Novel vascular-like BBB-on-a-chip

ended

There is great need to develop safer and more biologically relevant models for drug screening. Recent reports indicate that up to 20% of acute kidney complications can be linked to drug-induced nephrotoxicity and more than 40 molecules found to reduce Alzheimer’s Disease (AD)-related plaques in animal models were shown to be ineffective in AD patients. It is increasingly evident that both in vitro and in vivo models being used to develop drugs have a limited capacity to predict the pathophysiology of human disease, personalized response, and off-target drug toxicity. The inability to properly test drugs and treatments to diseases such as AD constitutes a risk for pharmaceutical companies and a major obstacle to overcome. This ERC PoC proposal aims to establish a practical microfluidic fabrication process capable of recreating structural and biomechanical features of native blood vessels. Specifically, we aim to develop a scalable 3D Blood-Brain-Barrier in vitro model (BBB-on-a-chip) able to provide a higher level of biological relevance than current in vitro models. The development of such a system would represent a major break-through for the pharmaceutical industry generating therapies for a variety of neurological disorders. Thanks to the ERC Starting Grant STROFUNSCAFF, we have developed a simple fabrication process that combines bioprinting and self-assembly to grow functional fluidic devices with endothelialized vessel-like capillaries (patent application in preparation). NOVACHIP proposes to a) build scalable microfluidic devices made from capillaries that incorporate relevant cells and extracellular matrix (ECM) components, exhibit tissue-like stiffness, and can be designed with specific sizes and geometries to better resemble the native BBB and b) compare it to a commercially available in vitro model as well as c) an established rat model by quantifying permeability of specific imaging biomarkers for Magnetic Resonance Imaging (MRI) technique.