Use of Copper Nanoparticles to Reduce Bioburden in the Treatment of Diabetic Foot Ulcers

A 63-year-old white man who has diabetes mellitus type 2 and coronary artery disease presented with a diabetic foot ulcer (DFU) on the plantar aspect of the left foot (Figure 1). The wound was first noted 11 months ago. Treatments with a 2-layer antibacterial dressing embedded with copper oxide (MedCu Technologies) was applied to the DFU and replaced daily. The subject was instructed to follow up on a weekly basis. 

On examination after 8 weeks of treatment, the effects of the copper nanoparticle-infused dressing on both wound size reduction and bioburden reduction were observed (Figure 2). The wound surface area decreased by 63% from baseline, and bacterial flora in the wound bed were also significantly reduced. Treatment with the copper-infused dressings was continued, and on repeat examination 3 months later, the wound was considered healed (Figure 3).

A person with diabetes has a risk of developing a DFU of approximately 14%.¹ In addition, ulcer recurrence is extremely high: 40% within the first year of healing and up to 65% within 5 years.¹ Standard of care for chronic DFUs encompasses removing necrotic tissue, preventing wound infection and sepsis, and correcting ischemia (if present). Interdisciplinary management of the disease process, including annual podiatric assessments, should be a mainstay in treatment. A DFU can become a chronic issue that may require nontraumatic amputation if poorly managed. Patients with diabetes who undergo nontraumatic amputation due to a nonhealing DFU have a 5-year postamputation mortality of nearly 45%.² 

The ideal adjunct therapy for a nonhealing DFU should have antibacterial properties and aid in the rapid closure of the wound while being cost-effective and nontoxic. Copper nanoparticle–infused dressings have potential as an adjunct therapy due to their antimicrobial properties.³ Copper nanoparticles have increased cellular uptake due to their small size, high surface area, and shape.⁴ These nanoparticles also have multiple antimicrobial mechanisms that take place both intra- and extracellularly. Copper permanently alters the structure of bacterial and viral proteins, induces oxidative stress that inactivate viruses, and causes the peroxidation of lipids, leading to cellular death.^5-7 Finally, studies have also shown that copper nanoparticles increase expression of both hypoxia-inducible factor and vascular endothelial growth factor to promote angiogenesis in wounds.⁴

Offloading (the reduction of pressure on the affected area) is the first-line treatment for DFUs in addition to wound hygiene and proper dressing management. Wound healing should be assessed weekly. It has been demonstrated that 50% wound area reduction by the fourth week is predictive of complete wound healing by week 12.⁸ Therefore, in cases where less-than-optimal wound healing is noted after the first 4 weeks, practitioners should look to use more advanced wound healing modalities to expedite the healing process. Hyperbaric oxygen therapy as a treatment for DFUs has been used with success for decades. While the exact mechanism through which it affects wound healing is still not fully understood, it is thought to improve neovascularization and decrease inflammatory responses, leading to overall improved wound healing. In cases where basic wound dressings and other modalities are not successful in achieving timely healing of ulcers, cellular tissue-based products (CTP) should be considered. CTPs aid in wound healing through multiple ways, including and not limited to maintaining moisture balance, providing structural support for tissue regeneration, producing anti-inflammatory effects, and bringing cytokines and growth factors to the wound base to promote granulation.

Preventing and eliminating infections in the setting of DFU are very important to prevent further limb loss. Proper wound examination should include examining the wound for any signs of active infection, including but not limited to erythema, edema, warmth, and presence of purulent discharge. The absence of all of these signs should exclude clinical infection, whereas the presence of any of them increases the likelihood of active infection and triggers the need for further workup through imaging and obtaining the appropriate lab studies to assess for the presence of infection. DFU infections are often polymicrobial, and the flora can be dependent on severity of the wound.⁹ Superficial infections are most likely caused by gram-positive cocci (eg, Staphylococcus aureus, S agalactiae, S pyogenes). Deeper wounds with more extensive involvement tend to be predominantly colonized by Pseudomonas aeruginosa and anaerobes. Of note, methicillin-resistant S aureus (MRSA) infections can be seen in persons with DFU, especially those with history of MRSA. In cases where infection is noted to be present, timely management with antibiotics and local incision and drainage where warranted is paramount and should be performed based on the latest Infectious Disease Society of America (IDSA) guidelines.¹⁰ 

This case shows that copper nanoparticle–infused dressings have the potential to be a powerful adjunct to the current standards of care for recalcitrant DFUs because they reduce the bioburden of the flora in the wound and have been shown to markedly reduce wound size.

Affiliations: ¹Donald & Barbara School of Medicine at Hofstra/Northwell, Hempstead, NY; ²Northwell Health Comprehensive Wound Healing Center & Hyperbarics, Lake Success, NY; ³Northwell Health Department of Surgery, Podiatry Section, NY

Correspondence: Alisha Oropallo, MD; aoropallo@northwell.edu

Disclosures: The authors disclose no relevant financial or nonfinancial interests.