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

项目摘要 伤口愈合受损对患者来说既是经济负担，也是医疗负担。在口腔中，早期和完整 伤口闭合是从拔除到移植的外科治疗成功的关键决定因素。 口腔健康是由一个不同的微生物生态系统调节的，有证据表明，这个微生物群落中的生物失调 会导致伤口愈合效果不佳。伤口愈合结果可能受到多种因素的影响 因素之一可能是电子烟，也被称为电子尼古丁传递系统(END)。 这些设备通过加热丙二醇、甘油、尼古丁、添加剂和调味品来提供气雾剂混合物。 尽管人们表达了对这些设备的担忧，但使用量仍在继续增加，部分原因是 被作为传统香烟更安全的替代品和戒烟辅助手段推向市场。然而，有证据表明 有迹象表明，末端对伤口愈合结果有负面影响。这些结果结合了一个 使用量的增加强调，迫切需要调查END的生物效应。我们的 初步数据显示，接触END会增加口腔微生物群的毒力潜力，并 在终端用户中引起活跃的促炎反应。因此，我们假设最终会促进 口腔中厌氧细菌的生长，延长了术后炎症并导致延迟 口腔伤口愈合和伤口闭合时间。我们建议通过将一个集成的 采用临床研究设计的“组学”方法，并用重述口腔创伤的体外模型进行验证 治愈事件。这种方法将测量末端使用对口腔伤口愈合的临床效果，以及 找出这些临床事件背后的机制。在目标1中，我们将量化END对临床的影响 口腔创伤愈合的纵向病例对照干预研究。活检样本将用于宿主 将测量转录组、转录组和代谢组学以及伤口闭合时间。在AIM 2，我们将使用皮肤创伤愈合的体外模型来验证这些结果，并探讨其机制。 通过这些末端影响伤口愈合事件。因为成功的伤口愈合依赖于口腔微生物 动态平衡，我们将结合宿主上皮与其下的成纤维细胞层和构建核心微生物。 寄主转录组、转录组和代谢组学将通过RT-qPCR进行分析和验证。通过 将临床模型的复杂性与高度受控的体外实验相结合，拟议的研究将 为理解END在破坏宿主微生物动态平衡中的作用提供重要证据 重新认识末端对口腔创面愈合影响的复杂性并建立末端指标 相关寄主微生物生态失调。

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.