The wound care arena of the 21st century offers the practicing clinician a wide array of products and technologies to utilize in the management of diabetic foot ulcerations. Our patients are benefitting from the explosion of emerging technologies and evidence-based algorithms are helpful in guiding treatment interventions. Some technologies are innovative and a reflection of modern discoveries while others like medicinal applications for copper were in use in ancient times.
Copper has been used for centuries as a disinfectant of fluids, solids and tissues. It is known to have both natural antibacterial and antifungal properties. Constant exposure to high copper concentrations is toxic to microorganisms yet resistance is extremely rare. There are several theories given for the potent biocidal activity of copper. These theories include: alteration of proteins and inhibition of their biological assembly and activity; plasma membrane permeabilization; and membrane lipid peroxidation.1
As a vital trace element, copper is known to be safe and tolerated by humans. The United States National Academy of Sciences Committee recommends a daily allowance of 0.9 mg of copper for normal adults. Common naturally occurring dietary resources of copper include vegetables, legumes, nuts, grains and fruits, as well as shellfish, avocado and beef. Given that copper is present in the earth’s crust, most of the world’s surface water and ground water used for drinking purposes contains small amounts of copper.
Copper is required for the normal function of many human tissues including skin and is postulated as an important cofactor in angiogenesis and wound repair. Copper is necessary (along with iron) for the formation of hemoglobin. It also plays a role in keeping bones, blood vessels and nerves healthy. Copper is involved in numerous biochemical reactions in human cells. Copper is a component of multiple enzymes. It is involved with the regulation of gene expression, mitochondrial function/cellular metabolism and connective tissue formation as well as the absorption, storage and metabolism of iron.2 Copper levels are tightly regulated in the body.
Copper toxicity is extremely rare in the general population. Wilson’s disease is a genetic disorder in which the body cannot rid itself of copper. This results in copper deposition in organs and serious consequences such as liver failure and neurologic damage.
While there is a lack of concrete evidence to prove the efficacy of copper for several conditions, there is substantial anecdotal experience that warrants further research. The use of copper bracelets in the treatment of arthritis has a long history. There are research reports suggesting that copper salicylate may reduce arthritis symptoms more effectively than either copper or aspirin alone.3
Other medical conditions possibly associated with the therapeutic use of copper include macular degeneration, Alzheimer’s disease, schizophrenia, osteoporosis and even cosmetically in skin rejuvenation. However, copper has been used for years. It is well tolerated for prolonged and widespread human use as exemplified by female use of copper intrauterine devices (IUDs).
In an animal model, Borkow and colleagues studied the safety and biocidal properties of a non-stick dressing containing copper oxide particles.4 Recognizing the potent antimicrobial activity of copper, its role in the wound healing cascade and demonstrated low skin irritation, the authors hypothesized that Band-Aids containing copper would not only prevent wound contamination, but also promote wound healing.
The researchers utilized a partial thickness porcine wound model for the study.4 They created 12 deep punch biopsy wounds (12 mm x 5 mm in diameter). They treated six of the wounds with the copper test dressing and the other six wounds with control commercial dressings. The study authors performed macro- and microscopic evaluations, and recorded results at day three and day seven after the wounds were created. Researchers concluded that the test dressing demonstrated a high broad-spectrum biocidal efficacy and was well tolerated without significant adverse event.
In a pilot in vivo study involving 56 patients, Zatcoff and co-workers found that the use of copper soled socks facilitated improvement in the common manifestations of tinea pedis including erythema, scaling, fissuring, burning, itching and vesicular eruptions.5 The study authors noted that no patients worsened or showed adverse reactions while wearing copper-oxide impregnated socks.
Currently, there is technology that incorporates copper oxide in the manufacturing process of textiles such as socks. Given the demonstrated antimicrobial, antifungal and antiviral benchwork studies that researchers have done, introducing copper into fabrics may have significant clinical ramifications.
Based on the strong in vitro data and some in vivo data, the Miami VA Healthcare System is currently involved in an IRB-approved multicenter study to provide evidence-based medicine on the possible efficacy and safety of using copper oxide impregnated socks as a preventative measure for diabetes-related lower limb and foot ulcers.
Copper oxide may be easily incorporated into textiles such as socks as well as dressings. Copper oxide is the most naturally occurring and abundant form of copper available. Being a non-soluble compound, it allows a slow and steady release of copper in the presence of humidity and moisture, which is ideal for use in socks. Researchers have hypothesized that the antimicrobial and antifungal properties of the copper socks may decrease the incidence of itching. They may also help prevent cracks and fissures that may be part of the causal pathway leading from ulceration to secondary infection, and even amputation in the high-risk diabetic population.6 In the presence of peripheral neuropathy and vascular disease, often a simple skin breakdown or irritation can result in limb-threatening infections.
In addition to exploring the use of copper textiles in the medical community, we have also seen the incorporation of copper textiles into the military sector. When copper technology is integrated into military clothing and footwear, it offers the additional potential antimicrobial and antifungal benefits as well as an improvement to skin appearance to those serving in the military. Veterans of the armed services throughout the world are exposed to harsh weather conditions and moisture immersion, and often do not have the ability to change footwear regularly.
Cupron Medical produces copper infused socks and was recently selected by the Israel Defense Forces to supply antimicrobial socks. With this selection, the Israel Defense Forces became the first army in the world to supply its soldiers with antimicrobial socks based on the innovative copper-based technology.
There are exciting laboratory bench work studies currently being conducted to explore the scientific role copper may play in wound healing processes such as angiogenesis. Studies are also looking at the bactericidal and fungicidal properties of the element. There are also clinical studies such as our multicenter study that are exploring the preventive aspect and application of copper impregnated textiles.
Why not add copper oxide to socks if there may be a strong prevention aspect? Could wound biopsies prove low local levels of copper that impair wound healing? Could supplementation with topical copper (and in what form) facilitate wound closure? The bridge between basic science and clinical relevance will hopefully prove to be beneficial for our high-risk patients in the near future.
Dr. Rothenberg is the Director of Residency Training and is an Attending Podiatrist with the Miami Veterans Affairs Healthcare System.
1. Borkow G, Gabbay J. Putting copper into action: copper-impregnated products with potent biocidal activities. FASEB J. 2004;18(14):1728-30.
2. Philips N, Hwang H, Chauhan S, Leonardi D, Gonzalez S. Stimulation of cell proliferation and expression of matrixmetalloproteinase-1 and interleukin-8 genes in dermal fibroblasts by copper. Connect Tissue Res. 2010;51(3):224-9.
3. Mehtar S, Wiid I, Todorov SD. The antimicrobial activity of copper and copper alloys against nosocomial pathogens and Mycobacterium tuberculosis isolated from healthcare facilities in the Western Cape: an in-vitro study. J Hosp Infect. 2008;68(1):45-51
4. Borkow G, Gabbay J, Dardik R, et al. Molecular mechanisms of enhanced wound healing by copper oxide impregnated dressings. Wound Repair Regen. 2010;18(2):266-75.
5. Zatcoff R, Smith M, Borkow G. Treatment of tinea pedis with socks containing copper-oxide impregnated fibers. Foot (Edinb). 2008;18(3):136-41.
6. Borkow G, Zatcoff RC, Gabbay J. Reducing the risk of skin pathologies in diabetics by using copper impregnated socks. Med Hypotheses. 2009;73(6):883-6.