Sneaky Nanotech: Nanotubes and Nanowires ‘fool’ your body into growing bone where doctors want it

Let’s say you’re skiing. You’re on one of Colorado’s famous mountain peaks, and you’re flying down the mountain at 40 miles-per-hour. But – let’s be honest here – you’re skill isn’t quite what you would like it to be; you catch an edge and down you go. But as you fall down, you give-in to your natural reflexes: You try to catch yourself and, in the process, you snap your wrist.

Wrist fractures are perhaps the most common break that people under the age of 75 suffer. And, most of the time, healing them isn’t too complicated: You have a doctor set it in place, confine it to a cast and you wait a few weeks for nature to take its course.

Titanium nanotubes grown in Dr. Popat's lab, which can be used to fill-in gaps in severely damaged skeletal structures and act as scaffolding for bone cells to repopulate the wounded area. These same tubes could also be filled with antibodies and used for drug delivery to specific sites in the body.

But what if it’s worse than that? What if when you catch that edge and are sucked to the ground, your arm doesn’t just land cleanly on the turf? What if it gets caught in a tree branch and your body’s ruthless momentum wraps your once-straight radius and ulna bones around the tree’s trunk – breaking them multiple times? Ouch, right?

Well, more severe or complicated injuries, such as this, are a heap more difficult for doctors to mend. In the not-too-distant past a complex fracture or a crushing blow to a joint meant a permanent disability. With a compound fracture, the trouble for doctors is often that some bone is missing; so either a process must be used to coax the patient’s bone to grow in the empty hole left by the injury, or new bone – or an artificial substitute – must be grafted in place.

But there are few substitutes that function as well as bones – after all, our skeletal system has been continually shaped and refined through some 500 million years of evolution. Consequently, grafting usually amounts to a bone transplant, where bone is taken either from another part of the body or, occasionally, from other animals. But when these options are not available, foreign materials are sometimes used, such as hydroxylapatite, which is a naturally occurring mineral – actually, it’s a type of rock – which happens to be the primary component of bones – about 70 percent of bones are hydroxylapatite by mass.

Yet for really severe skeletal damage – for which using bone is not realistic – artificial substitutes have been the norm. Of course, the most common serious injury for which this is often the case is a fractured hip – which happens to be the most common break suffered by people over the age of 75. Frequently, when a hip is broken the entire hip joint is ruined. This means that if the patient wants to avoid being permanently crippled, orthopaedic bone and joint substitutes must be placed inside the body. In addition to being a costly and sometimes risky procedure, hip replacements suffer from a very fundamental flaw: They’re still not real bone.

Hip replacement techniques have been around since 1925, when Doctor M. N. Smith-Petersen designed the first artificial hip, which was then made of glass. Naturally, glass couldn’t hold-up to the day-to-day stresses that human beings put on their hips, so a gradual search for a new or better material began. Over time, cobalt-chromium alloys were developed as the support structures, which were very strong, and polyethylene cushions were used to give the joint lubrication and some comfort. Today, it is estimated that by 2010 some 1.3 million people will have an artificial joint in the United States alone, and those will be primarily fabricated from these – or similar – materials.

But although metal alloys are exceptionally strong, they still can’t measure up to our natural skeletal system. Why? Simply because bones grow. Even though we stop growing in early adulthood, our bones are constantly building-on, regenerating themselves, and mending potentially millions of microscopic fractures. So as the wear-and-tear of walking and athletics breaks this support system down, it is constantly battling to build itself back up. Metal cannot do this. Every step taken with a metal hip makes that hip weaker. And it does not get better.

Florescent image of stem cells -- the bone variety -- growing on the stock of titanium nanotubes in Popat's lab. Data like this have shown that bone cells essentially recognize these nanotubes as other bone cells.

It is estimated that over 500,000 total joint replacements, primarily hips and knees, are used every year in the United States, according to Dr. Ketul Popat, a professor in the School of Biomedical Engineering at Colorado State University. Popat is the director of the Biomaterials and Surface Micro/Nano-Engineering Laboratory at CSU, which is designing new methods for bone grafting, joint replacements and other orthopaedic applications, all by using nanotechnologies to convince real bone cells to grow where they otherwise would not.

“It is the surface that is the most important part,” Popat says. “You need to fool these bone cells into thinking they’re interacting with other bone cells.”

According to Popat, bone cells are guided in what they do and the functions they carry out by the structures and materials that are immediately around them. Therefore, the surface chemistry of what a bone cell happens to bump into is what tells the cell where it is in the body and, accordingly, if it should produce more cells, or not.

In Dr. Popat’s lab a biocompatible, biodegradable polymer is engineered – it is made of a material called caprolactone. The polymer is manufactured, essentially, in the form of thousands of tiny nanowires – ranging in diameter from 10 to 500 nanometers and capable of being grown up to 20 microns in length – attached to a surface substrate. These nanowires can be used quite literally as scaffolding for bone cells to climb and build upon.

Popat’s research has shown that bone cells can be tricked into thinking these nanowires are like the bone’s natural support system, and can grow, differentiate and spread – potentially – into previously damaged areas of the body. Furthermore, the polymer degrades with time, so to allow the bone itself to eventually take-over, like a plaster hardening in a mold.

For bone-healing techniques that may require a more robust scaffolding structure – such as hip replacements – Popat has proposed using nanostructured metal-oxide thin film nanotubes, of controllable architectures, which can range from the nano to micro-dimensional scales. These nanotubes can be grown like a field of grass and filled into skeletal gaps. They have already been shown to trick bone cells into allowing them to support stem cell clusters.

As if that were not enough, Popat is also investigating the possibility that these nanowires and nanotubes can be used to deliver antibiotics or other medicines to such locations as compound fractures or joint replacements. Currently, such drugs are often administered orally or intravenously; meaning that the drug itself is forced to circulate through the entire bloodstream – or sometimes the digestive system too – before reaching its target. Popat says that these medicines can be placed in nanotubes designed to release their healing ingredients at particular times, or rates.

“We can imagine these nanotubes as test tubes filled with antibodies,” he says. “By targeting the site we can reduce the amount of drug that is needed. So we are reducing the amount of drug taken by about 500 percent.”

Nanowires made from a polymer that can also act as scaffolding for bone cells to grow and make repairs upon. The polymer degrades with time, allowing the bone cells to eventually take back their load-bearing duties.

Popat is also looking into the possibility that nanowires similar to his polymer scaffold can be used to guide neurons that have been damaged. This could lead to advances in the treatment of spinal cord damage and the roots of paralyzation.

So, maybe one day soon, no matter how nasty your tumble down the mountain happens to be, doctors, with the help of nano-engineers, will have no problem fixing you up.

Related Sites

• stats on bone fractures: from about.com
• fracture: definition of a fracture and compound fractures
• bone graft: online encyclopedia article
• bone evolution: journal article discussing the roots of skeletal evolution
• hydroxylapatite: mineral data
• composition of bones: article discussing the makeup of several hard tissues in the body
• Doctor M. N. Smith-Peterson: a brief history of joint replacement
• cobalt-chromium alloys: physical properties of cobalt and its alloys
• artificial joint statistics: supplied by Dr. Popat
• caprolactone: encyclopedia article
• nanowire: HowStuffWorks article
• nanometer: encyclopedia article
• micrometer: encyclopedia article
• substrate: encyclopedia article
• bone cells: University of Washington definition
• nanotubes: NCF article
• antibiotics: industry definition
• neuron : American Medical Association illustrated Web site

Further Information for Students or Professionals

• Dr. Ketul Popat: professional profile at CSU
• School of Biomedical Engineering: department homepage
• Colorado State University: university homepage
• Biomaterials and Surface Micro/Nano-Engineering Laboratory : laboratory Web site with results and data

Selected Publications

1. Joshua R. Porter, Andrew Henson, Stewart Ryan and Ketul C. Popat, "Biocompatibility and Mesenchymal Stem Cell Response to Poly(?-caprolactone) Nanowire Surfaces For Orthopedic Tissue Engineering", Tissue Engineering A (2009)
2. Joshua R. Porter, Andrew Henson and Ketul C. Popat, "Biodegradable Poly(e-Caprolactone) Nanowires for Bone Tissue Engineering Applications", Biomaterials 30(5) (2009) 780-788
3. Timothy Ruckh, Joshua R. Porter, Nageh K. Allam, Xinjian Feng, Craig A. Grimes, Ketul C. Popat, "Nanostructured tantala as a template for enhanced osseointegration", Nanotechnology 20(4) (2009) 045102 (7pp)
4. Kristy M. Ainslie, Sarah L. Tao, Ketul C. Popat, and Tejal A. Desai, "In vitro inflammatory response of nanostructured titania, silicon oxide, and polycaprolactone", Journal of Biomedical Materials Research, In press (2009)
5. Ketul C. Popat, Sarah L. Tao, James Norman and Tejal A. Desai, "Surface Modification of SU-8 for Enhanced Biofunctionality and Nonfouling Properties", Langmuir 24(6) (2008) 2631-2636
6. Ketul C. Popat, Matthew Eltgroth, Craig A. Grimes and Tejal A. Desai, "Decreased S. Epidermis adhesion and increased Osteoblast functionality on antibiotic-loaded nanotubes", Biomaterials 28(32) (2007) 4880-4888

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