Understanding parasite-brain microvascular interactions with engineered 3D blood-brain barrier models.

Microbial interactions with the blood-brain barrier (BBB) can be highly pathogenic and are still not well understood. Among these, parasites present complex interactions with the brain microvasculature that are difficult to decipher using experimental animal models or reductionist 2D in vitro cultures. Novel 3D engineered blood-brain barrier models hold great promise to overcome limitations in traditional research approaches. These models better mimic the intricate 3D architecture of the brain microvasculature and recapitulate several aspects of BBB properties, physiology, and function. Moreover, they provide improved control over biophysical and biochemical experimental parameters and are compatible with advanced imaging and molecular biology techniques. Here, we review design considerations and methodologies utilized to successfully engineer BBB microvessels. Finally, we highlight the advantages and limitations of existing engineered models and propose applications to study parasite interactions with the BBB, including mechanisms of barrier disruption.