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.

Harnessing three-dimensional (3D) cell culture models for pulmonary infections: State of the art and future directions

“…This in vitro model was validated and used for exploring the molecular patterns and biology of the coronavirus (Tindle et al 2021 ). Several lung cancer organoid models have been developed from primary patient tissues and patient-derived xenografts (PDX) (M. Kim et al 2019 ; Li et al 2020 ; Shi et al 2020 ). Development of mouse lung organoids has been reported by Hai et al ( 2020 ).…”

Guiding organs-on-chips towards applications: a balancing act between integration of advanced technologies and standardization

“…By converging bioprinting technology with OoC platforms, the precise distribution of different cell types on physiologically relevant extracellular matrices can be achieved to maximize biomimicry, while allowing for fine control of biophysical culture parameters (Chliara et al, 2022). Bioprinting and microfluidic devices have been combined to establish a variety of humanized models, including tracheal (Park et al, 2018), liver (Lee et al, 2020), tumor (Yi et al, 2019), vascular (Zhang et al, 2016a), myocardium (Zhang et al, 2016b), kidney (Homan et al, 2016), lung (Kim et al, 2023), and placenta (Mandt et al, 1970) models. In addition to adjusted biomaterial complexity and spatial organization for the reproduction of organ features, the use of patient-specific primary cells is advantageous for capturing the heterogeneity of disease progression, as often observed in clinical settings (Loewa et al, 2023).…”

Organ bioprinting: progress, challenges and outlook

“…Kim et al . 88 employed piezoelectric inkjet technology to fabricate a three-layered lung alveolar tissue model, which contained HULEC-5a pulmonary endothelial cells, MRC-5 lung fibroblasts, and lung epithelial cells. Additionally, they designed a microfluidic biochip that could modularly connect with the printed tissue to provide a stable gas–liquid interface culture environment.…”