Effective Wound Healing Enabled by Discrete Alternative Electric Fields from Wearable Nanogenerators

Abstract

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.

Keywords: nanogenerator; physical therapy; self-powering; wearable device; wound healing.

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-β, 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).