Authors: Tim Sandle
Dressings are long-established in the medical field for keeping wounds clean and preventing secondary infections. Dressings are essential for reducing infection risk; more recent advancements have seen dressings developed to promote wound healing.
Wound healing refers to a specific biological process related to the general phenomenon of growth and tissue regeneration. Wounds heal by the control of moisture and by a process of staving off infection; while dressings have addressed the former over centuries, with the latter specialized dressings are being developed. Dressings to aid wound healing have been used for several decades, such as the use of hydrocolloid dressings to help treat burns and with the application of hydrogels for wounds that are leaking little or no fluid. However, it is in more recent years that antimicrobial compounds have been incorporated.
This involves the addition of physical or chemical processes designed to kill any pathogenic microorganisms that might be present, and which pose a risk of triggering a disease such as sepsis (where the chemicals that body’s immune system releases into the bloodstream to combat an infection trigger inflammation throughout the entire body) or delay the rate of wound healing (one of the causes of delayed wound healing is the presence of microorganisms in the wound). This article examines some of these developments, and also considers an additional development in the form of color-changing dressings for signaling the presence of antimicrobial-resistant bacteria.
In recent years, dressings have been developed with the addition of antimicrobial coatings. Antimicrobial coatings work in multiple ways to prevent infections from spreading. These are:
- The chemical properties embedded within the coating kill the most common types of bacteria, including those that are known to be antibiotic resistant.
- The coating makes the dressing material super-absorbent and pulls excess moisture away from the wound (many microorganisms require moisture in order to multiply).
- The microbial coating creates a barrier and blocks bacteria from reaching a wound and recolonizing there.
The first wave of antimicrobial dressings employed silver and alginates, and silver compounds remain the most common agents in-use (typically as either silver alginate or silver carboxymethylcellulose). Silver has established antimicrobial properties and is a broad-spectrum agent: it is bactericidal to a large number of Gram-positive and Gram-negative microorganisms, many aerobes and anaerobes and several antibiotic-resistant strains.
Silver dressings work well in terms of microbial toxicity and by providing a barrier, where more recent research is with the application of silver nanoparticles. However, silver-impregnated dressings can also release ions that can allow resistance to develop, thereby leaving the wound susceptible to certain types of bacterial infection. This is leading to the application of alternative antimicrobials, such as polyhexanide-containing biocellulose dressings or chitosan acetate preparations.
Applying electric fields
Faster wound healing can be achieved via enhanced fibroblast migration, proliferation and differentiation. Research suggests this acceleration can be induced by applying an electric field across a dressing formed from polytetrafluoroethylene, copper foil and polyethylene terephthalate.
Another application is with using electric fields to inhibit bacterial growth. One research stream is occurring at Ohio State University Wexner Medical Center (OH, USA) where scientists have been experimenting with the generation of weak electric fields that can disrupt bacterial biofilm infections at the site of a burn wound. Biofilms are communities of bacteria that have an added protection in the form of a ‘slime like’ layer, where the extracellular matrix promotes the adhesion of microorganisms to a surface and facilitates community growth and survival.
The electric field is generated as bodily fluids are produced (such as a weep from a wound), where the dressings are formulated to contain small silver and zinc dots arranged as a pattern of tiny batteries. The contact with liquid initiates the dressing to become active based on a wireless electroceutical process. This process does not require the application of external power.
Studies on pigs have demonstrated that where the dressing is applied within 2 hours of wound infection, the possibility of biofilm formation is significantly lowered. Over the course of 7 days scanning electron microscopic images, indicated significant reductions in bacterial communities.
An advantage with this type of application is with the potential to overcome antimicrobial resistance, which can develop where antimicrobials are used in dressings. The research has been published in the journal Annals of Surgery (“Electric field based dressing disrupts mixed-species bacterial biofilm infection and restores functional wound healing.”)
In a variation to the microbial killing approach, Iranian scientists have developed a novel compound, created using nanotechnology, for the treatment of wounds. This is with the use of a composite material containing antimicrobial chemicals.
The nanotechnology has been designed to enable improved mechanical, chemical, thermal and antimicrobial properties. For the experimental dressing, nanocellulose and antimicrobial zinc oxide nanoparticles have incorporated into a film. The film is composed of cellulosic material and the dressing has been designed for the slow release of the antimicrobial particles. The controlled-release mechanism is achieved through the use of three thin layers, each of which is stacked on top of the other.
The development of this dressing has been reported to the journal Carbohydrate Polymers, where the research paper is titled “Morphological, physical, antimicrobial and release properties of ZnO nanoparticles-loaded bacterial cellulose films.”
Sensing drug resistance with color-changing dressings
In addition to developing dressings with the capability of killing pathogenic organisms, research is progressing with color-changing dressings that can sense the presence of pathogens and then determine whether these pathogenic organisms are antimicrobial resistant. Receiving an earlier alert about the efficacy of an antimicrobial would enable a clinician to adopt an alternative treatment regime.
Reported in early 2020, Chinese scientists have produced a material that changes color (green to yellow) under conditions where an acidic microenvironment develops (as is the case where a bacterial infection forms). This triggers the chemicals incorporated into the dressing to release an antimicrobial compound that is formulated to kills bacteria.
Circumstances will arise where the infectious agent is resistant to the broad-spectrum antimicrobial incorporated into the dressing. In cases where drug-resistant bacteria are present, the dressing becomes red in color. This color change happens as the result of an enzyme released by the bacteria. As an example, it took 4 hours for the dressing to sense a population of 10,000 cells of drug-resistant Escherichia coli. This red coloration signals to a medic the likely presence of problematic organisms. The treatment step developed is for healthcare staff to apply a light at the dressing, which leads to the dressing to release reactive oxygen species designed to kill or inactivate the bacteria (a process referred to as Zr-MOF PCN-224-based photodynamic therapy). With the surviving-but-weakened bacteria, these organisms become more susceptible to the antimicrobial.
At present, the efficacy of the dressing has only been demonstrated in relation to wound created on mice under experimental conditions, where the rodents were purposefully infected with combinations of drug-sensitive and drug-resistant bacteria. Nevertheless, the results are sufficiently successful to lead to a further wave of testing and the perhaps the eventual development of a dressing that be used for patients.
The research has been published in the journal ACS Central Science, with the research paper titled “Colorimetric band-aids for point-of-care sensing and treating bacterial infection”.
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