The blood-brain barrier (BBB) is a critical structure that serves as the gatekeeper between the central nervous system and the rest of the body. It is the responsibility of the BBB to facilitate the entry of required nutrients into the brain and to exclude potentially harmful compounds; however, this complex structure has remained difficult to model faithfully in vitro. Accurate in vitro models are necessary for understanding how the BBB forms and functions, as well as for evaluating drug and toxin penetration across the barrier. Many previous models have failed to support all the cell types involved in the BBB formation and/or lacked the flow-created shear forces needed for mature tight junction formation. To address these issues and to help establish a more faithful in vitro model of the BBB, we have designed and fabricated a microfluidic device that is comprised of both a vascular chamber and a brain chamber separated by a porous membrane. This design allows for cell-to-cell communication between endothelial cells, astrocytes, and pericytes and independent perfusion of both compartments separated by the membrane. This NeuroVascular Unit (NVU) represents approximately one-millionth of the human brain, and hence, has sufficient cell mass to support a breadth of analytical measurements. The NVU has been validated with both fluorescein isothiocyanate (FITC)-dextran diffusion and transendothelial electrical resistance. The NVU has enabled in vitro modeling of the BBB using all human cell types and sampling effluent from both sides of the barrier.

Organs-on-a-Chip (OOAC) is a disruptive technology with widely recognized potential to change the efficiency, effectiveness, and costs of the drug discovery process; to advance insights into human biology; to enable clinical research where human trials are not feasible. However, further development is needed for the successful adoption and acceptance of this technology. Areas for improvement include technological maturity, more robust validation of translational and predictive in vivo-like biology, and requirements of tighter quality standards for commercial viability. In this review, we reported on the consensus around existing challenges and necessary performance benchmarks that are required toward the broader adoption of OOACs in the next five years, and we defined a potential roadmap for future translational development of OOAC technology. We provided a clear snapshot of the current developmental stage of OOAC commercialization, including existing platforms, ancillary technologies, and tools required for the use of OOAC devices, and analyze their technology readiness levels. Using data gathered from OOAC developers and end-users, we identified prevalent challenges faced by the community, strategic trends and requirements driving OOAC technology development, and existing technological bottlenecks that could be outsourced or leveraged by active collaborations with academia.