Certain wounds do not heal. Diseases like diabetes, infections, and suppressed immune systems frequently cause healing to slow down. Chronic wounds tend to last for months, and in the worst conditions, they can become life-threatening. Treatment cost has risen to $25 billion annually.
Drawing of wireless smart bandage on a human arm. Image Credit: Jian-Cheng Lai, Bao Research Group @ Stanford University.
Until now, solutions for treating long-lasting wounds have been scarce, but scientists at Stanford University have engineered a wireless smart bandage that demonstrates promise in accelerating tissue healing by tracking the wound-healing process and treating the wound concurrently.
The scientists report in an article published in the November 24th issue of Nature Biotechnology that their device enhances quicker closure of wounds, boosts fresh blood flow to the injured area, and improves skin recovery by considerably decreasing the formation of a scar.
The smart bandage is made up of wireless circuitry that employs impedance/temperature sensors to track the advancement of wound healing. If the wound has not healed well or an infection is identified, the sensors transmit the message to a central processing unit to apply more electrical stimulation spanning the wound bed to speed up tissue closure and decrease infection.
The scientists could track the sensor data in real-time on a smartphone without the requirement of wires.
Engineering Marvel
The electronic layer comprises a microcontroller unit (MCU), biosensors, memory, electrical stimulator, radio antenna, and other components. It is also only 100 microns in thickness—approximately the thickness of one coat of latex paint.
The entire circuitry is mounted atop a smartly designed hydrogel—a rubbery, skin-like polymer—that is incorporated to deliver healing electrical stimulation to the injured tissue as well as gather instantaneous biosensor data.
The polymer placed in the hydrogel is prudently designed to stick firmly to the wound surface when required, yet to peel away gently and smoothly without affecting the wound when warmed to a few degrees above the body's temperature (40°C/104°F).
In sealing the wound, the smart bandage protects as it heals. But it is not a passive tool. It is an active healing device that could transform the standard of care in the treatment of chronic wounds.
Yuanwen Jiang, Study Co-First Author and K.K. Lee Professor in Chemical Engineering, School of Engineering, Stanford University
Yuanwen Jiang is also a postdoctoral scholar in the lab of Zhenan Bao at Stanford.
Electrical stimulation, also called galvanotaxis, has been earlier reported to speed up the movement of keratinocytes to the wound area, minimize bacterial infections, and stop the formation of biofilms on wound surfaces. It is also known to proactively boost tissue growth and assist with tissue healing.
The team was able to take this well-researched technology and combine it with instantaneous biosensor data to deliver a unique automated treatment modality that is updated by biosensors.
The biosensing capabilities of the smart bandage monitor biophysical variations in the local setting, delivering a real-time, fast, robust, and very precise way to measure the condition of the wound. Plainly speaking, the smart bandage detects conductivity and temperature variations in the skin as the wound heals, the electrical impedance rises as wounds heal, and local temperatures drop as the inflammation diminishes.
With stimulation and sensing in one device, the smart bandage speeds healing, but it also keeps track as the wound is improving. We think it represents a new modality that will enable new biological discovery and the exploration of previously difficult-to-test hypotheses on the human healing process.
Artem Trotsyuk, Study Co-First Author and Chair of the Department of Surgery and Professor of Biomedical Engineering, University of Arizona (Tucson)
Artem Trotsyuk finished his graduate studies in the lab of Geoffrey Gurtner, MD, previously the Johnson & Johnson Distinguished Professor of Surgery (Emeritus) at the Stanford School of Medicine.
Welcome Results, New Directions
The team expanded their study further, attempting to comprehend why and how electrical stimulation repairs the wound faster. At present, the team is certain that electrical stimulation boosts the stimulation of pro-regenerative genes, for example, Selenop, an anti-inflammatory gene that has been known to help with pathogen clearance and wound healing, and Apoe, which has been proven to boost muscle and soft tissue formation.
Similarly, electrical stimulation raised the quantity of white blood cell populations, namely macrophages and monocytes, through the employment of greater quantities of M2 anti-inflammatory macrophages, which have been formerly reported as pro-regenerative and having a core role to play in the extracellular matrix formation that is necessary during the proliferative phases of wound repair.
The team cautions that the smart bandage is still a proof of concept, although a favorable one. However, there are still many challenges. These include expanding the device’s size to human scale, decreasing cost, and solving prolonged data storage problems—all essential to scale up to mass production should the need and opportunity come up.
Furthermore, there are possibly new sensors not presently incorporated that might be added, such as those that measure biomarkers, metabolites, and pH. There are a few probable roadblocks to clinical application, such as hydrogel rejection, wherein the skin may react to the device and develop a bad gel-to-skin combination, or biofouling of the sensors, which can result in irritation.
Regardless of these obstacles, scientists are carrying on their work and remain hopeful about the prospect of their smart bandage providing hope for patients dealing with chronic wounds.
Stanford co-first authors: Yuanwen Jiang is a postdoctoral fellow in the Bao Group; Artem Trotsyuk is a former graduate student in the Gurtner Lab; Simiao Niu is a former postdoctoral scholar in the Bao Group.
Other Stanford co-authors: Dominic Henn, Kellen Chen, Zeshaan Maan, Melanie Rodrigues, Clark A. Bonham, Michael Januszyk, Ethan Beard, Tanish Jain, Jagannath Padmanabhan, Katharina Fischer and Sun Hyung Kwon are members of the Gurtner Lab; Alana Mermin-Bunnell, Smiti Mittal, Sydney Steele, Gurupranav Gurusankar, Christopher Neimeth, Hudson Kussie, Madelyn Larson, and Serena Jing are undergraduates in the Gurtner Lab; Dharshan Sivaraj and Melissa Leeolou are MD students in the Gurtner Lab; David Perrault and Arhana Chattopadhyay are residents in plastic surgery and are members of the Gurtner Lab; Chien-Chung Shih, Jian-Cheng Lai, Jing Tang and Donglai Zhong are postdoctoral fellows; Willian Viana and Eric Zhao are graduate students; Ronjon Nag is a Stanford Distinguished Careers Institute Fellow and an Adjunct Professor of Genetics; Michael Snyder is professor and Chair of the Genetics Department; Aref Saberi, Kefan Sun, and Kui Liang; Zhenan Bao is also a member of Stanford Bio-X, the Stanford Cardiovascular Institute, the Maternal & Child Health Research Institute (MCHRI), the Precourt Institute for Energy, Sarafan ChEM-H, Stanford Woods Institute for the Environment, the Wu Tsai Human Performance Alliance, the Wu Tsai Neurosciences Institute, and an investigator of CZ Biohub; Geoffrey Gurtner is also a member of Stanford Bio-X, the Stanford Cardiovascular Institute, the Stanford Cancer Institute, and the Wu Tsai Neurosciences Institute and was the founding director of the Stanford Advanced Wound Care Center (AWCC). Kailiang Zhang is a Research Scientist with BOE Technology Group.
Journal Reference:
Jiang, Y., et al. (2022) Wireless, closed-loop, smart bandage with integrated sensors and stimulators for advanced wound care and accelerated healing. Nature Biotechnology. doi.org/10.1038/s41587-022-01528-3.