Imaging the electric field associated with mouse and human skin wounds

Abstract

We have developed a noninvasive instrument called the bioelectric field imager (BFI) for mapping the electric field between the epidermis and the stratum corneum near wounds in both mouse and human skin. Rather than touching the skin, the BFI vibrates a small metal probe with a displacement of 180 μm in air above the skin to detect the surface potential of the epidermis through capacitative coupling. Here we describe our first application of the BFI measuring the electric field between the stratum corneum and epidermis at the margin of skin wounds in mice. We measured an electric field of 177 ± 14 (61) mV/mm immediately upon wounding and the field lines pointed away from the wound in all directions around it. Because the wound current flows immediately upon wounding, this is the first signal indicating skin damage. This electric field is generated at the outer surface of the epidermis by the outward flow of the current of injury. An equal and opposite current must flow within the multilayered epidermis to generate an intraepidermal field with the negative pole at the wound site. Because the current flowing within the multilayered epidermis is spread over a larger area, the current density and subsequent E field generated in that region is expected to be smaller than that measured by the BFI beneath the stratum corneum. The field beneath the stratum corneum typically remained in the 150-200 mV/ mm range for 3 days and then began to decline over the next few days, falling to zero once wound healing was complete. The mean wound field strength decreased by 64 ± 7% following the application of the sodium channel blocker, amiloride, to the skin near the wound and increased by 82 ± 21% following the application of the Cl -channel activator, prostaglandin E2.Electrical signals play an integral role in the function of many of our organ systems and are routinely used in the diagnosis of disease in the heart and nervous system. Our largest organ, the skin, generates a voltage across itself everywhere on the body, yet the signaling function of this "skin battery" remains largely unexplored.This skin battery will drive an ionic current out through any wound where the resistance is low and as this "wound current" flows out of the wound it will in turn generate an electric field within the skin along the lines of current flow. Dubois-Reymond first discovered that ionic currents exit skin wounds 165 years ago using a galvanometer. 1 This was confirmed by Illingworth and Barker 2 using the more modern vibrating probe technique. 3,4 They measured up to 10 μA/cm 2 exiting accidentally amputated fingertips in children during a 2-week period following the injury. This wound current flows through the tissue which has a certain resistivity so this flow must generate an electric field in the skin bordering the has not yet been measured in humans, it has been measured in the skin of guinea pigs, newts, and salamanders (reviewed in 5 ). The lack of human studies is due, in part, to the difficulty of carrying out recordings in hum...

Dynamics of intracellular calcium in cultured human keratinocytes after localized cell damage

“…Therefore, spatio-temporal information defining the damaged site would be needed to regulate wound healing. It has been shown that an endogenous electric field is formed around the wound during the wound-healing process, and the electric field induces keratinocyte migration for re-epithelialization (12). Recent work showed that a direct current electric field induced [Ca 2+ ] i elevation at the edges of aggregates of keratinocytes (13).…”

Harnessing the Electric Spark of Life to Cure Skin Wounds

“…More recent work has confirmed the existence and intensity of these endogenously generated electric currents in mouse and human skin wounds. 10,11,13 These epidermal electrical currents activate several major signaling cascades and promote the directional migration of many cell types involved in wound healing.…”

“…These endogenously generated EFs contribute to the guidance of cells, blood vessels, and nerves toward the wound site. Based on Nuccitelli et al 13 and Shaw and Martin. 15 To see this illustration in color, the reader is referred to the web version of this article at www.…”

“…The hypothesis that wound repair is guided by electric signals is supported by three main lines of evidence: (1) Strong electric currents exist at wounds and are required for effective wound healing; [9][10][11][12][13] (2) inhibition of endogenous currents specifically impairs wound closure; 13,14 and (3) applying an exogenous electric current of physiological intensity can induce faster wound closure both in vitro and in vivo. [3][4][5][6][7][8]14 In this review, we have compiled the present knowledge on the effects that electric fields (EFs) have on the behavior of cells involved in the healing response, and we focus on the mechanistic understanding of how electric signals are sensed and transmitted within these cells to influence their physiological behavior.…”

In vitro electrical-stimulated wound-healing chip for studying electric field-assisted wound-healing process

“…This device has been applied to image the distribution of EF around skin wounds in both mice and humans. 44 Its basic principle is applying different voltages to a vibrational probe and then measuring the capacitance between the probe and the unknown surface. Once the capacitance is zero, the voltage of the unknown is determined to be equal to that of the probe.…”