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For centuries, animal experiments have contributed much to our understanding of mechanisms of human disease, but their value in predicting the effectiveness of drug treatments in the clinic has remained controversial. Animal models, including genetically modified ones and experimentally induced pathologies, often do not accurately reflect disease in humans, and therefore do not predict with sufficient certainty what will happen in humans. Organ-on-chip (OOC) technology and bioengineered tissues have emerged as promising alternatives to traditional animal testing for a wide range of applications in biological defence, drug discovery and development, and precision medicine, offering a potential alternative. Recent technological breakthroughs in stem cell and organoid biology, OOC technology, and 3D bioprinting have all contributed to a tremendous progress in our ability to design, assemble and manufacture living organ biomimetic systems that more accurately reflect the structural and functional characteristics of human tissue in vitro, and enable improved predictions of human responses to drugs and environmental stimuli. Here, we provide a historical perspective on the evolution of the field of bioengineering, focusing on the most salient milestones that enabled control of internal and external cell microenvironment. We introduce the concepts of OOCs and Microphysiological systems (MPSs), review various chip designs and microfabrication methods used to construct OOCs, focusing on blood-brain barrier as an example, and discuss existing challenges and limitations. Finally, we provide an overview on emerging strategies for 3D bioprinting of MPSs and comment on the potential role of these devices in precision medicine.

Objective Ventricular assist devices (VADs) increase waitlist survival, yet the risk of stroke remains notable. The purpose of this study was to analyze how strokes on VAD support impact post‐transplant (post‐Tx) outcomes in children. Methods About 520 pediatric (<18 years) heart transplant candidates listed from January 2011 to April 2018 with a VAD implant date were matched between the United Network of Organ Sharing and Pediatric Health Information System databases. Patients were divided into pre‐Tx Stroke and No Stroke cohorts. Results About 81% of the 520 patients were transplanted; 28% (n = 146) had a pre‐Tx Stroke; and 59% (n = 89) of the Stroke patients were transplanted at a median of 57 (IQR 17–102) days from stroke. Significantly more No Stroke cohort (90%) were transplanted (p < 0.001). There was no difference in post‐Tx survival between the Stroke and No Stroke cohorts (p = 0.440). Time between stroke and transplant for patients who died within 1 year of transplant was 32.0 days (median) compared to 60.5 days for those alive >1 year (p = 0.18). Regarding patients in whom time from stroke to transplant was more than 60 days, one‐year survival of Stroke vs. No Stroke patients was 96% vs. 95% (p = 0.811), respectively. Conclusion Patients with stroke during VAD support, once transplanted, enjoy similar survival compared to No Stroke patients. We hypothesize that allowing Stroke patients more time to recover could improve post‐Tx outcomes. Unfortunately, the ideal duration of time between stroke and safe transplantation could not be determined and will require more detailed and larger studies in the future.

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