29 November 2022

Electroplating

A smart patch will heal the wound with electricity and peel off on command

Oleg Lischuk, N+1

American researchers have developed and preclinically tested a wireless smart patch for monitoring the condition of the wound and its electrical stimulation in order to accelerate healing. The report on the work was published in the journal Nature Biotechnology (Jiang et al., Wireless, closed-loop, smart bandage with integrated sensors and stimulators for advanced wound care and accelerated healing).

Chronic non-healing wounds that do not close within 8-12 weeks pose a serious problem for public health, as they are associated with loss of function and mobility of the affected part of the body; social stress, isolation, depression and anxiety; prolonged hospitalization; increased overall morbidity and mortality. In the United States alone, they occur in more than six million people and cost more than $25 billion a year. Normally, wound healing goes through the stages of inflammation, formation of new tissue and remodeling, in which different types of cells are involved. With deep tissue damage (for example, with burns, frostbite, wound infection) or concomitant conditions (such as diabetes mellitus and other metabolic disorders, generalized infections, ischemia, immunosuppression, radiation damage) these processes are disrupted, and wounds do not heal for a long time.

Modern methods of treating such injuries, including the use of growth factors, extracellular matrix, bioengineered skin and negative pressure, have moderate effectiveness. To improve it, various scientific groups create smart patches that help monitor the condition of the wound (acidity, temperature, oxygenation, electrical resistance, mechanical movements, enzyme activity) in real time or perform certain therapeutic effects. The functionality of most of these developments is limited, in addition, their use is associated with the risk of secondary tissue injury when the device is detached.

To combine the advantages of sensory and therapeutic smart patches in one device, Stanford University researchers led by Zhenan Bao and Geoffrey Gurtner have developed a wireless flexible bioelectronic system with controlled adhesion. As a basis, they used a 100-micrometer layer of a biocompatible conductive dense hydrogel made of poly(N-isopropylacrylamide-co-acrylamide) and poly(3,4-ethylenedioxythiophene):polystyrene sulfate (PNIPAM-ran-AAm and PEDOT:PSS), which adheres well to the skin at room temperature, but loses stickiness when heated to 40 degrees Celsius.

A miniature flexible printed circuit board (FPCB) containing an antenna for wireless power supply with a resonant frequency of 13.56 megahertz; a microcontroller; memory modules; a crystal oscillator, sensors and filters for continuous two-channel recording of temperature and electrical resistance of tissues by means of short-range contactless communication (NFC) according to the ISO 15693 protocol; a parallel circuit for programmable electrical stimulation was fixed on a hydrogel substrate. wounds in order to accelerate its healing. As previous studies have shown, currents with certain characteristics reduce bacterial colonization of wounds and the formation of biofilms, as well as improve tissue perfusion and cause galvanotaxis of keratinocytes (epidermis cells) and fibroblasts (connective tissue cells) that close the skin defect.

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Preclinical tests of the hybrid smart patch on mice have shown that it does not restrict the movement of animals, does not cause skin irritation when worn continuously for 15 days and provides stable continuous monitoring of temperature and resistance. With artificially inflicted cuts in healthy mice and with a streptozotocin model of diabetes mellitus, as well as with burns, electrical stimulation using the device provided approximately a 25 percent acceleration of healing and a 50 percent improvement in skin remodeling compared to conventional sterile dressing. In particular, the smart patch increased the thickness of the skin on the wound, the synthesis of collagen in it, the number of new microvessels, the expression of PECAM-1 (platelet and endothelial cell adhesion molecule 1, CD31) and smooth muscle alpha-actin (a marker of myofibroblasts). In addition, the device recognized the development of wound infection in the early stages and automatically modulated treatment according to the feedback principle.

Although galvanotaxis of keratinocytes and fibroblasts under the action of electrostimulation was known, its effect on immune cells, which serve as a critical regulator of all stages of wound healing, has not been practically studied. To understand this issue, the authors of the work used a model of parabiosis (surgical union of circulatory systems) of ordinary mice with wounds and trengenic mice expressing green fluorescent protein (GFP). On the fifth day of smart patch therapy, tissue samples were taken from wounds in the main group or without it in the control group and single cell RNA sequencing (scRNA-seq) was performed. The greatest number of differentially expressed genes under the action of electrostimulation was observed in monocytes and macrophages. A more detailed study of these cells revealed an increased expression of CD74, SELENOP, APOE, MRC1, CD163 and FABP5 genes involved in tissue regeneration processes.

The authors of the work note that the tests carried out on the demonstration samples of the smart patch serve only as a confirmation of the concept. For its introduction into clinical practice and mass production, it is necessary to solve a number of problems, such as scaling the size for the treatment of extensive injuries, reducing the price and ensuring long-term data storage, as well as possibly adding sensors that register pH, levels of metabolites and biomarkers, which is planned to be done at the next stages of development.

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