Keeping tabs

Wound care has become a multi-billiondollar problem that continues to impose a substantial financial burden on global society – not to mention a strain on the time and resources of clinical staff. Typical wound healing follows a specific sequence of events, starting with the initial injury and ending with closure. The steps within that sequence include clotting, inflammation, proliferation, and remodelling. But unfortunately, many patients have comorbidities that inhibit routine healing, such as advanced age, diabetes, peripheral vascular disease, inhibition of immune response, and venous insufficiency. The result of this is that a significant portion of wound care patients don’t make it past the inflammation stage of the healing sequence, and the acute wounds become chronic, making them susceptible to infection and other complications.

Patients with chronic wounds experience severe pain, social isolation, and significant emotional and physical distress. They often face months of treatments and exhaustive interventions that don’t lead to healing, but instead end with limb amputation, or worse, death.

As the incidence of chronic wounds continues to surge with the increasing elderly population and a sharp rise in obesity and diabetes, conventional strategies can’t keep up. Luckily, teams of researchers across the globe are looking for ways to use advances in technology to improve the care pathway for wounds.

Emerging technologies

One such example is the PETAL patch – a product born of extensive research from the National University of Singapore (NUS). A team of scientists at NUS developed the experimental PETAL patch dressing to continuously monitor a wound’s state of healing, without needing a power source to do so.

“The PETAL patch is a specially designed flexible patch made out of paper, within which we incorporated sensors to measure five biomarkers in wound fluids that can indicate whether a wound is healing properly or not,” says Benjamin Tee, associate professor at the Department of Materials Science and Engineering at the NUS College of Design and Engineering and the Institute for Health Innovation & Technology.

Tee, who led the research, explains that currently, clinicians swab a wound and send it to the lab for culture to assess its healing status. But dressing removal and swabbing are often painful and require additional time and resources to provide the information needed to proceed with proper interventions that promote healing. The PETAL (Paper-like Battery-free In situ AI-enabled Multiplexed) patch essentially does the swab and lab analysis by collecting the wound fluid into its fivepetalled flower panel, and using a proprietary deep learning algorithm, it assesses the status of the wound through its biomarkers within fifteen minutes. The PETAL patch has multiple layers: The bottom layer is a medical tape that adheres to the skin, there’s a middle fluidic panel layer arranged in a fivepetalled flower panel that collects wound fluid and a breathable top layer made of transparent silicone.

Once applied to a wound, the patch collects fluid through an opening in the petal-shaped fluid panel and distributes it throughout the five channels. Once inside the channels, it can sense five different biomarkers, including pH, temperature, uric acid, moisture, and trimethylamine (TMA). These carefully selected markers help assess wound inflammation, infection, and the overall wound environment.

“We chose these five biomarkers because they were the most relevant to wound healing for burn wounds,” says Tee. “We can change the number and type of biomarkers depending on the type of wound.”

The patch doesn’t need a battery or external power source; it is simply a piece of paper that, Tee expects, will eventually be designed into bandages where the sensor material will change colour. The patient or clinician will be able to use a smartphone to capture the sensor images, and the AI algorithm will quickly and accurately determine the healing status of the wound.

“We hope to increase biomarkers and improve our AI algorithm with even higher accuracy in tracing the wound-healing status, to enable earlier wound interventions so patients can recover without any scars,” says Tee. “The next steps are human studies, and we would love to extend the technology beyond burn wounds to different types of chronic wounds since they often lead to poor outcomes.”

Regarding production and cost, Tee believes the PETAL patch will be much more cost-effective than other products that need batteries or other electronics. “The patch and biomarkers are fairly scalable and we think it should be no more than the typical cost of a regular bandage,” he says. “The software would take some of the cost, but it too is scalable because it is just an application.” Tee and his team have filed an international patent for the PETAL patch and plan to advance to human clinical trials.

Wireless Smart Bandage

On the North American continent – more specifically in the state of New Jersey – Simiao Niu, assistant professor at the Department of Biomedical Engineering at Rutgers University is part of a team not just aiming to monitor chronic wounds, but treat them too – all using a single device. He explains that the traditional standard-of-care approach to wounds consists of a plain dressing meant to passively heal by keeping the area covered and safe from bacteria and infection. “But passive wound dressings don’t work for chronic wounds,” Niu adds. “Because once you have issues like diabetes, the wound will not heal naturally.”

To overcome this issue and integrate active treatment into the care pathway, Niu and colleagues designed a smart bandage that addresses the many challenges of chronic, non-healing wounds. It does this through multimodal sensors and electronic stimulators, allowing the technology to monitor and treat wounds without constant clinical intervention.

Electrical stimulation, also known as galvanotaxis, promotes healing by hastening the movement of keratinocytes to the wound, limiting bacterial growth on its surface, and promoting tissue growth and repair.

Niu believes traditional bandages incorporating wired electrical stimulation for wound healing have three important limitations. The wired design prevents patients from moving comfortably, they can stimulate the wound, but have no sensing capabilities, and finally, they impair the bandage-toskin interface. “These three limitations inspired us to design our smart bandage,” said Niu. “We designed a fully wireless, battery-free bandage for better patient comfort and mobility. The bandage utilises a closed-loop design with an AI algorithm that can sense and stimulate, and we designed a better bandage-to-skin interface that uses hydrogel to adhere the flexible circuit board to the skin.”

The result is a wireless, closed-loop, smart bandage that accelerates healing by accurately sensing the state of a wound and sending the correct amount of electrical stimulation to reduce infection and promote healthy skin restoration.

“Once the sensing circuit senses skin impedance, we have software that automatically analyses the sensor and emits the right amount of power to stimulate the wound.” The wireless smart bandage circuitry is a scant 100 microns thick and incorporates a microcontroller unit, radio antenna, memory, electrical stimulator, and biosensors that sit on a rubbery patch. A hydrogel seal adheres the bandage securely to the wound surface.

“The hydrogel seal is imperative to proper wound healing,” Niu explains. “We needed good skin adhesion, but if it is too good, it will harm the healing skin underneath when removed. At normal body temperature, the adhesion is excellent, but if we slightly increase the hydrogel temperature to about 48 degrees, it can be removed safely without harming the skin.”

The bandage and circuitry can be removed and reapplied for practical use in the clinical setting. “The only thing that would need changing is the hydrogel; the patch and its circuitry are completely reusable.” Just like the team behind PETAL, Niu and his Rutgers colleagues have considered the affordability of the device, and they believe it will be cost-effective for hospitals. “We calculated the cost for each smart bandage, and even without mass production, at the lab level, one smart bandage costs about $15-$20 for the circuit board, and for the hydrogel, it’s even cheaper.”

The PETAL patch and the wireless smart bandage are innovative, proof-of-concept designs. Researchers admit that more work must be done, specifically with expanding and perfecting the AI algorithms associated with the dressings. Even so, both provide a snapshot of the innovation that is now possible with the state of technology. Whether either device has the potential to make the journey out of the lab and into the clinic will likely be determined once they reach the stage of human clinical trials. But if that potential includes dramatically transforming how clinicians monitor and treat chronic wounds at a cost that is not prohibitive, it is surely worth finding out.