A High-Throughput Open-Well System for Engineering Neurovascular Units

点击翻译按钮获取中文摘要

Project Summary Advances in engineering have provided unprecedented opportunities to control how cells are organized and interact in culture. Miniaturized fluidic systems containing a variety of cells in proper organization have been used to establish models of the essential units of a variety of human organs, including liver, lung, kidney, bone, etc. In the nervous system, these types of systems have been used to model the blood brain barrier, the neurovascular unit, and brain parenchyma. These systems hold great promise for advancing the understanding of fundamental human biology, for developing cures for disease, and for personalizing therapy for nervous system disorders. Additionally, they have the potential to decrease usage of rodents and other non-human animals in biological and medical research. One important technical challenge is that these systems can be complicated to operate, have limited reproducibility and robustness, and limited throughput. The proposed research aims to develop a system that results in an easy-to-use system, which enhances robustness and reproducibility, while maintaining high throughput and maintaining the important features—like a blood supply—that are important for the biological and medical utility of these biological models. We propose an open-well structure that allows easy access to cells and removes failure-prone tubing connections. We then propose to use this system to perform studies of the coupling between neurons and the brain blood vessels that they couple with. This coupling is important for proper functioning of the brain, and improper coupling has been implicated in neurodegenerative disease. By creating a simple-to-use system, we can begin to study this coupling much more easily, robustly, and reproducibly.