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Principal Investigator: Haluk Beyenal
Organization: MAYO CLINIC ROCHESTER
Fiscal Year: 2024
Award: $424,176
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY
Biofilm bacteria cause two-thirds of infections in modern clinical practice, including wound and device-
related infections. Host defenses and most available antibiotics are inactive against biofilms, rendering the
infections they cause challenging to treat. Given the failure of antibiotics in management of biofilm-associated
infections, novel and innovative approaches are needed. Avoiding antibiotics will also decrease the dysbiosis
and selection of genotypic antibiotic resistance linked to their use. We are developing electrical anti-biofilm
strategies. In the original funding period, we developed the “electricidal effect,” which uses fixed direct current
(DC). Though fixed DC exhibited activity in vitro and in animal models of orthopedic foreign body infection,
concerns about mechanistic non-specificity, and challenges in clinical delivery for orthopedic infections (at least
as an initial application), led us to propose a new approach. Here, we propose a mechanistically-precise
electrochemical strategy (distinct from fixed DC), that will specifically deliver one or the other (or both) of two
anti-biofilm chemicals – hydrogen peroxide (H2O2) and/or hypochlorous acid (HOCl). We have also moved to a
more clinically feasible target – wound infections. Our new approach employs a completely novel, tunable –
potential-controlled – electrochemical system, which will cleanly deliver continuous low concentrations of H2O2
and/or HOCl, suitable for biofilm killing, without compromising wound healing. Importantly, both chemicals have
applications in wound care, but use has been hindered by rapid decomposition of their raw chemical forms. To
bring together the biology, microbiology, electrochemistry, engineering and animal model expertise required for
our studies, we are newly collaborating with an electrochemist and biofilm engineer, Haluk Beyenal, PhD. In
collaboration, we will develop scalable electrochemical bandages (e-bandages) composed of carbon fibers that
will generate sustained, controlled quantities of H2O2 and/or HOCl in the presence of specific applied potential,
providing an easy-to-use, antibiotic-free approach for treatment of infected wounds and promotion of wound
healing. The technology being applied was not available in the prior funding period. We have built prototype
devices that generate continuous, controlled concentrations of H2O2 or HOCl (based on applied potential) in
amounts that reduce biofilms. Both H2O2- and HOCl-generating prototypes reduced Acinetobacter baumannii,
Pseudomonas aeruginosa, and Staphylococcus aureus biofilms in vitro. Further, the HOCl-generating
prototype reduced the number of live bacterial cells of all three species on porcine dermal explants, and the
H2O2-generating prototype did the same against A. baumannii on explants, without damaging the animal
tissue. In Aim 1, we will build e-bandages and confirm, using in vitro studies, their biofilm treatment properties,
tuning them to ensure lack of toxicity. In Aim 2, we will demonstrate activity and safety of the e-bandages in a
murine wound infection model. Our goal is to have a product ready for human testing at the end of our studies.
Terms: <A baumanni><A baumannii><A. baumanni><A. baumannii><A.baumannii><Acinetobacter baumanni><Acinetobacter baumannii><Acne><Address><Animal Model><Animal Models and Related Studies><Animal Testing><Animals><Antibiotic Agents><Antibiotic Drugs><Antibiotic Resistance><Antibiotics><Bacteria><Bacterial Infections><Bandage><Biocide><Biology><Body Tissues><Cell Body><Cells><Chemicals><Clinical><Collaborations><Dermal><Development><Devices><Doctor of Philosophy><Electrochemistry><Electrodes><Engineering><Ensure><Exhibits><Failure><Family suidae><Fibroblasts><Foreign Bodies><Funding><Genotype><Genus staphylococcus><Goals><Grant><H2O2><Host Defense><Human><Hydrogen Peroxide><Hydroperoxide><Hypochlorous Acid><In Vitro><Individual><Infection><Laboratories><Link><Medical><Medicine><Methods><Mice><Mice Mammals><Microbial Biofilms><Microbiology><Miscellaneous Antibiotic><Modeling><Modern Man><Modernization><Murine><Mus><O element><O2 element><Orthopedic><Orthopedic Surgical Profession><Orthopedics><Oxygen><P aeruginosa><P. aeruginosa><Ph.D.><PhD><Pigs><Property><Pseudomonas aeruginosa><Pseudomonas pyocyanea><Refractory><Resistance><Resistance to antibiotics><Resistant to antibiotics><S aureus><S. aureus><Safety><Staph aureus><Staphylococcus><Staphylococcus aureus><Suidae><Swine><System><Technology><Testing><Textiles><Tissues><Toxic effect><Toxicities><Wound Infection><Wound Repair><Yeasts><animal tissue><anti-microbial><anti-microbial agent><anti-microbial drug><antibiotic drug resistance><antibiotic resistant><antimicrobial><bacteria infection><bacterial disease><biofilm><carbon felt><carbon fiber><clinic ready><clinical practice><clinical ready><design><design and construct><design and construction><designing><developmental><dysbacteriosis><dysbiosis><dysbiotic><experiment><experimental research><experimental study><experiments><fabric><flexibility><flexible><in vitro activity><in vivo><infected wound><innovate><innovation><innovative><keratinocyte differentiation><microbial imbalance><microorganism><migration><model of animal><new approaches><new drug treatments><new drugs><new pharmacological therapeutic><new therapeutics><new therapy><next generation therapeutics><novel><novel approaches><novel drug treatments><novel drugs><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel strategies><novel strategy><novel therapeutics><novel therapy><porcine><prevent><preventing><prototype><resistant><success><suid><tissue wound><treat wound><voltage><wound><wound assessment><wound care><wound healing><wound management><wound monitoring><wound recovery><wound resolution><wound therapeutics><wound therapy><wound treatment><wounding><wounds>