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The Orthopedic “Silver” Lining
How antimicrobial surface nanotechnology is making devices safer than ever
Bruce L. Gibbins, PhD
AcryMed, Inc.
 Bruce L. Gibbins, PhD AcryMed, Inc. |
Driven by the concerns of surgeons, patients and insurance companies, medical device manufacturers are now compelled to step in to help solve this mounting national medical problem.
It is fortunate that, in recent years, medical science has rediscovered the dramatic efficacy of time-honored silver as an antimicrobial technology to help fight and eliminate hospital-based infections. The absence of widespread microbial resistance to silver, coupled with the science of nanotechnology, is the key feature that has provoked the resurgence of interest in the silver’s medicinal properties.
Device manufacturers and surgeons are increasingly becoming more impressed with the antimicrobial effectiveness of silver and are now asking, “Why not make the device itself antimicrobial?” Most recently, dramatic results have indicated that this is possible through silver antimicrobial nanotechnology. With recent FDA approval, this technology maximizes the antimicrobial effectiveness of silver by utilizing the fundamentals of nanotechnology to render medical devices antimicrobial.
How Orthopedic Devices Spread Infection
How does virulent, device-related infection occur in patients? Micro-organisms normally grow as a free living cell, a condition that is often referred to as the planktonic form. This version has been studied by researchers and consequently led to the development of antibiotics, which have been the mainstay of infection prevention since the discovery of penicillin in the early 1900’s.
Over time, the scientific community has learned that almost all medically relevant microbes can establish a fast-mutating, adherent lifestyle wherein the organism attaches to a surface in the body where it forms colonies that spread. A cohesive film-like layer forms over the colony to protect it—hence the term “biofilm.” Once attached to an orthopedic device’s surface, this biofilm can be a major cause of infection spreading in the body.
In recent years, researchers have studied biofilms and realized that they are abundant in nature. In fact, most species of microorganisms exist in biofilm in their normal habitats, and only use the free-floating planktonic state to spread to new areas to populate.
Not all biofilms are harmful. In terrestrial environments, biofilms help to purify water in streams. They are easily recognized by the slime that covers the rocks in streams and rivers.
Pathogens, however, in their biofilm state, are very difficult to eliminate. They are far less controllable than their free-living cousins because they mutate quickly, are extremely resistant to the body’s defense mechanisms and are often found 1,000-fold in density living deeply in the biofilm, making them more resistant to antibiotics than their free living counterparts. The polysaccharide film that forms over the colony protects it further.
Why Devices Promote Infection
 AcryMed senior scientist Balu Karandikar, PhD studies an orthopedic substrate material treated with silver antimicrobial nanoparticle surface deposition technology. Photo Courtesy of AcryMed, Inc. |
However, once antibiotic therapy is complete, the biofilm might signal the release of a new wave of organisms. This process leads to recurrent infection, which is typical of device-related infections.
Here’s an example: A 58-year-old man has double knee replacement surgery and an uneventful recovery. About seven weeks later, he develops an infection that responds well to antibiotics. However, soon after the antibiotic course is complete, a new infection develops. The cycle repeats several times and eventually necessitates the removal and replacement of both knee prosthetics.
Implanted and percutaneous devices provide surfaces that readily support biofilm formation, as they are inert and biocompatible and interface with a highly nutritive environment. Orga-nisms that may enter the surgical field from the blood or during surgery may attach and begin proliferation. The trauma of surgery often decreases the perfusion of the area temporarily, which can, in turn, decrease natural immunologic defenses.
Even prophylactic antibiotics might not readily reach the device when these organisms are most vulnerable. The danger comes when this surgical site heals, because a ticking time bomb can explode into unmanaged infection when the biofilm grows to such density that it can keep releasing organisms to test for new environments.
A Silver Coating Fights Infection
Today, the medical device and healthcare industries are waging war against device-related infection by facing head-on the key challenge to preventing biofilm: fighting bacteria from colonizing on surfaces of medical instruments. With this goal in mind, an increasing number of orthopedic manufacturers and surgeons are investigating the very real possibility of making the device itself antimicrobial.
Viable candidates being evaluated to achieve this goal include antibiotic coatings, antiseptic impregnations such as chlorohexidines and, most recently, the use of silver. Advances in nanotechnology, using silver, are increasingly being examined for fighting infection because bacteria-resistant silver provides a robust antimicrobial surface to efficiently inhibit biofilm adherence.
The medicinal properties of silver have been known for thousands of years. The Egyptians, Greeks and Romans protected the quality of their water by drinking it from silver goblets. Even our own pioneers placed silver coins in their canteens to help make stream and lake water safe for consumption.
Although silver is not the only heavy metal with antimicrobial properties—mercury and lead also have been used in the last 200 years to treat infections—silver is the only one without toxic side effects. In the late 1800’s, ionic silver proved very effective in low doses and was a dominant antimicrobial until the discovery of penicillin in the early 1900’s. Although antibiotic drugs such as penicillin became preferred therapies for controlling microbes, silver still remains popular for other uses, such as serving as an antimicrobial for burns and as the favored antimicrobial in topical wound dressings.
The re-emergence of using silver in the battle against device-related infection has occurred for many reasons. First, silver has been used in modern medical applications for more than 120 years without any widespread microbial resistance to its action. Second, silver is “broad spectrum”—meaning, it kills most bacteria, fungi and yeast forms of organisms. Third, silver is safe for medical use because it is rapidly cleared from tissues and does not kill bodily cells in concentrations necessary to kill microbes. Finally, silver is inexpensive and safe to handle.
Orthopedic device manufacturers, knowing the lead time and expense of developing antimicrobial surfaces for devices, recognize that using an agent such as silver will give their device longevity in the market.
While highly specialized pharmaceutical antibiotics act on targeted microorganisms, studies show that these organisms mutate to escape the antibiotic modes of action. The use of ionic silver, however, overcomes this limitation because its mechanism of action simultaneously attacks multiple sites (up to 10) within cells. Although this multifunctional action results in non-specific killing of all organisms within its range, its action does not lead to resistance because microbes are unable to simultaneously develop mutations in each susceptible site and consequently overcome silver’s antimicrobial effect.
To date, no evidence has shown any silver-resistant bacteria among the medically relevant strains.
How Silver Has Been Used
Current commercial silver antimicrobial technologies used for medical devices fall into two categories: direct incorporation and surface application.
Direct incorporation involves the addition of a form of silver or silver salts into the material that is used to make a device. This approach is most applicable to non-metallic devices.
This method poses several limitations. Incorporation into the polymer changes the material’s composition, which often requires the manufacturer to spend extra time re-qualifying or clearing the product for market. In addition, the silver reservoir is only effective at the device surface, where it comes in contact with bodily fluids.
Applying silver onto a device’s outside surfaces has been accomplished through a variety of methods, including electroplating, ion plasma deposition, sputter coating and even by “painting.” The main advantages of surface application are that the material’s composition remains unchanged—thereby necessitating regulatory approval of only the surface application—and that the antimicrobial agent is concentrated where it will do the most good.
However, the main disadvantage of surface deposition is the resultant alteration in surface properties. Many coating technologies actually apply a layer of metal that is intolerant of flexing and stretching, which causes cracking and peeling.
Silver Nanoparticles: A Revolution
Newer silver antimicrobial technology, approved by the FDA, now maximizes the antimicrobial effectiveness of silver by utilizing the fundamentals of nanotechnology.
Silver’s antimicrobial activity is dependent on the release of ionic silver made possible when metallic silver comes in contact with air or moisture—in this case, bodily fluids—and forms silver oxide through the process of oxidation. This is where nanotechnology comes into play.
Nanotechnology is the science of particles the size of one billionth of a meter—so tiny, they cannot be seen by the human eye. Silver particles with a diameter in the nano realm have a great surface area relative to their mass. Increased surface area means increased exposure to air and moisture and, therefore, greater antimicrobial activity. Nano-size silver particles on the surface of a medical device can achieve antimicrobial efficacy on a level never before clinically validated or realized.
The new silver nanoparticles in antimicrobial technology rely on the formation of ~10 nm diameter nanoparticles of silver that stick tightly to orthopedic device surfaces. These nanoparticles carry about 25,000 atoms of silver in each particle. Most of the atoms are in the metallic form, but plenty of surface area is available for oxidation due to the vast surface areas of small particles. Silver nanoparticles bind tenaciously to most device surfaces, ranging from polymers to metals. The reaction can be carried out in aqueous solution or solvents. Once the application has reached the desired density, the device is rinsed, dried and then ready for use following any assembly or terminal treatment. The technology is compatible with all methods of terminal sterilization.
This technology offers several advantages over other surface applications. First, the application occurs wherever the reaction solution is allowed to flow. For example, this means that both the internal and external surfaces of catheters receive the treatment. Second, a device’s dimensions would have no measurable changes because the application is only nanometers in thickness. Third, even elastic devices can be treated. For example, silver nanoparticle coatings on flexible polymers used for balloon catheters will not peel or crack when the balloon is inflated.
Another advantage of silver nanotechnology is that the density of the surface treatment can be dialed to the needs of the device. To date, more than 30 different polymers and metals have been treated successfully with this new silver antimicrobial technology, including Teflon.
Device-related infections threaten the lives of millions of Americans each year. Furthermore, hospital environments are compromised and left vulnerable to insidious bacterial growth.
Both orthopedic manufacturers and researchers are investigating the revolutionary use of nanotechnology in silver applications for infection warfare. This powerful, highly adaptable, nontoxic technology holds immense promise in challenging and eliminating the virulent and life-threatening strains found in hospital infections.
