracuse, NY; www.syr.edu
) and founder of the university’s Biomaterials Institute. To further explore these trends with members of industry, Gilbert will be chairing the Conference on Materials and Processes for Medical Devices, organized by ASM International
(Materials Park, OH; www.asminternational.org
), which will be held August 10–12 in Minneapolis.
Of the short-term developments, orthopedic applications, for example, are focused on ways to increase wear and corrosion resistance. Not limited to device surfaces, research for orthopedics is also investigating improving infection control using localized drug delivery, Gilbert says. Of particular note is the increasing prevalence of cardiac, orthopedic, neurological, and visual disorders combined with ongoing improvements in the safety and effectiveness of devices. In light of these factors, market research firm The Freedonia Group
) expects that demand for implantable devices will increase 7.7% annually to $40.2 billion in 2011.
Long-term materials trends are mostly related to the development of tissue-engineered devices, combination products, and smart medical devices, Gilbert says. “In the case of smart medical devices, people are looking at ways to have materials interact with the body in intelligent ways, such as sensing their surroundings, communicating, and responding to specific stimuli,” he adds.
The following articles in this feature highlight new developments in materials that reflect these trends.
Mining Gold for Targeted Drug Delivery
Drugs attached to the surface of these gold nanoparticles dissolve after exposure to a specific infrared light frequency, enabling targeted drug delivery.
Working to develop smarter devices, researchers at Massachusetts Institute of Technology
(Cambridge, MA; www.mit.edu
) are using gold to control drug delivery by external means rather than having to program timed-release capabilities into the device.
“Currently, programming release from drug carriers is achieved by controlling the rate at which a drug leaks from the carrier, usually by modifying the chemical properties of a polymer,” explains Kimberly Hamad-Schifferli, assistant professor in the departments of mechanical and biological engineering. Such passive drug-delivery methods require a great deal of effort to achieve a constant rate of release without bursting out all at once, she says.
Compared with the current drug-leaking release technologies, external control methods could enable precise execution of timed release, as well as coordinating the timed release of multiple drugs. To demonstrate these methods, Hamad-Schifferli and her team employed gold nanoparticles, which melt and release the drug payloads attached to them when they are exposed to specific frequencies of infrared light. Because different shapes of the gold nanoparticles react to different infrared wavelengths, various drugs can be attached to the nanoparticles and then released upon exposure to the correct infrared light.
“We chose gold due to the fact that you can change its absorbing wavelength by changing its shape and size,” she says. “Also, gold is easy to link molecules like drugs and DNA to.” She adds that there are probably other inorganic and organic materials that can be covalently linked to drugs and excited by infrared light using an infrared dye; however, only gold nanorods have shape-tunable infrared spectra. This feature is what enables the gold to be used for delivering multiple drugs. More-controlled release of multiple drugs could potentially enable better treatment of diseases that involve drugs working in combination, such as various cancers and HIV/AIDS.
The team could potentially develop up to four different particle shapes that are each capable of releasing different drug payloads when exposed to their corresponding wavelengths. For its current research, the team has experimented with two shapes of nanoparticles: nanobones, which melt at light wavelengths of 1100 nm, and nanocapsules, which melt at 800 nm.
“In theory, one could put almost any biological molecule or drug on the nanorods, so this technology could be applied to externally control any biological process,” Hamad-Schifferli says. “It could be used to release species that stop blood clotting or induce wound healing.”
Glass-Fiber Biomaterial Designed for Long-Term Implants
HPB glass-fiber biomaterial is suitable for use in long-term implant applications and is compatible with a range of thermoplastic polymers.
In response to increasing demand for high-performance biocompatible composite materials, AGY
(Aiken, SC; www.agy.com
), a supplier of high-strength glass-fiber yarns, has specifically engineered a glass-fiber biomaterial for long-term implant applications. Such applications could include knee and hip replacement devices, spinal cages, and dental and orthodontic products.
“Currently, the long-term implantable market has very few material options that designers can use for creating medical devices,” says Drew Walker, vice president of sales and marketing. “AGY saw the opportunity to develop a biomaterial that could work in conjunction with high-performance engineering thermoplastics and compete with ceramics, titanium, and other more-traditional implant materials.”
Compatible with a range of thermoplastic polymers, including PEEK, PEI, and PPS, the material can be tailored to meet customers’ specific application requirements. For injection molding applications, combining the high-performance biomaterial (HPB) glass fiber with such polymers can result in a higher degree of impact performance as compared with materials such as ceramics, according to Walker. This capability is important to designers who want to create the same modulus with thermoplastic materials as is found in bone, he says. “The advantages are both aesthetic- and performance-related.”
Part of the company’s S-3 glass-fiber family of special-grade products, the HPB material exhibits tensile strength and resistance to creep and elasticity that make it suitable for long-term implant applications. It has a 40% higher tensile strength and 20% higher tensile modulus than that of standard E-glass fibers currently available, according to the company.
“[The high tensile strength] helps create new injection-molded shapes that are lighter, have better impact properties, and are stiffer and stronger,” Walker says.
The combination of such features as biocompatibility and strength, in addition to cost-effectiveness, makes the glass fiber a promising alternative to a variety of materials, including ceramic-metal composites, he adds.
Using proprietary glass-processing technology, the company can provide the material in a range of yarn, chopped, pellet, and roving formats. Roving formats can allow for easier integration into automated processes, such as mixing.
Silk Solution Created for Implantable, Optical Applications
After extracting sericin from silkworm cocoons to make the material biocompatible, a silk fibroin solution can be used to make biosensor and optical device components.
Photo Credit: Fiorenzo Omenetto (Tufts University)
Although medical device applications such as surgical wires have incorporated natural silk, they required a coating in order to prevent adverse reactions to the sericin in the material. A glycoprotein in silk responsible for holding cocoons together, sericin is good for silkworms, but can cause reactions such as inflammation in humans.
To address this issue, David Kaplan, professor of biomedical engineering (BME) at Tufts University
(Medford, MA; www.tufts.edu
) has developed a method for extracting sericin from silk so that it becomes a truly biocompatible substance. Employing this process, Fiorenzo Omenetto, also a BME professor at Tufts, can produce a purified protein silk fibroin solution, which can then be used to make implantable components for biosensor and optical applications.
The sericin-extraction process involves boiling the cocoon in a solution containing salt sodium carbonate—after removing the silkworm from the cocoon, of course. Salt sodium carbonate dissolves the sericin and, after drying, the silk fibers are then dissolved in a solution of lithium bromide. After cooling, the dissolved fibers are loaded into a dialysis cartridge, which is set inside of a beaker to draw out salt. The remaining material in the cartridge is the water-based purified silk fibroin solution, which can be used to make optical device components.
The material rivals the strength of glass and plastic currently used in optical devices. “This material has surprisingly good optical quality,” Omenetto explains. “The added value of using silk instead of a polycarbonate or glass is that it is biocompatible and potentially edible.”
Additionally, Omenetto can mix a protein into the viscous silk solution to target specific molecules as a function of a biosensor, for example. Because the silk is processed at room temperature and does not require harsh chemicals, the environment is conducive to mixing the silk solution with biological molecules used in biosensor applications. “In hardened form, the biochemical activity of the proteins previously mixed in the silk solution is preserved,” he says. Potentially, such immobilized components of the solution could be used for implantable biosensor applications.
Although this technology is still being developed, Omenetto says that it’s not too futuristic. He anticipates that the technology could be available within a few years.
Metallic-Glass Composites: Tough as Steel, Light as Titanium
Large ingots of a new titanium-based metallic glass composite surrounded by cast parts of commercially available liquid metal. Unlike the cast parts, which are made primarily from zirconium and are brittle, the new titanium composites have high ductility and low density. This makes the new alloys suitable for many small-part applications.
Photo Credit: Douglas Hofmann (Caltech)
Scientists at California Institute of Technology
(Caltech; Pasadena, CA; www.caltech.edu
) have created titanium-based metallic-glass composite materials that can be molded at about half the temperature as traditional titanium alloys but offer the mechanical properties of steel. Designed as an alternative material for applications reliant on the crystalline structure and performance characteristics of titanium, these composite materials could potentially be used for such implantables as hip-replacement devices. They could also be used to make structural parts such as wires, pins, and screws for internal use.
Featuring a higher ratio of titanium to zirconium than previous metallic-glass composites created by the Caltech team, these alloys offer tension ductility greater than 10%. They also provide a yield strength above 1.4 gigapascals, which is comparable to high-strength steels, according to Douglas Hofmann, visiting scientist at Caltech’s department of materials science. From research for other applications, Hofmann and his colleagues have become familiar with the brittle nature of single-phase metallic-glass materials. Unlike the single-phase glasses, these titanium-based composites are made using a two-phase glass, which enables the materials to bend. They also provide fracture toughness and fatigue limits similar to steel, but with much lower densities. High-strength steels typically have volume densities of approximately 8 g/cm³, whereas crystalline titanium alloys have densities ranging between 4.5 and 5 g/cm³.
But among the most significant benefits is the reduced temperature at which the composites can be molded. To mold titanium, most applications require that manufacturers cast a sacrificial mold of liquid titanium—a process that can be costly. And if manufacturers are machining titanium parts, the cost to cut the parts to shape can be more than the cost of the material, especially with something like a hip ball joint, Hofmann says. The high ductility and low processing temperatures of the metallic-glass composites make them less expensive and easier to incorporate into manufacturing processes. Moreover, they can be processed with reusable molds, rather than requiring a sacrificial mold.
Processing benefits haven’t been the only focus of the research, however. One of the biggest challenges Hofmann’s group has encountered in creating this line of composite materials has been biocompatibility. Considering potential applications for both the aerospace and medical markets, the group is experimenting with several elements that can work in the metallic-glass composites. Some versions containing nickel and copper would be toxic to the human body; however, those components could be replaced by an element such as cobalt to make the material biocompatible. The commercial arm of this project, Liquidmetal Technologies
(Rancho Santa Margarita, CA; www.liquidmetal.com
), for which Hofmann is a research and development scientist, is equipped to work with OEMs to create custom biocompatible versions of the composite materials.
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