Abstract:
Fibrosis, which is primarily marked by excessive extracellular matrix (ECM) deposition, is a pathophysiological process associated with many disorders, which ultimately leads to organ dysfunction and poor patient outcomes. Despite the high prevalence of fibrosis, currently there exist few therapeutic options, and importantly, there is a paucity of in vitro models to accurately study fibrosis. This review discusses the multifaceted nature of fibrosis from the viewpoint of developing organ-on-chip (OoC) disease models, focusing on five key features: the ECM component, inflammation, mechanical cues, hypoxia, and vascularization. The potential of OoC technology is explored for better modeling these features in the context of studying fibrotic diseases and the interplay between various key features is emphasized. This paper reviews how organ-specific fibrotic diseases are modeled in OoC platforms, which elements are included in these existing models, and the avenues for novel research directions are highlighted. Finally, this review concludes with a perspective on how to address the current gap with respect to the inclusion of multiple features to yield more sophisticated and relevant models of fibrotic diseases in an OoC format.
摘要:
纤维化,其主要标志是过度的细胞外基质(ECM)沉积,是与许多疾病相关的病理生理过程,最终导致器官功能障碍和患者预后不良。尽管纤维化的患病率很高,目前很少有治疗选择,而且重要的是,缺乏准确研究纤维化的体外模型。这篇综述从发展器官芯片(OoC)疾病模型的角度讨论了纤维化的多面性,专注于五个关键特征:ECM组件,炎症,机械提示,缺氧,和血管化。在研究纤维化疾病的背景下,探索了OoC技术的潜力,以更好地对这些特征进行建模,并强调了各种关键特征之间的相互作用。本文回顾了如何在OoC平台上对器官特异性纤维化疾病进行建模,这些现有模型中包含哪些元素,并强调了新颖研究方向的途径。最后,这篇综述最后提出了如何解决目前在纳入多个特征以OoC格式产生更复杂和相关的纤维化疾病模型方面的差距的观点.