Michael Barbella09.16.14
“...in a lot of cases it’s seeing two things and having them come together in some new and interesting way, and then adding the question, ‘What if?’ ‘What if?’ is always the key question.”
It began, as most great ideas do, with a simple query.
For days, or maybe weeks back in 2012 (the memory is now a blur), Jay F. Whitacre pondered the feasibility of supersized batteries. Is it possible, he wondered, to make such large-scale devices?
Whitacre wracked his brain for answers but continually came up empty. Thinking about it, in fact, only led to more questions: Are there size limitations to batteries? Could they be made as big as a car or garage? A house? How difficult would it be to make a mega-battery? What would it cost? Are they even practical?
Lots of unanswered questions. And no Eureka! moment.
The proverbial “aha!” lightbulb eventually flickered in the hallowed fourth-floor corridor of Carnegie Mellon University’s Wean Hall. The building’s north wing houses Whitacre’s office and those of several other Materials Science and Engineering faculty, including Christopher J. Bettinger, Ph.D., director of CMU’s Biomaterials-based Microsystems and Electronics laboratory.
Whitacre quickly found a confidante in Bettinger upon his arrival at CMU two years ago. Connected by fate (their offices sit only four rooms apart), the pair quickly forged a friendship based on common interests: Both men hold doctorate degrees in materials science; both teach materials science and engineering courses at CMU (Bettinger also is a biomedical engineering instructor); and both spawned companies from their scientific passions (Whitacre’s Aquion Energy develops sodium ion batteries and energy storage systems while Bettinger’s AnCure designs brain aneurysm treatment devices).
As CMU neighbors, Whitacre and Bettinger often discussed their work and respective research. It was one of those conversations that led to an epiphany about batteries, though it was radically different from anything Whitacre had previously considered.
“Because we work in close proximity, we’ve thought about this [battery] idea a lot,” explained Bettinger, recipient of the National Academy of Sciences Award for Initiatives in Research. “He [Whitacre] develops batteries for large-scale energy storage. Rather than use expensive materials to build batteries, his idea is to use a simple, inexpensive material. It turns out that using aqueous electrolytes, or salt water-based electrolytes, are pretty important in moving ions around. Our bodies are made up of mostly salt water, so we started asking ‘what if?’ What if we used aqueous electrolytes from the body as a component of this battery? That could be interesting.”
Not exactly an Archimedes-like breakthrough for Whitacre’s big battery brainstorm, but a Eureka! moment nonetheless. The lightbulb was on.
And shining brightly on the opposite end of the battery size spectrum. Human electrolytes may not be practicable for supersized batteries but they’re an ideal power source for miniscule electronic devices. Making these batteries suitable for implantation inside the body, however, has proved challenging.
Most energy storage systems that power automated medical devices use potentially toxic electrode materials and electrolytes that compromise their safety. To become eligible for implantation, these storage systems must be composed of benign materials and able to operate in hydrated environments.
Last spring, Bettinger and Whitacre created edible power sources for medical devices using materials found in a daily diet. Their initial design involved a flexible polymer electrode and a sodium ion electrochemical cell that was folded into an edible pill encapsulating the tiny device.
Since then, the pair has improved upon their original design by using cuttlefish ink melanins. The naturally occurring melanins (pigment) in the mollusk’s ink have a higher charge storage capacity compared to other synthetic melanin derivatives when used as anode materials. And pigment-based anodes are an essential component of sodium-ion batteries, the technology Whitacre has pioneered through his company.
“We discovered that melanin—the pigment in your eyes, your skin and your hair—has an interesting cross-section of properties that make it ideal for powering an ingestible electronic device. One of the more interesting aspects of melanin is the nanoscale structures that occur naturally,” Bettinger told Orthopedic Design & Technology. “This nanoscale structure found in nature is very similar to the structure you might find in a battery that powers your cell phone or laptop. There’s a consequential structural conformity between melanins and high-performance batteries. We took that idea and ran with it, using melanin to make batteries that could power edible electronic devices in the future.”
Ingestible electronics, nanobiomaterials, microscopic sensors and tiny biomimetic scaffolds are just a few of the probable treatment options in that future as nanotechnology further ingrains itself in the medical device and pharmaceutical industries. Industry experts predict the global nanomedicine market to achieve a compound annual growth rate of 12.3 percent through 2019, reaching a net worth of $177.6 billion, according to Transparency Market research statistics.
‘Transformational’ Technology
Nanotechnology, in its most basic form, is the study, production and manipulation of matter at the atomic/molecular level (less than 100 nanometers). The concept was first proposed 55 years ago by theoretical physicist Richard P. Feynman during a lecture to the American Physical Society. In his speech—now considered a seminal event in nanotech’s relatively short history—Feynman laid the conceptual foundation for small-scale physics, envisioning a world of dense computer circuitry, extremely powerful electron microscopes, and swallowable surgeons. He conceived such prognostic notions by asking the same simple question that has spawned countless other Eureka! moments throughout the ages: What if?
“It is a staggeringly small world that is below,” Feynman said in his 1959 lecture, aptly titled, “There is Plenty of Room at the Bottom.” “I am not afraid to consider the final question as to whether, ultimately—in the great future—we can arrange the atoms the way we want; the very atoms, all the way down! What would happen if we could arrange the atoms one by one the way we want them (within reason, of course...)?”
Here’s what happens: Those atoms abide by the laws of quantum mechanics, affecting the optical, electrical and magnetic behaviors of a material. Also, surface area to volume ratio skyrockets, drastically altering the properties of a nanostructure and triggering some very unconventional conduct. Opaque substances such as copper, for example, become transparent, while inert elements become catalysts (platinum); stable materials turn combustible (aluminum), golds and other solids morph into liquids (at room temperature), and insulators become conductors (silicon).
In the nanotech world, all bets indeed are off.
Yet it is those anomalies—particularly the significantly higher surface area associated with nanomaterials—that hold so much promise for the orthopedic device industry. Research has shown higher surface area can bolster the interaction between implants and host bone, improving osseointegration by promoting both differentiation of mesenchymal stromal cells and the adsorption of extracellular adhesion molecules necessary for osteoblast function.
“Nanoscience is making its way into many key areas of orthopedics, including in clinical practice,” Nicola Baldini, an orthopedic surgeon and associate professor of orthopedics at the University of Bologna, Italy, said at the 15th EFORT Congress in London, United Kingdom, in June. Baldini also is a visiting professor at Kyoto Prefectural University of Medicine in Kyoto, Japan, and head of the Laboratory for Orthopedic Pathophysiology and Regenerative Medicine.
“Research into therapies that involve the manipulation of individual genes or the molecular pathways that influence their expression is on the rise,” he noted. “Nanotechnology holds enormous potential for orthopedics.”
The magnitude of that potential clearly is evident, too, in the various applications now underway: Silver nanoparticles, for instance, are being used to prevent infections, while nanocomposite scaffolds show promise in repairing osteochondral knee defects and nanofibers are proving an effective alternative to thick, stiff surgical mesh.
Smith & Nephew plc is a virtual pioneer in the nanotech world, having released a nanocrystalline antimicrobial burn dressing back in 1998. The nanocrystals in the firm’s Acticoat product line release silver ions in the dressing and sustain release for up to seven days, killing such virulent germs as MRSA (methicillin-resistant Staphylococcus aureus) and VRE (vancomycin resistant enteroccocus).
AcryMed Inc.’s SilvaGard also is a microbial murderer, but it masquerades as an implant coating.
SilvaGard-treated devices are immersed in a liquid solution of silver nanoparticles, coating all exposed surfaces with the antimicrobial agent. The Beaverton, Ore.-based company contends its technology can resist germs for “days, weeks or months” depending upon the device application. The period of efficacy can be varied by changing the amount of silver applied to the product during treatment, thus allowing device manufacturers to customize the process to best meet specific requirements. The U.S. Food and Drug Administration (FDA) approved AcryMed’s SilvaGard technology in 2005, allowing I-Flow Corporation to market its ON-Q Silver Soaker regional anesthesia delivery catheters.
Matthew MacEwan is hoping to gain the FDA’s blessing for a synthetic polymer surgical mesh made from individual strands of nanofibers. Initially developed by his startup firm NanoMed LLC to treat brain and spinal cord injuries, the mesh also could be used to mend hernias, fistulas and other wounds.
Existing surgical mesh used to repair the protective membrane covering the brain and spinal cord typically is derived from pig or cow skin, making it thick, stiff and difficult to work with. The material MacEwan developed with Jingwei Xie, Ph.D., and two other Washington University (St. Louis, Mo.) scholars is thin, flexible and more likely to integrate with the body’s own tissues.
“It’s almost like a cloth,” said MacEwan, who also is perfecting a surgical mesh for neurosurgical procedures. “But it’s designed on a nanoscopic scale. To put that into perspective, every thread of the mesh is thousands of times smaller than the diameter of a single cell.”
Resembling gauze, the sticky DuraStar Dural Substitute is composed of multiple layers of nanofibers and can be custom-sized for different uses. When implanted, cells grow alongside the mesh’s individual nanofibers; the mesh gradually degrades in nine to 12 months, leaving the body’s own tissue in place.
“We’ve taken the whole idea of surgical mesh and pushed it into a new direction,” MacEwan told a Washington University reporter. “It’s not just a foreign material you’re putting into the body. The nanofabricated nature of the mesh creates a scaffold that cells can easily penetrate and populate to recapitulate the body’s tissues.”
Nanofiber scaffolds also play a key role in speculative new rotator cuff repair treatment. Using a $293,000 National Institutes of Health grant, researchers from Marshall University in West Virginia are working on a way to replicate Mother Nature’s tendon-shoulder bone attachment. Their initial design combines a nanofiber scaffold with adipose-derived stem cells to promote tissue repair after rotator cuff surgery, one of the most common orthopedic procedures in the United States (roughly 300,000 are performed annually, according to industry statistics).
Current rotator cuff repair methods have a failure rate that ranges between 20 percent and 90 percent, due largely to the manner in which tendons are reattached to the bone. Marshall University researchers have found that controlling the mineralization of electrospun nanofibers greatly enhances their mechanical properties (i.e., stiffness, ultimate tensile strength and toughness), creating scaffolds with gradient in fiber organization that better imitates collagen fibers at tendon-to-bone insertion sites. The researchers hope to test their hybrid in rats within two years and begin clinical trials in five to 10 years.
Nanocomposite scaffolds are becoming popular tools in knee repair as well. Clinicians have successfully treated osteochondral knee defects with a biological scaffold of type I collagen and nanostructured hydroxyapatite (HA). The tri-layered biological implant consisted of a cartilage layer (100 percent type I collagen), a transition region (40 percent Nano-HA and 60 percent type I collagen) and a bone region (70 percent Nano-HA and 30 percent type I collagen). This type of implant, researchers contend, may become an easier, less morbid, cell-free “off-the-shelf” solution to focal defects of articular cartilage than either two-stage autologous chondrocyte engineering procedures or single-stage autograft mosaicplasty.
Electrospun scaffolds have shown promise in annulus fibrosus engineering, but more work is needed to perfect the process. Investigators’ first attempts to match the stiffness of native lamellar tissue failed miserably, however they have had limited success by using opposing collagen orientations of ± 30 degrees.
Although still in its infancy, nanotechnology perhaps shows the most potential in bone repair. Nano-coated implants have proven to be more conducive to osteoblast function, encouraging bone ingrowth, and engineered nanomaterials likely will be stronger and lighter than the current crop of contenders.
“For example, carbon nanotubes have the same stiffness as diamonds, and they are a hundred times stronger than steel—but only a sixth of its weight,” Baldini noted.
One of the major problems with man-made implants is their nanometric surface smoothness, which tend to induce the growth of fibrous tissue rather than bone. A nanotextured surface, on the other hand, can encourage the function of osteoblasts and reduce that of fibroblasts, experts claim. Materials like nanophase HA, nano-engineered titanium and cobalt-chromium-molybdenum promote osteoblast adhesion more than their conventional counterparts.
While preventing fibrous growths certainly would improve implant function, it single-handedly would not reduce the risk of failure—a complication that affects up to 5 percent of all total hip and knee replacement recipients. Researchers from the Massachusetts Institute of Technology (MIT), however, are coming to the rescue with a high-tech adhesive that more securely bonds implants to bone by promoting cell growth between natural and artificial body parts.
In a study published last summer, the MIT team and its collaborators from several other institutions reported the implant adhesive—a multi-layered coating of ceramic and nanolayers of polymers infused with proteins—worked so well on lab rats that it soon will be tested in humans.
The nanolayers, or super-thin sheets of material, hold therapies such as growth factors that attract and encourage the formation of bone cells, causing them to firmly attach to titanium implants. The coated implants required significantly more force to pull free than uncoated ones; indeed, the researchers said the resulting bond is so strong that under stress, the bone would fracture first before the interface with the implant.
“If you have bonding that is so strong that you actually break the bone, and you don’t get failure at the implant site, that would be very significant,” Guillermo Ameer, a professor of biomedical engineering at Northwestern University who was not involved in the study, divulged to the Boston Globe. “It’s pretty exciting if this is scaled up to humans.”
The implant coating works like a tiny, elegant machine. The top coating consists of repeating layers, each impossibly thin, that contain the bone growth factor BMP-2. The layers gradually break apart over a period of weeks, releasing BMP-2 into the body. The factor then stimulates stem cells in bone marrow to transform themselves into new bone cells.
The bottom part of the coating is made of a ceramic that mimics bone, thereby attracting bone cells to its surface. This side of the coating is attached to the implant, and recently formed bone cells tend to affix to this ceramic and grow outward, adhering like “superglue” to attach the implant to the bone, said Nisarg Shah, lead author of the MIT project.
The conventional approach to adhering implants uses a polymer called bone cement to attach them to bone. This cement can fragment and loosen over time. Moreover, because the body recognizes the cement as a foreign material, it often surrounds it with scar tissue, preventing bone from firmly attaching to the implant.
In contrast, most of the materials in the nanocoating either exist in the body or mimic natural substances such as bone. And most are already FDA-approved.
The nanocoating is flexible enough to use on surfaces other than metal implants. By applying it to polymer scaffolds that mimic body parts, “this kind of technology can be adapted for replacing bone,” said Paula Hammond, a professor at MIT who specializes in materials design and molecule delivery at very small scales. “This is another area where there is a lot of potential. There’s a range of needs that are associated with dentistry, dental implants and cranial-facial reconstruction.”
—Stephen King
It began, as most great ideas do, with a simple query.
For days, or maybe weeks back in 2012 (the memory is now a blur), Jay F. Whitacre pondered the feasibility of supersized batteries. Is it possible, he wondered, to make such large-scale devices?
Whitacre wracked his brain for answers but continually came up empty. Thinking about it, in fact, only led to more questions: Are there size limitations to batteries? Could they be made as big as a car or garage? A house? How difficult would it be to make a mega-battery? What would it cost? Are they even practical?
Lots of unanswered questions. And no Eureka! moment.
The proverbial “aha!” lightbulb eventually flickered in the hallowed fourth-floor corridor of Carnegie Mellon University’s Wean Hall. The building’s north wing houses Whitacre’s office and those of several other Materials Science and Engineering faculty, including Christopher J. Bettinger, Ph.D., director of CMU’s Biomaterials-based Microsystems and Electronics laboratory.
Whitacre quickly found a confidante in Bettinger upon his arrival at CMU two years ago. Connected by fate (their offices sit only four rooms apart), the pair quickly forged a friendship based on common interests: Both men hold doctorate degrees in materials science; both teach materials science and engineering courses at CMU (Bettinger also is a biomedical engineering instructor); and both spawned companies from their scientific passions (Whitacre’s Aquion Energy develops sodium ion batteries and energy storage systems while Bettinger’s AnCure designs brain aneurysm treatment devices).
As CMU neighbors, Whitacre and Bettinger often discussed their work and respective research. It was one of those conversations that led to an epiphany about batteries, though it was radically different from anything Whitacre had previously considered.
“Because we work in close proximity, we’ve thought about this [battery] idea a lot,” explained Bettinger, recipient of the National Academy of Sciences Award for Initiatives in Research. “He [Whitacre] develops batteries for large-scale energy storage. Rather than use expensive materials to build batteries, his idea is to use a simple, inexpensive material. It turns out that using aqueous electrolytes, or salt water-based electrolytes, are pretty important in moving ions around. Our bodies are made up of mostly salt water, so we started asking ‘what if?’ What if we used aqueous electrolytes from the body as a component of this battery? That could be interesting.”
Not exactly an Archimedes-like breakthrough for Whitacre’s big battery brainstorm, but a Eureka! moment nonetheless. The lightbulb was on.
And shining brightly on the opposite end of the battery size spectrum. Human electrolytes may not be practicable for supersized batteries but they’re an ideal power source for miniscule electronic devices. Making these batteries suitable for implantation inside the body, however, has proved challenging.
Most energy storage systems that power automated medical devices use potentially toxic electrode materials and electrolytes that compromise their safety. To become eligible for implantation, these storage systems must be composed of benign materials and able to operate in hydrated environments.
Last spring, Bettinger and Whitacre created edible power sources for medical devices using materials found in a daily diet. Their initial design involved a flexible polymer electrode and a sodium ion electrochemical cell that was folded into an edible pill encapsulating the tiny device.
Since then, the pair has improved upon their original design by using cuttlefish ink melanins. The naturally occurring melanins (pigment) in the mollusk’s ink have a higher charge storage capacity compared to other synthetic melanin derivatives when used as anode materials. And pigment-based anodes are an essential component of sodium-ion batteries, the technology Whitacre has pioneered through his company.
“We discovered that melanin—the pigment in your eyes, your skin and your hair—has an interesting cross-section of properties that make it ideal for powering an ingestible electronic device. One of the more interesting aspects of melanin is the nanoscale structures that occur naturally,” Bettinger told Orthopedic Design & Technology. “This nanoscale structure found in nature is very similar to the structure you might find in a battery that powers your cell phone or laptop. There’s a consequential structural conformity between melanins and high-performance batteries. We took that idea and ran with it, using melanin to make batteries that could power edible electronic devices in the future.”
Ingestible electronics, nanobiomaterials, microscopic sensors and tiny biomimetic scaffolds are just a few of the probable treatment options in that future as nanotechnology further ingrains itself in the medical device and pharmaceutical industries. Industry experts predict the global nanomedicine market to achieve a compound annual growth rate of 12.3 percent through 2019, reaching a net worth of $177.6 billion, according to Transparency Market research statistics.
‘Transformational’ Technology
Nanotechnology, in its most basic form, is the study, production and manipulation of matter at the atomic/molecular level (less than 100 nanometers). The concept was first proposed 55 years ago by theoretical physicist Richard P. Feynman during a lecture to the American Physical Society. In his speech—now considered a seminal event in nanotech’s relatively short history—Feynman laid the conceptual foundation for small-scale physics, envisioning a world of dense computer circuitry, extremely powerful electron microscopes, and swallowable surgeons. He conceived such prognostic notions by asking the same simple question that has spawned countless other Eureka! moments throughout the ages: What if?
“It is a staggeringly small world that is below,” Feynman said in his 1959 lecture, aptly titled, “There is Plenty of Room at the Bottom.” “I am not afraid to consider the final question as to whether, ultimately—in the great future—we can arrange the atoms the way we want; the very atoms, all the way down! What would happen if we could arrange the atoms one by one the way we want them (within reason, of course...)?”
Here’s what happens: Those atoms abide by the laws of quantum mechanics, affecting the optical, electrical and magnetic behaviors of a material. Also, surface area to volume ratio skyrockets, drastically altering the properties of a nanostructure and triggering some very unconventional conduct. Opaque substances such as copper, for example, become transparent, while inert elements become catalysts (platinum); stable materials turn combustible (aluminum), golds and other solids morph into liquids (at room temperature), and insulators become conductors (silicon).
In the nanotech world, all bets indeed are off.
Yet it is those anomalies—particularly the significantly higher surface area associated with nanomaterials—that hold so much promise for the orthopedic device industry. Research has shown higher surface area can bolster the interaction between implants and host bone, improving osseointegration by promoting both differentiation of mesenchymal stromal cells and the adsorption of extracellular adhesion molecules necessary for osteoblast function.
“Nanoscience is making its way into many key areas of orthopedics, including in clinical practice,” Nicola Baldini, an orthopedic surgeon and associate professor of orthopedics at the University of Bologna, Italy, said at the 15th EFORT Congress in London, United Kingdom, in June. Baldini also is a visiting professor at Kyoto Prefectural University of Medicine in Kyoto, Japan, and head of the Laboratory for Orthopedic Pathophysiology and Regenerative Medicine.
“Research into therapies that involve the manipulation of individual genes or the molecular pathways that influence their expression is on the rise,” he noted. “Nanotechnology holds enormous potential for orthopedics.”
The magnitude of that potential clearly is evident, too, in the various applications now underway: Silver nanoparticles, for instance, are being used to prevent infections, while nanocomposite scaffolds show promise in repairing osteochondral knee defects and nanofibers are proving an effective alternative to thick, stiff surgical mesh.
Smith & Nephew plc is a virtual pioneer in the nanotech world, having released a nanocrystalline antimicrobial burn dressing back in 1998. The nanocrystals in the firm’s Acticoat product line release silver ions in the dressing and sustain release for up to seven days, killing such virulent germs as MRSA (methicillin-resistant Staphylococcus aureus) and VRE (vancomycin resistant enteroccocus).
AcryMed Inc.’s SilvaGard also is a microbial murderer, but it masquerades as an implant coating.
SilvaGard-treated devices are immersed in a liquid solution of silver nanoparticles, coating all exposed surfaces with the antimicrobial agent. The Beaverton, Ore.-based company contends its technology can resist germs for “days, weeks or months” depending upon the device application. The period of efficacy can be varied by changing the amount of silver applied to the product during treatment, thus allowing device manufacturers to customize the process to best meet specific requirements. The U.S. Food and Drug Administration (FDA) approved AcryMed’s SilvaGard technology in 2005, allowing I-Flow Corporation to market its ON-Q Silver Soaker regional anesthesia delivery catheters.
Matthew MacEwan is hoping to gain the FDA’s blessing for a synthetic polymer surgical mesh made from individual strands of nanofibers. Initially developed by his startup firm NanoMed LLC to treat brain and spinal cord injuries, the mesh also could be used to mend hernias, fistulas and other wounds.
Existing surgical mesh used to repair the protective membrane covering the brain and spinal cord typically is derived from pig or cow skin, making it thick, stiff and difficult to work with. The material MacEwan developed with Jingwei Xie, Ph.D., and two other Washington University (St. Louis, Mo.) scholars is thin, flexible and more likely to integrate with the body’s own tissues.
“It’s almost like a cloth,” said MacEwan, who also is perfecting a surgical mesh for neurosurgical procedures. “But it’s designed on a nanoscopic scale. To put that into perspective, every thread of the mesh is thousands of times smaller than the diameter of a single cell.”
Resembling gauze, the sticky DuraStar Dural Substitute is composed of multiple layers of nanofibers and can be custom-sized for different uses. When implanted, cells grow alongside the mesh’s individual nanofibers; the mesh gradually degrades in nine to 12 months, leaving the body’s own tissue in place.
“We’ve taken the whole idea of surgical mesh and pushed it into a new direction,” MacEwan told a Washington University reporter. “It’s not just a foreign material you’re putting into the body. The nanofabricated nature of the mesh creates a scaffold that cells can easily penetrate and populate to recapitulate the body’s tissues.”
Nanofiber scaffolds also play a key role in speculative new rotator cuff repair treatment. Using a $293,000 National Institutes of Health grant, researchers from Marshall University in West Virginia are working on a way to replicate Mother Nature’s tendon-shoulder bone attachment. Their initial design combines a nanofiber scaffold with adipose-derived stem cells to promote tissue repair after rotator cuff surgery, one of the most common orthopedic procedures in the United States (roughly 300,000 are performed annually, according to industry statistics).
Current rotator cuff repair methods have a failure rate that ranges between 20 percent and 90 percent, due largely to the manner in which tendons are reattached to the bone. Marshall University researchers have found that controlling the mineralization of electrospun nanofibers greatly enhances their mechanical properties (i.e., stiffness, ultimate tensile strength and toughness), creating scaffolds with gradient in fiber organization that better imitates collagen fibers at tendon-to-bone insertion sites. The researchers hope to test their hybrid in rats within two years and begin clinical trials in five to 10 years.
Nanocomposite scaffolds are becoming popular tools in knee repair as well. Clinicians have successfully treated osteochondral knee defects with a biological scaffold of type I collagen and nanostructured hydroxyapatite (HA). The tri-layered biological implant consisted of a cartilage layer (100 percent type I collagen), a transition region (40 percent Nano-HA and 60 percent type I collagen) and a bone region (70 percent Nano-HA and 30 percent type I collagen). This type of implant, researchers contend, may become an easier, less morbid, cell-free “off-the-shelf” solution to focal defects of articular cartilage than either two-stage autologous chondrocyte engineering procedures or single-stage autograft mosaicplasty.
Electrospun scaffolds have shown promise in annulus fibrosus engineering, but more work is needed to perfect the process. Investigators’ first attempts to match the stiffness of native lamellar tissue failed miserably, however they have had limited success by using opposing collagen orientations of ± 30 degrees.
Although still in its infancy, nanotechnology perhaps shows the most potential in bone repair. Nano-coated implants have proven to be more conducive to osteoblast function, encouraging bone ingrowth, and engineered nanomaterials likely will be stronger and lighter than the current crop of contenders.
“For example, carbon nanotubes have the same stiffness as diamonds, and they are a hundred times stronger than steel—but only a sixth of its weight,” Baldini noted.
One of the major problems with man-made implants is their nanometric surface smoothness, which tend to induce the growth of fibrous tissue rather than bone. A nanotextured surface, on the other hand, can encourage the function of osteoblasts and reduce that of fibroblasts, experts claim. Materials like nanophase HA, nano-engineered titanium and cobalt-chromium-molybdenum promote osteoblast adhesion more than their conventional counterparts.
While preventing fibrous growths certainly would improve implant function, it single-handedly would not reduce the risk of failure—a complication that affects up to 5 percent of all total hip and knee replacement recipients. Researchers from the Massachusetts Institute of Technology (MIT), however, are coming to the rescue with a high-tech adhesive that more securely bonds implants to bone by promoting cell growth between natural and artificial body parts.
In a study published last summer, the MIT team and its collaborators from several other institutions reported the implant adhesive—a multi-layered coating of ceramic and nanolayers of polymers infused with proteins—worked so well on lab rats that it soon will be tested in humans.
The nanolayers, or super-thin sheets of material, hold therapies such as growth factors that attract and encourage the formation of bone cells, causing them to firmly attach to titanium implants. The coated implants required significantly more force to pull free than uncoated ones; indeed, the researchers said the resulting bond is so strong that under stress, the bone would fracture first before the interface with the implant.
“If you have bonding that is so strong that you actually break the bone, and you don’t get failure at the implant site, that would be very significant,” Guillermo Ameer, a professor of biomedical engineering at Northwestern University who was not involved in the study, divulged to the Boston Globe. “It’s pretty exciting if this is scaled up to humans.”
The implant coating works like a tiny, elegant machine. The top coating consists of repeating layers, each impossibly thin, that contain the bone growth factor BMP-2. The layers gradually break apart over a period of weeks, releasing BMP-2 into the body. The factor then stimulates stem cells in bone marrow to transform themselves into new bone cells.
The bottom part of the coating is made of a ceramic that mimics bone, thereby attracting bone cells to its surface. This side of the coating is attached to the implant, and recently formed bone cells tend to affix to this ceramic and grow outward, adhering like “superglue” to attach the implant to the bone, said Nisarg Shah, lead author of the MIT project.
The conventional approach to adhering implants uses a polymer called bone cement to attach them to bone. This cement can fragment and loosen over time. Moreover, because the body recognizes the cement as a foreign material, it often surrounds it with scar tissue, preventing bone from firmly attaching to the implant.
In contrast, most of the materials in the nanocoating either exist in the body or mimic natural substances such as bone. And most are already FDA-approved.
The nanocoating is flexible enough to use on surfaces other than metal implants. By applying it to polymer scaffolds that mimic body parts, “this kind of technology can be adapted for replacing bone,” said Paula Hammond, a professor at MIT who specializes in materials design and molecule delivery at very small scales. “This is another area where there is a lot of potential. There’s a range of needs that are associated with dentistry, dental implants and cranial-facial reconstruction.”