E-cigarettes and oral wound healing: an integrated omics approach

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Project Abstract Impaired wound healing is both a financial and medical burden for patients. In the oral cavity, early and complete wound closure is a critical determinant of the success of surgical treatments ranging from extractions to grafting. Oral health is mediated by a diverse microbial ecosystem, and there is evidence that dysbiosis in this microbiome can contribute to poor wound healing outcomes. Wound healing outcomes can be influenced by a wide range of factors, one of which might be e-cigarettes, also referred to as electronic nicotine delivery systems (ENDS). These devices deliver an aerosol mixture by heating propylene glycol, glycerol, nicotine, additives and flavorings. Although concerns have been voiced about these devices, usage continues to increase, partially as a result of being marketed as a safer alternative to traditional cigarettes and as a smoking cessation aid. However, evidence is emerging to suggest that ENDS negatively impact wound healing outcomes. These results combined with an increase in usage emphasize that there is an urgent need to investigate the biological effects of ENDS. Our preliminary data has shown that ENDS exposure increases the virulence potential of the oral microbiome and elicits a brisk proinflammatory response in ENDS users. Therefore, we hypothesize that ENDS promote the growth of anaerobic bacteria in the oral cavity, prolonging post-surgical inflammation and resulting in delayed oral wound healing and time to wound closure. We propose to test this hypothesis by combining an integrated ‘omics’ approach with a clinical study design and validate this with an in vitro model that recapitulates oral wound healing events. This approach will measure the clinical effects of ENDS use on oral wound healing, as well as identify the mechanisms behind these clinical events. In Aim 1, we will quantify the clinical impacts of ENDS on oral wound healing using a longitudinal case-control intervention study. Biopsy samples will be utilized for host transcriptomics, metatranscriptomics and metabolomics and the time to wound closure will be measured. In Aim 2, we will validate these results using an in vitro model of cutaneous wound healing and explore the mechanisms by which ENDS impact wound healing events. Since successful wound healing relies on oral microbial homeostasis, we will combine host epithelium with an underlying fibroblast layer and construct of core microbes. Host transcriptomics, metatranscriptomics and metabolomics will be analyzed and validated with RT-qPCR. By combining the complexity of a clinical model with a highly controlled in vitro experiment, the proposed study will provide important evidence to understand the role of ENDS in disrupting host microbial homeostasis, provide new understanding of the complexities of ENDS on oral wound healing and establish indicators of ENDS associated host microbial dysbiosis.