AAOS Now

Published 5/1/2007
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Samir Mehta, MD; Ryan M. Nunley, MD; Alex Jahangir, MD; Alok D. Sharan; the Washington Health Policy Fellows

Nanotechnology: From nano to micro to macro

Nanotechnology is the precision placement, measurement, manipulation, and modeling of matter that consists of 4 to 400 atoms.

To put that in perspective, one nanometer—one billionth of a meter—is 1/75,000 the width of a human hair. This would be the equivalent of comparing a marble with the planet Earth.

The range below 100 nanometers is important because at this small size, the classic laws of physics change. The result is novel properties that enable researchers to produce new materials with the exact characteristics they desire: smaller, stronger, and tougher than current materials. The worldwide market for nanotechnology is expected to reach $1 trillion by 2015.

In the beginning…
The modern history of nanotechnology began in 1959 when Richard Feynman, a Nobel Prize-winning physicist, delivered a speech titled “There’s Plenty of Room at the Bottom.” Feynman told his audience that he was unaware of any scientific laws suggesting that it would be impossible to manipulate matter atom by atom. His speech is credited with inspiring scientists to probe into the nanoscale in hopes of precisely moving and controlling individual atoms.

Feynman even offered two $1,000 prizes: one prize for creating a tiny cubic motor 0.4 mm in each direction; another for shrinking the page of a book to 1/25,000 of its standard size, which would result in a page about 100 nanometers high. The first prize was claimed less than one year later, but it took 26 years for the second prize to be claimed.

The human body demonstrates true nanotechnology in action. The biologic systems at work in cells and in nature contain nanoscale systems. Specifically, bone is composed of numerous nanostructures, such as collagen and hydroxyapatite, which provide a unique nanostructure for protein and bone cell interactions in the body. Whether it’s discovering how DNA stores and transfers information about our genetic makeup or increasing our understanding of the calcium hydroxyapatite nanostructure of bone, nanotechnology holds massive potential for orthopaedics.

Orthopaedics and nanotechnology
The AAOS recently participated in an open meeting with the U.S. Food and Drug Administration on nanotechnology, and submitted comments outlining the orthopaedic community’s position. The statement discussed both the future potential of nanotechnology within the field of orthopaedics and the need for further research; it also commented on environmental drug and device regulatory issues.

Developing nanotechnology requires an integrated understanding of and collaboration between multiple scientific fields, including biology, physics, chemistry, materials science, computer science, mechanical engineering, and electrical engineering.

Nanomaterials have been proposed as the next generation of improved orthopaedic implant materials, with the aim of improving surface properties to create an environment more conducive for osteoblast function and bone ingrowth. Nanotubes, building blocks for macro nanostructures, are about one-sixth the weight and nearly 100 times stronger than steel. For example, nanostructured ceramics can reduce friction and wear problems associated with joint replacement components.

Biologically active molecules, added to the implant surface via nanotechnology, represent breakthroughs in guided interfacial osteogenesis. This methodology offers an enormous potential in genetic counseling and promoting osteogenesis.1 Osteoblasts cultured on nanostructured titanium display as much as three times more calcium than those cultured on microstructured (conventional) titanium.2

Current applications of nanotechnology include the development of biodegradable, tissue-engineered ligament replacements, fluorescent biologic probes used in imaging of bone tumors, site-specific targeted drug delivery, cancer therapies to heat and burn tumors, and gene therapy. Hydrogels have been constructed to replace articular cartilage with mechanical properties far superior to current surfaces.3 The biologic responses to nanoparticles of metal, polymeric and ceramic corrosion, and wear debris are being investigated to determine if they contribute to implant failure and/or long-term systemic effects.

The most notable future application of nanotechnology with the greatest near-term impact in orthopaedics may be in drug delivery.4 Nanotechnology enables drug delivery mechanisms that can send biologically active materials directly to the location where they are beneficial. Nanofabricated surfaces may make it possible to target bone tumors and enable specific delivery of therapeutic enzymes to tumor cells. Nanocapsules of anti-inflammatory medications provide prolonged action in treating arthritis. Nanofibrous membrane wound dressings are encouraging advances that aim to reduce postoperative infection rates and promote faster healing.

An example of this type of wound dressing is already in clinical application. Silver (long known to have significant medicinal benefits) is broken down and then built back up into silver nanocrystals atom by atom. At the nanoscale level, silver’s therapeutic effects become several times more potent. The increased surface area means faster chemical reactions, greater solubility, and sustained release of silver ions, which kill more than 150 pathogens. This nanocrystalline silver has been packaged to create a dressing for wounds and burns.

Although preliminary attempts to incorporate nanophase materials into orthopaedic implants seem promising, several urgent questions remain unanswered. First and foremost, the safety of nanoparticles, once in the human body, has yet to be proven—from a manufacturing point of view and when used in full or as components of an implantable device.

Because such particles are smaller than many pores of biologic tissues, rigorous safety studies must be conducted before further consideration of implantable nanomaterials is undertaken.5 Nanoparticles may easily become dislodged from implants during surgery or from fragmentation of articulating components of a joint prosthetic composed of nanophase materials. Although preliminary in vitro studies seem to indicate that particulate wear debris at the nanometer level has less adverse influence on bone cell viability than micron-sized debris, more in vivo testing is needed to evaluate their efficacy.

Nanotechnology poses interesting challenges for the orthopaedic community and regulators. The potential for novel treatments is apparent but risks must be mitigated. Understanding the long-term biologic consequences of nanotechnology products will be critical. In vitro and in vivo tests will need to be developed to predict human reaction to nanotechnology products. Orthopaedic surgery has traditionally dealt within the “macro,” but the introduction of nanotechnology may begin a paradigm shift within the field.

The Washington Health Policy Fellows include Samir Mehta, MD; Ryan M. Nunley, MD; Alex Jahangir, MD; Alok D. Sharan, MD; John Flint, MD; Jamie Genuario, MD; Sharat K. Kusuma, MD; and Anil Ranawat, MD. Please send your comments to aaoscomm@aaos.org

References

  1. Letic-Gavrilovic A, Scandurra R, Abe K. Genetic potential of interfacial guided osteogenesis in implant devices. Dent Mater J. Jun 2000;19(2):99-132.
  2. Palin E, Liu H, Webster T. Mimicking the nanofeatures of bone increases bone-forming cell adhesion and proliferation. Nanotechnology. 2005(16):1828-1835.
  3. Murosaki T, Gong JP, Osada Y. [Creation of artificial cartilage by nanotechnology]. Nippon Rinsho. Feb 2006;64(2):206-214.
  4. Tasker LH, Sparey-Taylor GJ, Nokes LD. Applications of Nanotechnology in Orthopaedics. Clin Orthop Relat Res. Jan 11 2007.
  5. Park G, Webster T. A Review of Nanotechnology for the Development of Better Orthopedic Implants. J of Biomed Nanotechnology. 2005;1:18-29.