Resilience to bioprinting-induced cellular stress by heat shock preconditioning

Bioprinting holds the promise to revolutionize therapeutic development and healthcare; however, we still lack an in-depth understanding of how cells respond to stress experienced during the bioprinting process. Here, we assess at the molecular and cellular level the effects of bioprinting-induced stress on cell morphology, metabolism, and behavior using human umbilical vein endothelial cells. We demonstrate that mild preconditioning of the stress response in cells using heat shock before bioprinting helps cells to rapidly respond to bioprinting-associated stress, mitigating negative effects. We hypothesize this is in part mediated by the small heat shock protein 27 (Hsp27) which is known to play a role in stabilizing actin in the cytoskeleton. This results in restoration of cellular viability, morphology, metabolism, and function, including vascularization. Our study outlines an easy-to-implement strategy to improve cell viability following bioprinting, facilitating the real-life application of bioprinting.