The California Institute for Quantitative Biosciences, Stanley Hall, University of California, Berkeley, Berkeley, CA, 94720, USA.
Department of Mechanical Engineering, University of California, Berkeley, Berkeley, CA, 94720, USA.
Adv Healthc Mater. 2018 Jun;7(12):e1800122. doi: 10.1002/adhm.201800122. Epub 2018 Apr 26.
Engineering physiologically relevant in vitro models of human organs remains a fundamental challenge. Despite significant strides made within the field, many promising organ-on-a-chip models fall short in recapitulating cellular interactions with neighboring cell types, surrounding extracellular matrix (ECM), and exposure to soluble cues due, in part, to the formation of artificial structures that obstruct >50% of the surface area of the ECM. Here, a 3D cell culture platform based upon hydrophobic patterning of hydrogels that is capable of precisely generating a 3D ECM within a microfluidic channel with an interaction area >95% is reported. In this study, for demonstrative purposes, type I collagen (COL1), Matrigel (MAT), COL1/MAT mixture, hyaluronic acid, and cell-laden MAT are formed in the device. Three potential applications are demonstrated, including creating a 3D endothelium model, studying the interstitial migration of cancer cells, and analyzing stem cell differentiation in a 3D environment. The hydrophobic patterned-based 3D cell culture device provides the ease-of-fabrication and flexibility necessary for broad potential applications in organ-on-a-chip platforms.
工程化生理相关的人体器官体外模型仍然是一个基本的挑战。尽管在该领域取得了重大进展,但许多有前途的器官芯片模型在重现细胞与相邻细胞类型、周围细胞外基质 (ECM) 的相互作用以及对可溶性信号的暴露方面都存在不足,部分原因是由于形成了阻碍 ECM 表面积 >50%的人工结构。在这里,报告了一种基于水凝胶疏水性图案化的 3D 细胞培养平台,该平台能够在微流道内精确生成 >95%互作面积的 3D ECM。在这项研究中,出于演示目的,在设备中形成了 I 型胶原蛋白 (COL1)、Matrigel (MAT)、COL1/MAT 混合物、透明质酸和细胞负载的 MAT。展示了三种潜在的应用,包括创建 3D 内皮模型、研究癌细胞的间质迁移以及在 3D 环境中分析干细胞分化。基于疏水性图案化的 3D 细胞培养装置提供了在器官芯片平台中广泛应用所需的易于制造和灵活性。