Physiological Relevance of Engineered Brain Models

Abstract

Engineered brain models, including brain organoids and brain-on-a-chip systems, are generally assessed in terms of their physiological relevance. Although this language is useful for emphasizing the need to better approximate human biology, it can also obscure important differences among context of use, required validation strategy and ethical considerations. In this Opinion, we argue that physiological relevance should not be treated as a universal measure of model quality. Instead, its meaning should be defined relative to its application domain, including animal-model comparison, interpretation of single-cell atlases, clinical translation, donor representation, and emerging functional app..