Salimbeigi Golestan, Vrana Nihal E, Ghaemmaghami Amir M, Huri Pinar Y, McGuinness Garrett B
School of Mechanical and Manufacturing Engineering, Dublin City University, Dublin 9, Ireland.
Spartha Medical, 14B Rue de la Canardiere, 67100, Strasbourg, France.
Mater Today Bio. 2022 May 23;15:100301. doi: 10.1016/j.mtbio.2022.100301. eCollection 2022 Jun.
Drug discovery and toxicology is a complex process that involves considerable basic research and preclinical evaluation. These depend highly on animal testing which often fails to predict human trial outcomes due to species differences. Coupled with ethical concerns around animal testing, this leads to a high demand for improved cell culture platforms. Current research efforts, in this regard, however, are facing a challenge to provide physiologically relevant human organ models for a reliable assessment of the physiological responses of the body to drug compounds and toxins. The latest development in cell culture models, organ-on-chips (OOCs), seek to introduce more realistic models of organ function. Current OOCs often use commercial porous polymeric membranes as a barrier membrane for cell culture which is challenging due to the poor replication of the physiological architectures. Better recapitulation of the native basement membrane (BM) characteristics is desirable for modelling physical (e.g. intestine, skin and lung) and metabolic (e.g. liver) barrier models. In this review, the relevance of the physical and mechanical properties of the membrane to cell and system behaviour is elucidated. Key parameters for replicating the BM are also described. This review provides information for future development of barrier organ models focusing on BM-mimicking substrates as a core structure.
药物发现与毒理学是一个复杂的过程，涉及大量的基础研究和临床前评估。这些高度依赖动物试验，但由于物种差异，动物试验往往无法预测人体试验结果。再加上围绕动物试验的伦理问题，这导致对改进细胞培养平台的需求很高。然而，目前这方面的研究工作面临着一个挑战，即要提供生理相关的人体器官模型，以便可靠地评估身体对药物化合物和毒素的生理反应。细胞培养模型的最新发展，即器官芯片（OOC），试图引入更逼真的器官功能模型。目前的器官芯片通常使用商业多孔聚合物膜作为细胞培养的屏障膜，由于生理结构的复制性差，这具有挑战性。为了模拟物理（如肠道、皮肤和肺）和代谢（如肝脏）屏障模型，更好地再现天然基底膜（BM）的特征是可取的。在这篇综述中，阐明了膜的物理和机械性能与细胞和系统行为的相关性。还描述了复制基底膜的关键参数。这篇综述为以模仿基底膜的底物作为核心结构的屏障器官模型的未来发展提供了信息。
