Originally Published MDDI May 2005
Nanoengineering could solve problems associated with applying silver as an antimicrobial agent to medical devices.
David Tobler and Lenna Warner
|The top photo depicts the polypropylene without nanotech silver applied, while the bottom photo has had ordered nanostructures of silver oxide
applied by IPD processing.
The number of infections linked to medical devices has fueled an explosion of research in surface science. The goal is to find a way to prevent the conditions that trigger life-threatening bloodstream infections.
Nosocomial, or hospital-related bacterial infections, are estimated to be the fifth-leading cause of death in the United States, after heart disease, cancer, stroke, and pneumonia or flu.1 The Centers for Disease Control estimate that nosocomial infections cost hospitals more than $2300 per patient for diagnosis and treatment. Many instances, such as vascular catheter infection, can cost $25,000 per episode. Overall, the infections cost hospitals $4.8 billion annually in extended care and treatment.
Pathogens mutate quickly and render antibiotics useless in fighting them. A great majority of healthcare-acquired infections involve many of the pathogens displaying antimicrobial resistance.2 Therefore, silver's medicinal importance in combating these infections cannot be underestimated.
Silver is effective across a broad range of bacteria and against mutating pathogens. It is also effective in blocking fungi and yeasts known to cause disease.
Silver is harmless to the body at bacterial effective levels. Humans take in about 70–88 µm of silver each day. Other heavy metals, such as mercury and lead, can bond chemically and accumulate in the body, which can inhibit metabolism. By contrast, research suggests that 99% of silver is readily excreted.3 Silver is, for the most part, nontoxic. Cases of extreme exposure have caused upper respiratory or mild eye irritation, and prolonged exposure can cause argyria. However, silver oxide is an effective antimicrobial at levels as little as 1 ppm, so toxicity concerns are mostly irrelevant.
According to Bruce Gibbins, founder of AcryMed Inc. (Portland, OR), silver doesn't interfere with the therapeutic properties of medical products. Gibbins, who manufactures wound dressings using antimicrobial silver, also explains that silver can be safely used even for patients who have diseases like diabetes that interfere with wound healing.
During the early 20th century, before the advent of antibiotics, silver was rediscovered as an antimicrobial agent from ancient times. However, use of metallic silver had inherent problems. Metallic silver can stain tissues and interfere with wound assessment. It also has a short shelf life requiring frequent reapplications to provide continuous antimicrobial activity. Metallic silver is biologically inert and passes through the body. In order to exhibit antimicrobial effects, silver must be in an ionic state. Ionic silver is a single atom missing one orbital electron. The antimicrobial character requires water to activate. Today, the use of silver oxide rather than metallic silver has eliminated these problems. However, application issues continue to emerge, and manufacturers continue to look for better techniques.
This article examines the benefits and limits of several processes for silver antimicrobial technologies. It also provides an overview of ionic plasma deposition (IPD), a technique that uses nanotech engineering for silver application.
Current Silver Antimicrobial Technologies
Research literature suggests that the most effective antimicrobial coating should be an integral part of the medical device surface.4 Manufacturers currently use at least four methods for applying silver oxide antimicrobial technologies. These methods include the following:
• Traditional coating technologies.
• Surface treatments by silver in hydrogel.
• Silver ion incorporation into material
• Surface-engineered nanostructures.
Each of these categories attempts to address the problems inherent in silver oxide antimicrobial applications with varying results.
Traditional Coating Technologies. For this method, a silver ion coating is applied by dip or paint to inhibit infections in invasive medical devices and to create burn and wound treatments. The device must be properly prepared first through sterilization and removal of debris before any coating process is performed. This traditional coating method has worked well, and several companies have proprietary application methods using nano-sized silver crystals for wound treatments. Devices and wound dressings treated with silver must be able to withstand the high heat associated with coating technologies. For example, certain coating technologies, such as plating, could not be used to apply silver oxide to a gauze bandage or disposable diaper—the fabric would disintegrate.
Another difficulty is observed when silver is used in conjunction with certain surfaces or coatings. For example, many medical devices, such as catheters, are manufactured with a hydrophobic polymer matrix, which limits the silver ion concentration near the device surface. Silver oxide requires the presence of moisture to release its anti-microbial properties. Affixing silver oxide to a hydrophobic polymer reduces the moisture pres-ent and thus decreases silver's antimicrobial effect. Commercially available devices coated with these processes may experience limited effectiveness.4
Hydrogel Polymer Systems. Silver ions need more surface-area exposure to maximize interaction with moisture on a medical device surface. Products that address this problem incorporate a nonreactive hydrogel polymer system to draw moisture and foster the release of the silver oxide. The hydrogel polymer also creates a greater surface area for silver diffusion from the coating and, therefore, a greater concentration of silver ions at the surface of the device.
Hydrogel technologies use a reservoir system of ionic silver, usually in the form of silver salt. The silver salt's release is controlled to provide antimicrobial activity without disrupting the body's production of cells required during the healing process.
One study indicated that the hydrogel silver fights infection in Foley (urinary) catheters, and the researcher called for double-blind, prospective controlled studies.5 And a small evaluation study indicated that using the hydrogel silver in urinary catheters had varying cost benefits and significant efficacy.6 Some hydrogel products offer lubricity as part of their hydrogel coating, in addition to antimicrobial silver.7
Modified Compound Polymers. Manufacturers are also working to extend silver antimicrobial effectiveness through modified compound polymers. Products called silver-antimicrobial compounds address this problem by adding silver mixed with a ceramic, such as zirconium phosphate, directly into the polymer material before it is manufactured into a medical device.
These so-called iontophoric polymers are designed to release silver ions when wet with body fluids. When the composite material comes in contact with or is immersed in an electrolytic fluid (such as saline, blood, drug preparations, or urine) the metal powders become a mass of tiny electrodes. Each molecule becomes an anode or a cathode, making the polymer conductive, which causes it to release the silver ions. The ion exchange is a slow process, which is a benefit because it may extend the antimicrobial effect.8 This application technique has been used in catheters. Other uses being explored include orthopedic implants, pacemaker leads, suture leads, and feeding tubes.
Ordered Nanostructures. The newest innovation for silver oxide antimicrobials involves surface-engineered ordered nanostructures of silver oxide that are built on the medical device surface. The approach employs nanotechnology to apply antimicrobial silver to medical devices.
Nanotechnology may provide the most effective platform to maximize the antimicrobial capability of silver. The nanostructures comprise silver particles. Because each tiny particle in a nanostructure has its own surface area, it increases the overall surface area of the silver oxide. A larger surface area means more silver can interact with body fluids to encounter and inhibit microbes.
Surface engineering of ordered nanostructures takes place on the nanometer scale. A nanometer is one billionth of a meter. To get an idea of scale, prick your finger with a pin. The diameter of that pinprick is a million nanometers.
IPD Surface Processing
One way to process nano-sized silver particles is through ionic plasma deposition (IPD) processing. Broadly speaking, IPD works with molecules smaller than 100 nanometers. The process creates a surface-engineered ordered silver nanostructure by first creating a vacuum to remove all contaminants. High kinetic energies that average 200 eV guide the charged silver ions or plasma to the surface of the medical device. The process runs at ambient temperature and can be supercooled when required, enabling a wide choice of materials. Temperature-sensitive materials such as gauze, paper, plastics, and synthetic fibers can be treated with the silver process.
The thermodynamic effects that are often associated with poor adhesion are controlled in the plasma rather than on the substrate. Depositing material ions are accelerated to ensure that the depositing species are the correct energy for the desired process and for the medical device polymer material. This allows for a broad range of custom stoichiometries and demonstrates that IPD technology is adaptable when used to treat medical polymers. Low-temperature polymers are used in soft-tissue implants. These polymers, such as polyethylene, polyester, polypropylene, and even Teflon (PTFE), can be treated with IPD nanotechnology.
IPD can be controlled for particle size, density, and rate of deposition. Because it incorporates a high degree of control and low heat application, IPD also has traits of adhesion and repeatability for silver application. The structures are laid down in a highly ordered surface. Deposition is possible in concentric plasma to almost any length. Source-material use is very efficient, so that high-volume precious-metal applications such as silver, platinum, and gold are economical.
Silver oxide application should maintain conformal quality of the medical device surface regardless of surface morphology. During the IPD process, the silver is deposited into blind holes, vias, and cavities with aspect ratios of 5:1.
Coatings are now measured in angstroms, and application layers must be extremely thin.9 IPD surface-engineered nanotechnology has ultra-thin-film capability, which can be used to treat flexible, porous materials such as antimicrobial bandages.
Finally, control of the dispersion of catalytic, conductive, and dielectric materials allows creation of new nanostructures. The materials are dispersed onto the substrate in precise formation. Large-scale production of medical devices is thus enabled. Nanostructures are combined with pure materials for catalytic structures, antimicrobial applications, filtration, and biomedical sensors. Tuning reaction and longevity, which can be varied depending on the requirements of the application, are highly desirable characteristics.
IPD Beyond Silver
Achieving hardness, corrosion resistance, and lubricity are problems in applications that include surgical tools and prosthetics such as hip implants. These characteristics may also be attained through surface-engineered nanotechnology. According to Jose LaManna, using IPD nanotechnology on surgical tools with interior moving parts can eliminate wear and heat resistance problems without changing the surface dimensions of these high-precision instruments. LaManna is senior R&D engineer for Anspach (Palm Beach Gardens, FL).
Many healthcare-acquired infections are the result of pathogens that are resistant to antibodies. The nature of silver and its antimicrobial effects make it an attractive material for medical device use. A number of options are available for applying silver antimicrobial technologies. Application processes continue to become more sophisticated, enabling optimal ion release and longer-lasting effects.
It is important to remember that nanotech silver does not eliminate infection-associated complications, but it may reduce the risk of such occurrences. Silver-modified medical devices may still give way to infection at some point in time. Detailed bacterial adhesion and biofilm studies are still required to prove coating efficacy.
The author would like to thank John Petersen, vice president and founder of Ionic Fusion Corp. (Longmont, CO) for his expertise and advice.
1. RP Wenzel and MB Edmond, “The Impact of Hospital-Acquired Bloodstream Infections,” Emerging Infectious Diseases (Atlanta: Centers for Disease Control, March/April, 2001); available from Internet: www.cdc.gov/ncidod/EID/index.htm.
2. Larry M Bush, “Disposable Items Help Prevent Healthcare-Acquired Infections,” Infection Control Today (Phoenix: Virgo Publishing, March 2005); available from Internet: www.infectioncontroltoday.com.
3. Robyn Mosher, “Silver: Metal of Many Faces,” Dartmouth Toxic Metals Research Program (Hanover, NH: Center for Environmental Health Sciences at Dartmouth, 2001); available from Internet: www.dartmouth.edu/~toxmetal/TXSHag.shtml.
4. Kelly M Pyrek, “Emergency Medicine Poses Challenges to Infection Control,” Infection Control Today (Phoenix: Virgo
Publishing, September 2002); available from Internet: www.infectioncontroltoday.com.
5. RA Bologna et al., “Hydrogel/Silver Ion–Coated Urinary Catheter Reduces Nosocomial Urinary Tract Infection Rates in Intensive Care Unit Patients: A Multicenter Study,” Urology 54, no. 6 (1999): 982–987.
6. ME Rupp et al., “Effect of Silver-Coated Urinary Catheters: Efficacy, Cost-Effectiveness, and Antimicrobial Resistance,” American Journal of Infection Control 32, no. 8 (2004): 445–450.
7. Sophie Bobin-Dubreaux, “Testing Laboratory Prevention of Bacterial Adhesion to Medical Polymers,” in NAMSA Authored Papers (BioMatech NAMSA; Chasse-sur-Rhone, France, September 1, 2001); available from Internet: www.namsa.com/advisor/articles.asp.
8. Katherine Simpson, “Using Silver to Fight Microbial Attack,” Plastic Adhesives and Compounding (Oxford, UK: Elsevier Advanced Technology, November 17, 2003).
9. Erik Swain, “Coatings: The Next Generation,” Medical Device & Diagnostic Industry 26, no. 7 (2004): 70–77.
David Tobler is the managing director of Nexxion Corp., a subsidiary of Ionic Fusion Corp. (Longmont, CO). Lenna Warner is vice president and principal at Mamalu Partners Inc. (Palm Beach, FL), a media relations com-pany specializing in nanotechnology.
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