S. Roy1, A. Das1, S. Mathew1, P. D. Ghatak1, S. Khanna1, S. Prakash2, V. Subramaniam2, D. J. Wozniak3, C. K. Sen1 1The Ohio State University Wexner Medical Center,Comprehensive Wound Center, Center For Regenerative Medicine And Cell Based Therapies, Department Of Surgery, Davis Heart And Lung Research Institute,Columbus, OHIO, USA 2The Ohio State University,Department Of Mechanical And Aerospace Engineering,Columbus, OHIO, USA 3The Ohio State University,Department Of Microbial Infection And Immunity, Department Of Microbiology, Center For Microbial Interface Biology,Columbus, OHIO, USA
Introduction: Infection is a significant threat in the effective management of acute and chronic wounds. Adding further to the complexity is the occurrence of multidrug-resistant organisms and/or virulent pathogens as biofilm infection resulting in persistent infections. Interestingly, bacteria produce positively charged polysaccharides as a component of the overall extracellular polymeric substance, the hallmark of the biofilm matrix. Thus, electrostatic forces represent a natural contributor enabling the attachment and encasement of bacteria during biofilm development and maturation. The current work employs a therapeutic flow of electric charge (EDT) to disrupt bioelectric forces with the goal of biofilm disassembly. Because EDT is not subject to the metabolic pathways of drug resistance, it has the potential to circumvent drug resistance and disrupt biofilms. The primary objective of this study was to determine the ability of optimized electroceutical EDT dressings to eliminate mixed species biofilm infection in a preclinical porcine burn infection model.
Methods: Our first generation technology (EDTlo) is a commercialized (Procellera®) and FDA cleared as wound care dressing. This dressing, composed of silver and zinc redox couple printed on a polyester textile is wireless and does not need any external power supply making it well suited for application as disposable wound care dressing. We have developed a prototype next-generation EDT (EDThi) with inherent scalability of electric field for dosing purposes and performed in vitro and preclinical in vivo studies. EDThi is an interdigitated pattern printed (medical grade silver) dressing powered by a 6V DC battery. The design includes a safety fuse to prevent accidental damage along with a switch to manually control the ON/OFF capability. We have developed and reported first persistent infection long-term wound biofilm infection in porcine (preclinical) model. The safety and efficacy of EDT was tested in porcine mixed species biofilm infection model.
Results: CFU, SEM and CLSM studies clearly demonstrated a significant attenuation of bacteria growth (p<0.05, n=4) as well as biofilm integrity and persistence (p<0.05, n=4) following EDT treatments. The safety of EDT on host wound healing was determined using histopathology and wound re-epithelialization assessment. No host cell necrosis or growth inhibition was noted in EDT treated groups, a marked increase in wound re-epithelialization (p<0.05, n=4) was observed in EDT treated group indicating the intervention is safe for host. EDT treatment significantly protected against biofilm induced skin barrier function disruption via a miR-9-E-cadherin pathway.
Conclusion: The current pre-clinical work provided evidence that therapeutic flow of electric charge in form of EDT dressings may be effectively used as an alternative to pharmacological intervention to combat biofilm infection in wounds.