Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, Colorado.
Cardiovascular Pulmonary Research Laboratories, University of Colorado, Anschutz Medical Campus, Aurora, Colorado.
Am J Physiol Lung Cell Mol Physiol. 2019 Feb 1;316(2):L303-L320. doi: 10.1152/ajplung.00353.2018. Epub 2018 Nov 21.
Chronic pulmonary diseases, including idiopathic pulmonary fibrosis (IPF), pulmonary hypertension (PH), and chronic obstructive pulmonary disease (COPD), account for staggering morbidity and mortality worldwide but have limited clinical management options available. Although great progress has been made to elucidate the cellular and molecular pathways underlying these diseases, there remains a significant disparity between basic research endeavors and clinical outcomes. This discrepancy is due in part to the failure of many current disease models to recapitulate the dynamic changes that occur during pathogenesis in vivo. As a result, pulmonary medicine has recently experienced a rapid expansion in the application of engineering principles to characterize changes in human tissues in vivo and model the resulting pathogenic alterations in vitro. We envision that engineering strategies using precision biomaterials and advanced biomanufacturing will revolutionize current approaches to disease modeling and accelerate the development and validation of personalized therapies. This review highlights how advances in lung tissue characterization reveal dynamic changes in the structure, mechanics, and composition of the extracellular matrix in chronic pulmonary diseases and how this information paves the way for tissue-informed engineering of more organotypic models of human pathology. Current translational challenges are discussed as well as opportunities to overcome these barriers with precision biomaterial design and advanced biomanufacturing techniques that embody the principles of personalized medicine to facilitate the rapid development of novel therapeutics for this devastating group of chronic diseases.
慢性肺部疾病，包括特发性肺纤维化（IPF）、肺动脉高压（PH）和慢性阻塞性肺疾病（COPD），在全球范围内导致了惊人的发病率和死亡率，但可供选择的临床治疗方法有限。尽管在阐明这些疾病的细胞和分子途径方面已经取得了巨大进展，但基础研究努力与临床结果之间仍存在显著差距。这种差异部分归因于许多当前疾病模型未能重现体内发病过程中发生的动态变化。因此，肺部医学最近在将工程原理应用于描述体内人类组织的变化以及在体外模拟由此产生的致病改变方面取得了快速发展。我们设想，使用精密生物材料和先进生物制造的工程策略将彻底改变当前的疾病建模方法，并加速个性化治疗的开发和验证。这篇综述强调了肺部组织特征分析如何揭示慢性肺部疾病中细胞外基质的结构、力学和组成的动态变化，以及这些信息如何为更具器官样特征的人类病理学模型的组织信息工程铺平道路。本文还讨论了当前的转化挑战，以及如何通过精密生物材料设计和先进的生物制造技术来克服这些障碍，这些技术体现了个性化医疗的原则，以促进为这一组严重的慢性疾病开发新型治疗方法。
