Self-Activated Electrical Stimulation for Effective Hair Regeneration via a Wearable Omnidirectional Pulse Generator

Abstract

Hair loss, a common and distressing symptom, has been plaguing humans. Various pharmacological and nonpharmacological treatments have been widely studied to achieve the desired effect for hair regeneration. As a nonpharmacological physical approach, physiologically appropriate alternating electric field plays a key role in the field of regenerative tissue engineering. Here, a universal motion-activated and wearable electric stimulation device that can effectively promote hair regeneration via random body motions was designed. Significantly facilitated hair regeneration results were obtained from Sprague-Dawley rats and nude mice. Higher hair follicle density and longer hair shaft length were observed on Sprague-Dawley rats when the device was employed compared to conventional pharmacological treatments. The device can also improve the secretion of vascular endothelial growth factor and keratinocyte growth factor and thereby alleviate hair keratin disorder, increase the number of hair follicles, and promote hair regeneration on genetically defective nude mice. This work provides an effective hair regeneration strategy in the context of a nonpharmacological self-powered wearable electronic device.

Keywords: growth factors; hair regeneration; motion-activated device; physical approach; rats and nude mice.

Figure 1.

Design and working principle of the motion-activated electric stimulation device (m-ESD). (a) Schematic configuration of the m-ESD consisting of an OTG and interdigitated dressing electrodes. (b) Enlarged-view scheme of the key components of the OTG including the CTE layer and CGE layer. (c) Optical image of the m-ESD stretched to show two functional layers of the OTG. (d) Geometric parameters of the gold CTE and copper CGE. The red dotted line is the central axis along the length direction. (e) Working principle of the OTG by sliding reversibly along any direction; (i) to (iv) represent different stages of charge transfer. (f) Representative voltage outputs of the OTG with different geometric parameters.

Figure 2.

Voltage output performance of the omnidirectional m-ESD. (a) Voltage output of the m-ESD stretching at different directions, velocities, and distances (d is the displacement distance and R represents the electrode radius). (b) Voltage peaks with regard to different displacement distances. (c) Schematic setup of the m-ESD system for hair regeneration. (d) Optical image of a SD rat wearing the m-ESD. (e) Voltage output recorded from the m-ESD on an active rat (awakened) and driven by a commercial shaker, respectively. (f) Stability and durability tests of the m-ESD.

Figure 3.

Hair regeneration effect of SD rats under the stimulation of the m-ESD. (a) Schematic illustration of HFs in skin. (b) Histomorphology schematic of the hair cycle including anagen, catagen, and telogen stages. (c) Schematic diagram of a series of interdigitated electrodes (1–4) with different gap widths. (d) Optical images of the rat with removed hair (day 0, left) and after 2-week treatment (right). (e) EF-stimulated hair shaft length as a function of the EF intensity (n = 6). (f) Top and side views of EF distribution (gap width is 1 mm) simulated by ±150 mV. (g) EF strength at different distances perpendicular to the plane of the interdigitated electrode (gap = 1 mm). All data in (e) are presented as mean ± s.d.

Figure 4.

Hair regeneration effect of SD rats under different treatment methods. (a) Comparison of hair regeneration under the influence of m-ESD, Minoxidil (MNX), vitamin D₃ (VD₃), and normal saline (NS); top: as-shaved rat; bottom: after 3-week treatment. (b) H&E staining of the epidermis under different treatment methods and time (scale bar = 200 μm). (c) Heat map of the hair shaft length from the four different treatment methods (m-ESD, MNX, VD₃, and NS) as a function of time. (d) Final hair shaft length of rats in the four experimental groups (n = 6). (e) HF proliferation of different groups over time (n = 3 for each group). The inset shows the HF proliferation percentage at the third week. (f) Hair proliferation percentage as a functional of treatment time (red dots) in comparison to the reported results by electric stimulation with different treatment parameters and MNX. All data in (e) are presented as mean ± s.d. In (d) and the inset of (e) (box plots), dots are the mean, center lines are the median, box limits are the lower quartile (Q1) and upper quartile (Q3), and whiskers are the most extreme data points that are no more than 1.5 × (Q3 – Q1) from the box limits. Statistical analysis was performed by two-tailed unpaired Student’s t tests; n.s., nonsignificant (P > 0.05); *P < 0.05, **P < 0.01, ***P < 0.001.

Figure 5.

Hair regeneration effect of nude mice under stimulation of m-ESDs. (a) Optical images of nude mice at different treatment times. (b) H&E staining of longitudinal slices of the epidermis under different stimulation time (scale bar = 200 μm). (c) Heat map of the hair shaft length as a function of time under the treatment regions of m-ESD, MNX, VD₃, and NS. (d) Final hair shaft length of nude mice in different treatment groups (n = 6). (e) HF proliferation percentage of different treatment groups as a function of time (n = 3). Inset shows the HF proliferation percentage at the 18th day. All data in (e) are presented as mean ± s.d. In (d) and the inset of (e) (box plots), dots are the mean, center lines are the median, box limits are the lower quartile (Q1) and upper quartile (Q3), and whiskers are the most extreme data points that are no more than 1.5 × (Q3 – Q1) from the box limits. Statistical analysis was performed by two-tailed unpaired Student’s t tests; n.s., nonsignificant (P > 0.05); *P < 0.05, **P < 0.01, ***P < 0.001.

Figure 6.

Growth factor expression in skin of nude mice under stimulation of m-ESDs. (a) Confocal imaging of the KGF expression as a function of time for different treatments. (b) Fluorescence intensity of KGF quantitative expression (n = 3). (c) Confocal imaging of the VEGF expression as a function of time for different treatments. (d) Fluorescence intensity of VEGF quantitative expression (n = 3). All data in (b) and (d) are presented as mean ± s.d.