Iriondo Cinta, Koornneef Sem, Skarp Kari-Pekka, Buscop-van Kempen Marjon, Boerema-de Munck Anne, Rottier Robbert J
Department of Pediatric Surgery, Sophia Children's Hospital, Erasmus Medical Center, Rotterdam 3000 CB, The Netherlands.
Department of Cell Biology, Erasmus Medical Center, Rotterdam 3000 CB, The Netherlands.
ACS Biomater Sci Eng. 2025 Jan 13;11(1):451-462. doi: 10.1021/acsbiomaterials.4c01322. Epub 2024 Dec 24.
Immortalized epithelial cell lines and animal models have been used in fundamental and preclinical research to study pulmonary diseases. However valuable, though, these models incompletely recapitulate the human lung, which leads to low predictive outcomes in potential respiratory treatments. Advanced technology and cell culture techniques stimulate the development of improved models that more closely mimic the physiology of the human lung. Nonetheless, most of these models are technically demanding and have a low throughput and reproducibility. Here, we describe a robust fluidic device consisting of a biocompatible and customizable 3D-printed cell culture plate, the Simple-Flow, which has medium throughput, is simple to manufacture, and is easy to set up. As a proof of principle, human primary bronchial epithelial cells (hPBECs) and human pulmonary microvascular endothelial cells (hMVECs) were cocultured on the apical and basolateral sides of the inset membranes, respectively. While hPBECs were cultured at the air-liquid interface to induce mucociliary differentiation, hMVECs were exposed to flow medium for up to 2 weeks. We show the versatility of 3D-printing technology in designing models for cell culturing applications, such as pediatric lung diseases or other pulmonary disorders.
永生化上皮细胞系和动物模型已被用于基础研究和临床前研究，以研究肺部疾病。然而，尽管这些模型很有价值，但它们并不能完全重现人类肺部的情况，这导致在潜在的呼吸治疗中预测结果较低。先进的技术和细胞培养技术推动了更能模拟人类肺生理功能的改良模型的发展。尽管如此，这些模型大多技术要求高，通量低且可重复性差。在此，我们描述了一种坚固的流体装置，它由一个生物相容性且可定制的3D打印细胞培养板（Simple-Flow）组成，该装置通量适中，制造简单且易于设置。作为原理验证，人原代支气管上皮细胞（hPBECs）和人肺微血管内皮细胞（hMVECs）分别在嵌入膜的顶端和基底外侧共培养。当hPBECs在气液界面培养以诱导黏液纤毛分化时，hMVECs暴露于流动培养基中长达2周。我们展示了3D打印技术在设计用于细胞培养应用（如儿科肺部疾病或其他肺部疾病）模型方面的多功能性。
