Weibo CAI, et al.


E-bandage generates electricity, speeds wound healing in rats
Skin has a remarkable ability to heal itself. But in some cases, wounds heal very slowly or not at all, putting a person at risk for chronic pain, infection and scarring. Now, researchers have developed a self-powered bandage that generates an electric field over an injury, dramatically reducing the healing time for skin wounds in rats. They report their results in ACS Nano.

Chronic skin wounds include diabetic foot ulcers, venous ulcers and non-healing surgical wounds. Doctors have tried various approaches to help chronic wounds heal, including bandaging, dressing, exposure to oxygen and growth-factor therapy, but they often show limited effectiveness. As early as the 1960s, researchers observed that electrical stimulation could help skin wounds heal. However, the equipment for generating the electric field is often large and may require patient hospitalization. Weibo Cai, Xudong Wang and colleagues wanted to develop a flexible, self-powered bandage that could convert skin movements into a therapeutic electric field.

To power their electric bandage, or e-bandage, the researchers made a wearable nanogenerator by overlapping sheets of polytetrafluoroethylene (PTFE), copper foil and polyethylene terephthalate (PET). The nanogenerator converted skin movements, which occur during normal activity or even breathing, into small electrical pulses. This current flowed to two working electrodes that were placed on either side of the skin wound to produce a weak electric field. The team tested the device by placing it over wounds on rats' backs. Wounds covered by e-bandages closed within 3 days, compared with 12 days for a control bandage with no electric field. The researchers attribute the faster wound healing to enhanced fibroblast migration, proliferation and differentiation induced by the electric field. 

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Effective Wound Healing Enabled by Discrete Alternative Electric Fields from Wearable Nanogenerators.
E-bandage generates electricity, speeds wound healing in rats
Yin Long, et al.

Skin wound healing is a major health care issue. While electric stimulations have been known for decades to be effective for facilitating skin wound recovery, practical applications are still largely limited by the clumsy electrical systems. Here, we report an efficient electrical bandage for accelerated skin wound healing. On the bandage, an alternating discrete electric field is generated by a wearable nanogenerator by converting mechanical displacement from skin movements into electricity. Rat studies demonstrated rapid closure of a full-thickness rectangular skin wound within 3 days as compared to 12 days of usual contraction-based healing processes in rodents. From in vitro studies, the accelerated skin wound healing was attributed to electric field-facilitated fibroblast migration, proliferation, and transdifferentiation. This self-powered electric-dressing modality could lead to a facile therapeutic strategy for nonhealing skin wound treatment...

The therapeutic effects of ES for wound healing were first observed in the late 20th century.(17,18) It is believed that an electric field is essential for directing many cellular processes that lead to orderly healing naturally.(19,20) As summarized in the literature,(21) ES can decrease edema around the electrode; lyse or liquify necrotic tissue; stimulate growth of granulation tissue; increase blood flow; cause fibroblasts to proliferate and make collagen; induce epidermal cell migration; attract neutrophils; stimulate neurite growth directionally; promote epithelial growth and organization; decrease mast cells in healing wounds; attract macrophages; and stimulate receptor sites to accept certain growth factors. Although the influence from an electric field can be significant, clinical applications of electrical stimulation for wound healing typically involves large-sized extracorporeal devices to provide appropriate electrical fields and may require patient hospitalization.

The recent innovation of nanogenerator (NG) technology opened a route for generating periodic biphasic electric pulses by locally converting mechanical displacements, such as body or muscle motions.(22-27) This exceptional capability makes NG a candidate for producing electrical stimulations that is self-sustainable and biologically responsive.

Figure 1. NG-based bandage and potential wound-healing application. (a) Schematic image of NG configuration. The digital image of NG is shown below. (b) Bending modulus of PET, PET–Cu foil, and PET–Cu foil–PTFE. (c) Cell viability of cells on PTFE, PET, and blank control. (d) Biomechanical energy harvesting of NG. The chest of SD rat was wrapped by the bandage which harvested the biomechanical energy from rat breathing. (e) Electrical output of NG driven by the breathing of rat with different frequencies. (f) Digital images of the experimental setup for NG-driven linear incisional wound healing. (g) Wound-healing mechanism under endogenous electric field.

Figure 2. Wound healing under the stimulation of activated/inactivated electric field (EF). (a) Digital image of experimental group (with electrode connected to NG) and control group (no connection between electrode and NG) attached on the wound of rat. (b) Front and (c) lateral view of electric field distribution (simulated by COMSOL). (d) Digital image of wound recovery after 2 days in both experimental (dashed red rectangle) and control (dashed blue rectangle) groups. (e, f) Enlarged images of the wound areas from (d).

Figure 3. Scaled wound healing and healing efficiency comparison. (a) Digital image of a 3-day healing process for rectangular wounds with (experimental group) and without (control group) electric field. (b) Representative example of H&E stained sections of the center of a wound after 2 days of treatment with or without NG. Scale bar is 2.5 mm. (c) Digital images of time-varying (0-72 h) healing process for square wounds with (experimental group) and without (control group) electrical field. Scale bar is 5 mm. (d) Wound area as a function of time with (red curve) and without (black curve) electric field stimulation (n = 3).

Figure 4. Influence of electric field on cells. (a) Schematic image of cells cultured in 96-well plate with stimulation from NG and cell viability of different columns in a 96-well plate (n = 8). (b) Schematic image of cells cultured in a dish with Au electrodes connected and disconnected to NG generated pulse voltage. Middle inset is the simulated electric filed distribution in the culture dish when the electrodes are connected to a NG with ±2 V out voltage. (c) Cultured cell morphology at different time points without (control) and with (experimental) electrical stimulation. Obvious proliferation and differentiation of cells at later time points were observed. (d) Western blot analysis and comparison of TGF-ß, EGF, and VEGF growth factors (n= 3) with and without NG stimulation. (e) ROS results of blank control (BC), AC (alternating electric field generated by function generator), and NG (n = 5, p < 0.01).

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