3D Inkjet-Bioprinted Lung-on-a-Chip.

ABSTRACT

There is an urgent need for physiologically relevant and customizable biochip models of human lung tissue to provide a niche for lung disease modeling and drug efficacy. Although various lung-on-a-chips have been developed, the conventional fabrication method has been limited in reconstituting a very thin and multilayered architecture and spatial arrangements of multiple cell types in a microfluidic device. To overcome these limitations, we developed a physiologically relevant human alveolar lung-on-a-chip model, effectively integrated with an inkjet-printed, micron-thick, and three-layered tissue. After bioprinting lung tissues inside four culture inserts layer-by-layer, the inserts are implanted into a biochip that supplies a flow of culture medium. This modular implantation procedure enables the formation of a lung-on-a-chip to facilitate the culture of 3D-structured inkjet-bioprinted lung models under perfusion at the air-liquid interface. The bioprinted models cultured on the chip maintained their structure with three layers of tens of micrometers and achieved a tight junction in the epithelial layer, the critical properties of an alveolar barrier. The upregulation of genes involved in the essential functions of alveoli was also confirmed in our model. Our culture insert-mountable organ-on-a-chip is a versatile platform that can be applied to various organ models by implanting and replacing culture inserts. It is amenable to mass production and the development of customized models through the convergence with bioprinting technology.