Journal Articles

Effectiveness of nano-copper solution to reduce wound bioburden in chronic wounds: a case series

Share this article

Effectiveness of nano-copper solution to reduce wound bioburden in chronic wounds: a case series

Harikrishna KR Nair, Nor Azmi Bin Mohamad Kamal, Rosy Abdul Rashid, Tang Pui Ling
4 October 2023
Bacterial bioburden is a major factor that causes delayed wound healing in many hard-to-heal wounds, and has a direct impact on the patient and healthcare system. Copper is a potent trace element with antimicrobial properties and low toxicity, which is suitable to be used in wound management. Here we reported a case series that demonstrated the clinical effectiveness of nano-copper solution in reducing bacterial bioburden in chronic wounds. There were a total of 10 patients recruited in this case series, including venous leg ulcers (n=5), diabetic foot ulcers (n=4) and chronic hard-to-heal wounds (n=1). Bioburden parameters were assessed with MolecuLight pre- and post-wound cleansing with copper nanoparticles-infused solution (CuHEAL++). These studies showed a significant reduction in bacterial load after treatment with nano-copper solution that was used as a wound cleansing agent. No adverse side effects were reported. These results suggest that nano-copper solution is suitable as an antimicrobial wound cleansing solution, to reduce bacterial bioburden in wounds.

Silver (Ag) and Copper (Cu) were used in the time of the Persian monarchs for water disinfection and sanitisation, as well as for food preservation (Lemire et al, 2013). Silver foils have been used to prevent surgical wound infection, while copper compounds have been widely used in agriculture as fungicides on grapes and potatoes (Lemire et al, 2013). Copper was also prescribed for respiratory diseases and used for purifying water in ancient Greece (400BC; Dollwet and Sorenson, 2001). Copper was acknowledged as the first metal with antibacterial properties by the United States Environmental Protection Agency (US EPA) in 2008 (Pradot al, 2012). Copper is considerably cheaper and more easily accessible compared with silver and gold. However, the native form of copper ions is commonly converted into nanoparticles in order to optimise the efficacy of copper in wound healing (Tiwari et  al, 2014). Copper nanoparticles (CuNPs) have potentially enhanced catalytic activity and improved bioavailability in comparison to the native form (Tiwari et  al, 2014). In addition, copper nanoparticles that exhibit biocompatibility can be manufactured using eco-friendly processes. 

Nanotechnology is a novel therapy in wound management that incorporates nanometer-sized materials, with implications for tissue repair, regenerative health and disease prevention (Zarrintaj et al, 2017). In addition to healthcare or wound management, copper-based nanoparticles have also been used in various ways, including as an antimicrobial coating for dental hygiene and virus disinfection. The use of nanoparticles provide a new, alternative to aid the wound healing process. Furthermore, it has unique properties as a bactericidal agent (Barroso et al, 2020). 

In view of the antimicrobial abilities and low toxicity properties, metal nanoparticles comprised of copper, silver, gold and zinc are ideal for incorporation into wound dressings (Negut et al, 2018). Copper has a low level of resistance among microbes that are clinically significant, which is one of the key advantages of using it as a bactericidal agent. It also has a complex role in various tissue cells where it modulates various cytokines and growth factors that are an essential component in all stages of wound healing (Kornblatt et al, 2016) The bactericidal activity of copper is mainly attributed to the release of ions, which affects the integrity of the membrane and the bacterial cell wall, generates intracellular oxidative stress and is genotoxic, resulting in the death of microorganisms (Grass et al,  2010; Vincent et al, 2018). In general, CuNPs have a greater ability to engage and interact with the membrane of bacteria and subsequently compromise the structural integrity of bacterial membranes.  

Intact skin functions as a protective barrier that effectively prevents microbial invasion. Any break in the skin integrity and compromise to the epidermal barrier will facilitate bacteria to enter the deeper layers of the skin with a higher risk of infection. All open wounds are vulnerable to contamination and microbial colonisation, although not all contaminated wounds will develop an infection (International Wound Infection Institute, 2022). Microbial infection remains a major factor in delayed wound healing in chronic hard-to-heal  wounds. Other factors include hypoxia or poor perfusion; repetitive ischaemia-reperfusion injury; and inadequate offloading or compression therapy (Malone et al, 2017). The Wound Healing Society categorises chronic wounds into four different groups based on the causative aetiologies, which include pressure injury, diabetic foot ulcers (DFUs), venous leg ulcers (VLUs) and arterial insufficiency ulcer (Kirsner, 2016). 

Chronic wounds pose a significant global issue to the healthcare system because of their rising prevalence and substantial management costs. According to Gottrup et al (2004), it is estimated that 1–2 % of the population would suffer from a chronic wound during their lifetime in developed countries.

Biofilms play a significant role in impeding the process of wound healing and increasing susceptibility to wound infection, especially in the case of chronic wounds. Biofilms have been reported to be present in 60% (James et al, 2008) to 80% (Romling et al, 2012) of chronic wounds, and a recent meta-analysis suggests their presence is in at least 78.2% of chronic, hard-to-heal wounds (Malone et al, 2017). Therefore, early detection and identification of bioburden in wounds, and subsequent intervention to eradicate infection, is beneficial from both a clinical and economic aspect, thereby reduce burden on patients, caregivers and healthcare systems.  

This case study aims to establish the clinical effects of using the cleansing agent, copper nanoparticles-infused solution, containing 0.1% ionized copper, on bacterial burden in lower leg wounds.

Materials and methods

Patients were recruited and followed up at the Wound Care Unit, Hospital Kuala Lumpur. Random sampling of patients was done among patients with wounds at the lower extremity. A variety of clinical cases were included, such as DFUs, VLUs and chronic, hard-to-heal wounds. Wound assessment was completed using the T.I.M.E. framework and bioburden parameters were assessed with MolecuLight pre- and post- wound cleansing with copper nanoparticles-infused solution. 

MolecuLight is a non-invasive fluorescence imaging device (Figure 1) that is able to visualise both wound tissue and bacterial fluorescence. The application of an excitation light (405nm violet light) to the wound bed tissues results in the generation of a range of fluorescence signals, and is able to create a map of bacteria in the wound bed, which is used for targeted cleansing and debridement. This imaging device requires a dark environment; therefore, all wound photos were taken under an attachable drape without ambient light exposure, to avoid misinterpretation of fluorescence or false positive results. Table 1 shows how to interpret the different fluorescent signals.  

Each study subject received the same wound cleansing protocol and was followed by the standard wound treatment as practiced in the Wound Care Clinic, Hospital Kuala Lumpur.  

Wound cleansing protocol

  • All previous wound dressings were removed at the affected limb
  • Wound assessment was completed with the T.I.M.E. framework 
  • MolecuLight was used over the wound bed prior to wound cleansing to identify the level of wound bioburden
  • Wounds were rinsed and soaked with gauze containing copper nanoparticles-infused solution (CuHEAL++) for 10–15 minutes 
  • Wound bioburden was reassessed with MolecuLight after wound soaking and cleansing
  • All wounds were followed by a standard of wound management, with debridement and modern wound dressings.  

All patients were informed about the study, regarding the application of the nano-copper solution as the cleansing solution, and possibility of adverse effects of copper usage was explained.  Furthermore, the patients consented to the use of their data and images for publications and educational use.


There were a total of 10 patients with wounds of the lower extremities recruited in this study, five  VLUs, four DFUs and one chronic hard-to-heal wound. All wounds were assessed for bacterial bioburden pre-cleansing with nano-copper solution (CuHEAL++). MolecuLight imaging revealed positive findings in all cases and indicated a high level of bacterial bioburden in the wound bed and periwound skin area before wound cleansing.  

All fluorescence images captured before wound cleansing demonstrated mostly cyan fluorescence (denoted by yellow arrow in each case) at the wound edge or periwound in eight of the cases. The other two cases showed the presence of red florescence (denoted by the white arrows) in the wound bed and wound edge. 

These studies show that there is a reduction in bacterial load after using nano-copper solution as a wound cleansing agent, as evidenced by the MolecuLight fluorescence signals. Comparison between pre- and post-wound cleansing in all above clinical cases is shown in Case 1–10.  

No adverse side effects were reported by any of the patients. There were no reports of copper toxicity, or dermatologic sensitivity in all clinical cases. 


The essential aspect of wound healing involves identification and subsequent reduction or elimination of bacterial bioburden. Significant bacterial loads usually demand a bacterial-targeted wound treatment procedure, such as wound cleansing, debridement or the use of antimicrobial dressings to optimise the wound bed and facilitate wound healing (Edwards and Harding, 2004). Nanoparticles that have antimicrobial properties and low toxicity to cell tissues are ideal to be used in wound management, as a cleansing solution or dressing product (Pang et al, 2023). 

In the above case studies, we have shown the effectiveness of the copper nanoparticles infused solution in reducing wound bioburden over the wound bed and periwound skin area after soaking and cleansing the wound before standard wound care. Copper nanoparticles are well-recognised nanoparticles that have a broad-spectrum antimicrobial action (Sandoval et al, 2022). Copper biocidal effect is mediated through altering bacterial proteins, inhibiting the biological activity, permeabilisation of plasma membranes and membrane lipid peroxidation, which subsequently lead to bacteria cell death (Borkow and Gabbay, 2005). Besides, it also plays an important role in wound healing by promoting the development of extracellular matrix (ECM) components such as integrins, the key modifiers of cell attachment to the ECM, fibrinogen and collagen synthesis (Sandoval et al,  2022).  

Copper usage is relatively safe although it has a strong biocidal action, because it is an essential trace metal that is efficiently metabolised by the human body when absorbed through tissue in comparison to silver (Melamed et al, 2021). Therefore, copper is suitable to be used as an alternative to silver and as a wound cleansing solution or incorporated into a dressing to reduce biocontamination. 


First and foremost, this is an observational study with a limited number of clinical cases that are focused on wounds of the lower extremities. A more robust study with larger number of patients and comparison of numerous clinical cases involving other part of the body (including upper extremities, trunk, sacral and gluteal) with comparison to other antiseptic solutions may be useful to support the literature evidence and validate the study’s results. 

Secondly, MolecuLight has limited sensitivity in identifying wound bioburden, as it is only able to detect certain bacteria such as Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa

Lastly, our center does not routinely perform swab or tissue culture sampling for patients unless indicated. Therefore, there is no microbiological profile taken at the same settings, in comparison to the MolecuLight results, to confirm the presence of bacteria in the wound bed in this study. 


This case series demonstrated the clinical effectiveness and efficacy of nano-copper solution as an antimicrobial wound cleanser, which significantly reduces wound bioburden and promotes wound healing of chronic wounds. 

Disclaimer: The authors are sincerely thankful to the Wound Care Unit, Department of Internal Medicine, Hospital Kuala Lumpur for providing the necessary research facilities and data collection for this study.

Barroso A, Mestre H, Ascenso A et al (2020) Nanomaterials in wound healing: from material sciences to wound healing applications. Nano Select 1(5):443–60.

Borkow G, Gabbay J (2005) Copper as a biocidal tool. Curr Med Chem 12(18):2163–75.

Dollwet HHA, Sorenson JRJ (2001)Historic uses of copper compounds in medicine. Trace Elements Med 2:80–7

Edwards R. Harding KG (2004) Bacteria and wound healing. Curr Opin Infect Dis 17(2):91–6.

Gottrup F (2004) A specialized wound-healing center concept: importance of a multidisciplinary department structure and surgical treatment facilities in the treatment of chronic wounds. Am J Surg 187(5A):38S-43S. d

Grass G, Rensing C, Solioz M (2011) Metallic copper as an antimicrobial surface. Appl Environ Microbiol 77(5):1541–7.

International Wound Infection Institute (IWII) (2022) Wound infection in clinical practice: principles of best practice. Wounds International (accessed 17 September 2023)

James GA, Swogger E, Wolcott R et al (2008) Biofilms in chronic wounds.Wound Repair Regen16(1):37–44.

Kirsner RS (2016) The wound healing society chronic wound ulcer healing guidelines update of the 2006 guidelines–blending old with new. Wound Repair Regen 24(1):110-1.

Kornblatt AP, Nicoletti VG, Travaglia A (2016) The neglected role of copper ions in wound healing. J Inorg Biochem 161:1e8.

Lemire JA, Harrison JJ, Turner RJ (2013) Antimicrobial Activity of metals: mechanisms, molecular targets and applications. Nat Rev Microbiol 11(6):371−84.

Malone M, Bjarnsholt T, McBain A et al (2017) The prevalence of biofilms in chronic wounds: a systematic review and meta-analysis of published data. J Wound Care 26(1):20–5.

Melamed E, Kiambi P, Okoth D et al (2021). Healing of chronic wounds by copper oxide-impregnated wound dressings-case series. Medicina (Kaunas) 57(3):296.

Negut I, Grumezescu V, Grumezescu AM (2012 Treatment strategies for infected wounds. Molecules 23(9):2392.

Pang Q, Jiang Z, Wu K et al (2023) Nanomaterials-based wound dressing for advanced management of infected wound. Antibiotics (Basel) 12(2):351.

Prado J V, Vidal A R, Durán T C (2012) [Aplicación de la capacidad bactericida del cobre en la práctica médica]. [In Spanish] Rev Med Chil 140:1325–32.

Romling U, Balsalobre C (2012) Biofilm infections, their resilience to therapy and innovative treatment strategies. J Intern Med 272(6):541–61.

Sandoval C, Ríos G, Sepúlveda N et al (2022) Effectiveness of copper nanoparticles in wound healing process using in vivo and in vitro studies: a systematic review. Pharmaceutics 14(9):1838.

Tiwari M, Narayanan K, Thakar MB et al (2014)  Biosynthesis and wound healing activity of copper nanoparticles IET Nanobiotechnology 8(4):230-72.

Vincent M, Duval RE, Hartemann P, Engels-Deutsch M (2018) Contact killing and antimicrobial properties of copper. J Appl Microbiol 124(5):1032–46.

Zarrintaj P, Moghaddam AS, Manouchehri S et al (2017) Can regenerative medicine and nanotechnology combine to heal wounds? The search for the ideal wound dressing. Nanomedicine (Lond) 12(19):2403–22.

Free for all healthcare professionals

Sign up to the Wounds Group journals

By clicking ‘Subscribe’, you are agreeing that the Wounds Group are able to email you periodic newsletters. You may unsubscribe from these at any time. Your info is safe with us and we will never sell or trade your details. For information please review our privacy policy.

Are you a healthcare professional? This website is for healthcare professionals only. To continue, please confirm that you are a healthcare professional below.

We use cookies responsibly to ensure that we give you the best experience on our website. If you continue without changing your browser settings, we’ll assume that you are happy to receive all cookies on this website. Read about how we use cookies.

I am not a healthcare professional.