Microtube-embedded microfluidic devices for potential applications in blood brain barrier research

The blood-brain barrier (BBB) is a distinct feature in the human body that blocks toxicants from the brain and preserves the homeostasis of the central nerve system. This barrier, however, also prevents efficient drug penetration for most of central neural system (CNS) disorders, including brain cancer, Parkinson's disease, and Alzheimer's disease. Development of robust and cost-effective in vitro BBB models is essential to enhance the efficiency of brain drug screening. Microfluidics-based in vitro models, also known as tissue/organ-on-chip, have emerged as a popular therapeutic tool due to the capability of creating a tunable dynamic extracellular microenvironment. The main challenge of fabricating BBB-on-chip is to recapitulate the tubular capillary structure. This paper presents two novel fabrication methods to mimic the brain capillary vessels in polydimethylsiloxane (PDMS) based microfluidic devices. In the first approach, polycaprolactone (PCL) coated sugar microfibers were embedded in PDMS chambers. The sugar core was then dissolved to create a microtube. In the second approach, polycaprolactone (PCL) microtubes were fabricated by core-sheath electrospinning and embedded in a bridge between two PDMS reservoirs. Both fabrication methods were successful in creating tubular microchannels which closely resemble the geometry of human capillaries. We expect that these microtube embedded microfluidic devices will allow the formation of 3D biomimetic neurovascular unit to study the human BBB for therapeutics development.