Cell Culture Insert-Mountable Lung-on-a-chip for the Inkjet Bioprinted Alveolar Model

Abstract

Organ-on-a-chip is an emerging technology that can biomimic the dynamic microenvironment and key functions of organ units. Although various organ-on-chips have been developed through the efforts of numerous researchers, most of them have closed structures with a porous membrane in the middle. Injection of cell suspension is generally used to seed cells inside a closed structured chip, but controlling the number of cells or distributing cells uniformly is challenging. As a way to overcome these limitations, we constructed an open-structured chip in a form that can integrate with commercial cell culture inserts. The fabricated open-structured organ-on-a-chip was used for culturing the previously developed inkjet bioprinted alveolar barrier model for biomimetic blood flow at the epithelial-blood barrier interface. The results show that the 3D structured model maintained distinct three thin layers and the tight junction of the epithelial layer, which are the key properties of alveoli, in the process of being cultured in the chip. Additionally, the upregulation of genes involved in alveolar respiratory function was confirmed. Our open-structured organ-on-a-chip is an innovative platform that can be applied to various types of organ models by simply mounting and interchanging cell culture inserts. In particular, it will be advantageous for mass production and the development of customized models through convergence with bioprinting technology.2