Fig 1.
Macrophage phenotype, wound schematic, and endogenous electric field at mouse wound.
(A). A battery-powered bioelectronic device for EF delivery was applied to the mouse wound. (B) the EF delivery device generates EFs in the wound through the hydrogels and electrode, pointing from wound edge to center. Macrophages and new epithelial cells would be modulated in the healing process.
Fig 2.
In vivo bioelectronic device that delivers tuned electric field for wound treatment.
(A) In this setup, the external power source generates a potential difference between the reservoir embedded Ag/AgCl electrodes. This potential difference drives the flow of electric current through the electrolyte, Steinberg solution, filling the reservoirs. The electrolyte, being a conductive solution, facilitates the movement of ions between the hydrogel-filled capillaries. The hydrogel-filled capillaries function similarly to the salt bridge utilized in the in vitro experiment. The hydrogel-filled capillaries serve as a conducive interface, establishing direct contact between the device and the wound bed for efficient bioelectronic transmission of the electric field. The Ag reference electrode serves as a reference point for the electric potential. The potential difference creates an electric gradient that extends from the active hydrogel-filled capillaries electrodes towards the reference electrode, generating the desired lateral electric field that establishes a 125 ± 75 mV/mm EF in the wound pointing from edge to and converging at the wound center. (Right Panel of A) Exploded view detailing the components that make up the modules of the bioelectronic device. (B) Schematic of the circuit. (C) Actuation of electric field treatment. LED on indicates treatment is actuating. After 250-minutes the treatment stops and goes on sleep mode. (D) Schematic diagram of the electric circuitry on a wound. (E) Bottom view of device and how it generates the electric field.
Fig 3.
Electrical stimulation decreased M1/M2 ratio mainly through reducing M1 marker-positive macrophages during wound healing in vivo.
(A) Representative immunofluorescence images of dorsal skin wound tissues from mice 3 days after wounding with/without EF treatment. Seven μm thick tissue sections were co-stained with F4/80 (showing in green in merged images), iNOS (magenta), and CD206 (red) as indicated. Nuclei were labeled with DAPI (blue). n = 13 mice for the control, and n = 9 for the EF treated group. 5 images were taken and quantified for each wound. (B) Image of histomorphometric analysis of wound re-epithelization. Representative wounds: Green line indicates area of wound re-epithelialization in control and EF treated wounds. (C) M1 to M2 ratios from experiments shown in A and B. Plot shows mean ± standard error. (D) Quantitation of percent re-epithelialization. P values and percentage of changes from the control (CTRL) are as indicated. Plot shows mean ± standard error.