May 10, 2023 | Researchers in Sweden who previously introduced a hydrogel wound dressing constructed of nanocellulose that requires no changing have further improved on their innovation with the integration of a pH sensor to passively monitor for early signs of infection. In parallel, they’re working on antimicrobial substances based on lipopeptides that are showing potency against multiple types of bacteria, according to Daniel Aili, professor in the division of biophysics and bioengineering at Linköping University.
The agenda here is to transform wound care by creating efficiencies for caregivers and better outcomes for patients while reducing the unnecessary use of antibiotics. In a study published recently in Materials Today Bio (DOI: 10.1016/j.mtbio.2023.100574), the nanocomposites demonstrated excellent wound dressing properties and the sensor was shown to rapidly produce a naked-eye readout of wound pH. Infection typically results in a change in wound pH, which is indicated by a color shift in the dressing from yellow to blue. The elevated pH value in the wound can be detected long before common signs of infection such as pus, soreness, and redness.
The tight-knit nanocellulose prevents bacteria and other microbes from getting in, but allows gases and liquid through, Aili explains. S2Medical, a Swedish wound care company, invented the dressing and is enabling academic investigators to have direct contact with patients to better translate products to the clinic.
Detection and management of infection in chronic wounds—those that have not healed within six weeks to three months or are recurring—is particularly important, as they are taking a heavy and growing toll on healthcare systems and patients the world over, he says. These hard-to-heal wounds represent about half of all costs in outpatient care.
“Most people know someone who has a chronic wound,” says Aili. “It is way bigger than cancer when it comes to how many people are affected by wounds.” In the U.S., between 3% and 4% of the population 65 and older have open wounds and many of them have underlying conditions such as diabetes and vascular disease. Prolonged hospital stays, and the required wound dressing changes, also exacerbate patient suffering.
The way chronic wounds are treated, which hasn’t changed in any significant way for decades, is part of the problem, he says. The focus has been on managing wounds to ensure they don’t get worse, rather than on healing them, which requires a holistic approach that includes improved wound diagnostic strategies.
Many different scientific fields have come together for the research underway at Linköping University, says Aili, which is being done in collaboration with colleagues from Örebro and Luleå Universities. These include molecular materials, nanotechnology, disaster and cardiovascular medicine.
Antibiotics are used extensively in wound care and the targeted pathogens typically are (or become) resistant to treatment, often with catastrophic consequences, Aili shares. Regular wound debridement, to remove dead tissue, is commonly done to prevent infection. Irrigation with antiseptics is also done to prevent or treat emerging infections.
“Of course, the earlier you detect and treat an infection .. the better possibilities you have to reduce infection and get rid of it,” says Aili. But to do so the conventional way requires a trip to the doctor’s office about every two days for a dressing change, and an assessment of the wound, which is both painful and inconvenient for patients. The dressing change process itself disturbs wound healing, and the risk of infection also increases every time the wound is exposed.
The nanocellulose-based dressings are essentially integrated into the tissue during the healing phase and spontaneously fall off with the scab, he continues, but “this only works if you don’t get an infection during this process.” The new dressing is designed to stay in place during the entire healing process and report suspicions of infection. It doesn’t break down because the body has no endogenous enzymes that degrade cellulose.
A dye known as bromothymol blue is used to make the wound dressing change color when the pH value exceeds 7. It gets loaded onto a silica material with nanometer-sized pores before being combined with the dressing material.
Biomarker-wise, the device is quite simple as instruments for measuring pH have been around for nearly a century. In fact, wound pH can in principle be measured using litmus paper strips at the same time dressings are being changed, Aili points out.
But even with optimized treatment, he adds, chronic wounds heal very slowly—a median of more than 40 days, based on a previous case study. The pH-responsive nanocomposites “can stay on as long as needed.”
Wound care in general is an enormously complex field, Aili says. All wounds are unique, and should patients develop an infection despite seemingly perfect care, they are automatically at risk of it not healing. Physicians, understandably, also need evidence that a medical device has been properly evaluated according to regulatory guidelines before they adopt it in their clinical practice.
Among other projects underway are further development of the wound dressing from a different source of cellulose, reports Aili. Researchers have also synthesized a promising anti-microbial substance in the lab that they are currently working to integrate into the device but can be used on its own. The small, protein-like peptides have been lipidated with a tiny hydrophobic moiety to ramp up their potency, he says.
Regulatory obligations for bringing a medical device to market can take five to 10 years, Aili notes. The research team is currently testing all the components of its newfangled wound dressing, alone and in combination, with the first clinical trials expected to begin within the next two years.