Pulmonary fibrosis includes several lung disorders characterized by scar formation and Idiopathic Pulmonary Fibrosis (IPF) is a particularly severe form of pulmonary fibrosis of unknown etiology with a mean life expectancy of 3 years' post-diagnosis. Treatments for IPF are limited to two FDA approved drugs, pirfenidone and nintedanib. Most lead candidate drugs that are identified in pre-clinical animal studies fail in human clinical trials. Thus, there is a need for advanced humanized in vitro models of the lung to improve candidate treatments prior to moving to human clinical trials. The development of 3D tissue models has created systems capable of emulating human lung structure, function, and cell and matrix interactions. The specific models accomplish these features and preliminary studies conducted using some of these systems have shown potential for in vitro anti-fibrotic drug testing. Further characterization and improvements will enable these tissue models to extend their utility for in vitro drug testing, to help identify signaling pathways and mechanisms for new drug targets, and potentially reduce animal models as standard pre-clinical models of study. In the current review, we contrast different in vitro models based on increasing dimensionality (2D, 2.5D and 3D), with added focus on contemporary 3D pulmonary models of fibrosis.

肺纤维化包括几种以瘢痕形成为特征的肺部疾病，特发性肺纤维化（IPF）是病因不明的肺纤维化的一种特别严重的形式，平均预期寿命为诊断后3年。IPF的治疗仅限于两种FDA批准的药物，吡非尼酮和nintedanib。临床前动物研究中确定的大多数主要候选药物在人类临床试验中均未通过。因此，需要先进的体外人源化肺模型以改善候选治疗方法，然后再进行人体临床试验。3D组织模型的开发创造了能够模拟人肺结构，功能以及细胞和基质相互作用的系统。具体的模型实现了这些功能，使用其中一些系统进行的初步研究显示了体外抗纤维化药物测试的潜力。进一步的表征和改进将使这些组织模型能够扩展其在体外药物测试中的效用，帮助确定新药物靶标的信号传导途径和机制，并有可能减少作为标准临床前研究模型的动物模型。在当前的评论中，我们对比了不同的体外 基于增加的维度（2D，2.5D和3D）的模型，并重点关注当代3D肺纤维化肺模型。