Investigation of cold plasma for healing alcohol-induced tissue injury

Abstract:
Binge drinking of alcohol beverages hinders tissue repair and amplifies the susceptibility to infection. The
prevalence as well as the risks associated with binge drinking poses a significant concern in the United States.
Binge drinking impairs the three key phases of wound healing: inflammation, proliferation, and remodeling.
Specifically, during the inflammation phase, binge drinking diminishes the function of pro-inflammatory cytokines,
neutrophils, and macrophages, thus compromising the innate immune system's ability to combat pathogens. The
efficacy of current wound healing methods is constrained by the vulnerability to wound infection which is
exacerbated by concurrent binge drinking. Cold Plasma (CP) has recently gained substantial attention in clinical
practice due to its regenerative properties and its ability to prevent infection. Previous studies have shown that
CP treatment is involved in the wound healing mediated by the Nrf2 pathway and Wnt/β‑catenin signaling
pathway.
Taken these solid premises together, we hypothesize that CP will improve impaired wound healing and
mitigate the increased vulnerability to infection caused by binge drinking. To substantiate these hypotheses, we
have proposed two following specific aims using F344 rat model and human skin organoid model, respectively.
Aim 1 is to characterize wound healing properties of CP in F344 rats following binge exposure to alcohol.
This aim is to examine wound closure properties of CP and to reveal molecular mechanisms underlying CP
modulation of wound healing in binge EtOH intoxicated F344 rats. Aim 2 is to generate an in-vitro wound
healing model using hiPSC derived skin organoids and to investigate the potential wound healing
properties of CP in these skin organoids given binge level of EtOH. This aim represents the translational
aspect of our studies. We first will develop and characterize 3D skin organoids using human induced pluripotent
stem cells (hiPSC) and then identify the potential wound healing properties of CP in alcohol-treated human skin
organoids. In addition, we will study molecular mechanisms and signal pathways underlying CP modulation of
wound healing in alcohol treated skin organoids using both immunofluorescence and gene expression analysis.
These studies are highly significant because 1) we are to demonstrate the medical use of CP in wound healing
associated with EtOH intoxication, and 2) we are to address the translational value of the proposed studies using
F344 rat model and human culture of skin organoids. Successful completion of this small R03 grant award will
provide valuable therapeutic clues in CP modulation of the wound healing during EtOH intoxication. The study
outcomes shall shift the paradigms regarding the interplay between wound healing properties of CP and alcohol-
induced impairment of wound healing, eventually leading to clinical application of CP in wound healing during
EtOH intoxication. We expect a full R01 project to be developed in conclusion of this small R03 project.

Grant Number: 5R03AA031535-02
NIH Institute/Center: NIH
Principal Investigator: Sulie Chang