Investigational New Drug-enabling studies in a human vessel-chip: Are we there yet?

The US Food and Drug Administration (FDA) Modernization Act 3.0, and the announcement of an National Institutes of Health (NIH)-wide Office of Research Innovation, Validation, and Application has increased funding for, and encouraged development of, human avatars for disease modeling and drug discovery. This pivotal change has sparked excitement among engineers, scientists, and industry stakeholders to utilize microphysiological systems—also known as organ-chips—as viable alternative platforms that may be alternatives to animal models in replicating human pathophysiology. The promise of such systems is that they will be more predictive of clinical responses to novel therapeutic interventions. Furthermore, such systems lend themselves to relatively more patient-specific approaches. These human chips might support precision medicine by predicting response to drugs and therapies—in early clinical trial phases or perhaps even at the bedside. However, for vascular avatars to be useful in preclinical drug development or in clinical trial refinement, several technical, scientific, and educational barriers remain to be addressed. This review highlights the current advancements, potential, and challenges in leveraging vessel-chip technologies to accelerate vascular medicine and drug discovery, raising the prospect of more rapid FDA investigational new drug approvals and efficient clinical trials.