Perturbation of Craniofacial Morphogenesis, Healing, and Regeneration by E-cigarette Aerosol Mixtures

 描述（由申请人提供）：全世界有超过13亿人使用烟草产品。在大多数发达国家，烟草产品受到严格管制，在这些管制下，使用量有所减少。然而，由于发展中国家的消费增加，全球烟草消费正在增加。电子烟是电池供电的尼古丁输送系统，被宣传为比香烟“更健康”，在全球越来越受欢迎。到2014年， 超过466个品牌存在超过7764独特风味的尼古丁溶液（电子液体）。虽然一些国家对电子烟的销售实施了限制，但这些设备大多不受监管。虽然人们认识到吸烟对口面部区域的有害影响，但对雾化电子液体的影响知之甚少。本申请的目标是使用多系统方法，通过强大的体外和体内模型来确定最敏感的细胞类型和组织， 这些气溶胶混合物对颅面结构的发育、愈合和再生的影响。利用口腔颌面部组织的细胞作为体外模型，我们将进行生物学、生物化学和分子询问，以表征细胞毒性、增殖性、 气溶胶混合物的细胞凋亡和炎症效应。此外，我们将使用我们新的非洲爪蟾模型来阐明电子烟气溶胶对颅面发育的影响。这些发育研究将通过我们的慢性暴露模型进行补充，在该模型中，小鼠将在怀孕期间暴露于电子烟气溶胶，并研究其后代的口面发育。我们的综合方法还将研究电子烟气溶胶在我们的伤口愈合和再生模型中的作用，包括常见的颅面外科手术，如拔牙和牙科植入物，以及最近的方法，如骨组织工程。这种方法将导致详细了解电子烟气溶胶混合物对颅面组织的体内平衡、发育、伤口愈合和再生的影响。

 DESCRIPTION (provided by applicant): More than 1.3 billion people worldwide use tobacco products. Tobacco products are tightly regulated in most developed countries, and with these regulations, use has decreased. However, tobacco consumption is increasing globally due to increased consumption in developing nations. E-cigarettes are battery-powered nicotine delivery systems advertised as "healthier" than cigarettes that are gaining in popularity globally. By 2014, more than 466 brands existed with more than 7764 uniquely flavored nicotine solutions (e-liquids). While some countries have imposed restrictions sales of e-cigarettes, these devices are mostly unregulated. While the harmful effects of cigarette smoking in the orofacial region are recognized, little is known about the effects of aerosolized e-liquids. The goal of this applicatio is to unravel the effects of e-cigarette aerosol mixtures using a multi-system approach with robust in vitro and in vivo models to identify the most susceptible cell types and tissues, as well as the effects of these aerosol mixtures in the development, healing, and regeneration of craniofacial structures. Using cells from orofacial tissues as in vitro model, we will conduct biological, biochemical, and molecular interrogations to characterize the cytotoxic, proliferative, apoptotic, and inflammatory effects of aerosol mixtures. Additionally, we will use our novel Xenopus laevis model to elucidate the effects of e-cigarette aerosols in craniofacial development. These development studies will be complemented by our chronic exposure model, in which mice will be exposed to e-cigarette aerosols during pregnancy and the effects on their offspring's orofacial development studied. Our comprehensive approach will also investigate the effects of e-cigarette aerosols in our models of wound healing and regeneration, including common craniofacial surgical procedures like tooth extractions and dental implants, as well as more recent methods like bone tissue engineering. This approach will result in a detailed understanding of the effects of e- cigarette aerosol mixtures on the homeostasis, development, wound healing, and regeneration of craniofacial tissues.