Prospects and Limitations of Bioprinting in Studying Human Cells' Responses to Extreme Environments.

Understanding human's responses to extreme environments holds significant importance for space exploration, deep-sea research, and environmental adaptation. Traditionally, human subjects were used to study humans' responses to extreme environments. The main limitations of this approach include the inability to independently investigate specific cellular mechanisms, ethical and safety constraints, limited experimental controllability, and inter-individual variability that complicates mechanistic interpretation. Another approach is to study humans' responses at the cellular level using 2D culture. This approach often exhibits limited reproducibility due to its inability to recapitulate physiologically relevant microenvironments. Bioprinting can enable studies on human's responses at the cellular level and within 3D environments. One way is to study human cells' responses to localized and transient extreme environments created during printing. Another way is to expose 3D printed samples (embedded with human cells) to extreme environments. However, the literature does not contain comprehensive review papers to discuss the prospects and limitations of bioprinting for investigating human cells' responses to extreme environments. This review paper aims to fill this gap in the literature. It begins with a brief description of the effects of extreme environments on human health and summarizes reported studies on cells' responses to extreme environments. Afterward, it discusses the prospects and limitations of the two ways of using bioprinting to investigate cells' responses to extreme environments. Finally, it concludes with identifying knowledge gaps and proposing research directions in the application of bioprinting to study human cells' responses to extreme environments.