Wireless Electric Field Stimulation Promotes Vascularization And Diabetic Wound Healing In Porcine Model
Nava P. Rijal1, Vasuretha Chandar1, Alex Madzia1, Rebekah Deardurff1, Dmitrii Kruglov2, Andrei Kogan2, Daria A. Narmoneva1.
1University of Cincinnati, Department of Biomedical Engineering, Cincinnati, OH, USA, 2University of Cincinnati, Department of Physics, Cincinnati, OH, USA.
Diabetes is associated with impaired vasculature and altered tissue microenvironment that contribute to nonhealing diabetic ulcers. Although electric field (EF)-based therapies are promising, progress is impeded by poor understanding of the EF interactions with tissues. The goal is to develop a wireless electrotherapy for chronic wounds using a novel EF modality designed to activate vascular cells within the wound. The hypothesis is that the specific EF stimulation will enhance vascularization, reduce inflammation and improve wound healing in both acute and diabetic porcine models, vs. control (no-EF) treatment. 2x2 cm wounds (n=12-16) were created on the dorsum of STZ-diabetic and non-diabetic Yorkshire pigs, covered with Tegaderm™ and treated with wireless non-thermal EF (1hr/day, 3-5days/week, up to 4wks) or served as controls (6-8 wounds/group). EF distribution in the wound was determined using numerical in-situ simulation (ANSOFT/HFSS). Histological analyses demonstrated that EF stimulation results in a dramatic 80-100% increase in the blood vessel density vs. non-EF controls in non-diabetic (p<0.0005) and diabetic wounds (p<0.005), with EF-stimulated wounds (both diabetic and non-diabetic) achieving epidermal reestablishment similar to that of the unwounded skin, indicating regenerative healing and less scarring. There was a (non-significant) trend for higher VEGF expression in the EF group. EF treatment significantly enhanced wound reepithelization in non-diabetic (4.2cm2 vs. 3.3cm2, p<0.01, day5) and diabetic groups (2.5cm2 vs. 3.04cm2, p<0.01, day8) vs. no-EF controls, and improved repair tissue strength (5.02MPa vs. 4.04MPa, p<0.01, d15, non-diabetic group). In conclusion, the novel non-contact EF stimulation may be a promising strategy for restorative wound healing therapies to improve healing outcomes and decrease amputations in patients with non-healing ulcers.
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