Pulmonary fibrosis and COVID-19: real-time monitoring of tissue stiffness in a bioengineered model of fibrotic epithelium

目前，世界各国的努力都集中在保持社会距离、进行广泛检测、开发新药和疫苗等“使曲线变平”上，因此，如何解决康复患者的长期健康问题已成为下一个主要问题。领导COVID-19长期后果临床研究项目的医生描绘了一幅令人担忧的画面，即康复后的患者患有永久性肺、心脏或肾脏损伤。在重症监护室接受治疗的患者的x射线图像显示肺纤维化——当肺组织受损和结疤时发生的一种慢性肺部疾病。肺纤维化可导致永久性呼吸短促（呼吸困难）、频繁干咳和疲劳。此外，随着肺纤维化的发展，它可能导致并发症，如肺部血栓形成、肺部感染和肺癌。这项提议的目标是模拟感染诱导的肺纤维化，并使用Rheolution的非侵入性机械测试仪量化感染期间组织增厚和刚度增加的演变。为了实现这一目标，我们将与我们的工业合作伙伴Rheolution公司合作，通过实时测量工程组织的机械性能来概括肺部感染的病理生理学，并监测组织刚度的演变。此外，我们将评估几种候选抗炎药在预防纤维组织形成方面的预防效率。这项工作的应用不仅限于COVID-19。该平台可用于其他类型的肺部感染、慢性阻塞性肺疾病、慢性呼吸衰竭和肺癌。该项目的结果不仅对理解疾病进展的机制及其对肺损伤的长期影响具有重要意义，而且可以作为评估未来将出现的新型抗病毒和抗纤维化药物有效性的有力工具。

As the world's effort is currently centered on "flattening the curve" by practicing social distancing, performing widespread testing, and developing new drugs and vaccines, dealing long-term health issues for patients who recovered from the disease has become the next primary concern. Doctors who are leading clinical research projects on the long-term consequences of COVID-19 are drawing a worrying picture of recovered patients with permanent lung, hearth, or kidney damage. X-Ray images of patients who have been treated in intensive care are showing pulmonary fibrosis-a chronic lung disease that occurs when lung tissue becomes damaged and scarred. Pulmonary fibrosis can lead to permanent shortness of breath (dyspnea), frequent dry cough, and fatigue. Furthermore, as pulmonary fibrosis progresses, it may lead to complications such as blood clots forming in the lungs, lung infections, and lung cancer. The goal of this proposal is to model infection-induced pulmonary fibrosis and quantify the evolution of tissue thickening and increased stiffness during infection using Rheolution's non-invasive mechanical tester. To achieve this goal, we will collaborate with our industrial partner, Rheolution Inc., to recapitulate the pathophysiology of lung infection and monitor the evolution of tissue stiffness by real-time measurement of the mechanical properties of the engineered tissue. Furthermore, we will evaluate the prophylaxis efficiency of a few anti-inflammatory drug candidates in preventing the formation of fibrous tissue in the developed model. The application of this work is not limited to COVID-19. This platform can be used for other types of pulmonary infections, chronic obstructive pulmonary diseases, chronic respiratory failure, and lung cancer. The outcomes of this project will have significant implications not only in understanding the mechanisms underlying the disease progression and its long-term effects on the lung damage, but it can serve as a powerful tool for evaluating the effectiveness of novel antiviral and anti-fibrosis drugs that will be emerged in the future.