An intact basement membrane provides structural support to the cells and is also critical in delivering communicative signals between the intravascular components and the glial/neuronal cells in addition to nutritional support from the blood stream 6. The basement membrane is composed of extracellular matrix molecules such as type IV collagen, laminins, fibronectin, heparan sulfates, and proteoglycans. The astrocyte endfeet form an envelope around the blood vessels and are attached to the basement membrane tightly by their adhesion molecules. The BBB is formed by capillary endothelial cells, surrounded by basal lamina and astrocytic perivascular endfeet with astrocytes providing the cellular link to the neurons. A combination of physical and biochemical barriers establishes the BBB endothelium as quite distinct from other endothelia 1- 5. Physiologically, the BBB consists of an intricate network of vascular endothelial cells (ECs) that isolate the central nervous system (CNS) from systemic blood circulation except the circumventricular organs. Finally, transporter assay was successfully demonstrated in SyM-BBB indicating a functional model.ĭelivery of neuroprotective or therapeutic agents to specific regions of the brain presents a major challenge, largely due to the presence of the Blood-Brain Barrier (BBB). ![]() Biochemical analysis showed upregulation of tight junction molecules while permeation studies showed an intact BBB. In the present study, an immortalized Rat Brain Endothelial cell line (RBE4) was cultured in SyM-BBB with a perfusate of Astrocyte Conditioned Media (ACM). The individually addressable apical side is seeded with endothelial cells and the basolateral side can support neuronal cells or conditioned media. The chamber is designed in such a way as to permit the realization of side-by-side apical and basolateral compartments, thereby simplifying fabrication and facilitating integration with standard instrumentation. The SyM-BBB platform is comprised of a plastic, disposable and optically clear microfluidic chip with a microcirculation sized two-compartment chamber. To overcome these limitations, we have developed a microfluidics based Synthetic Microvasculature model of the Blood- Brain Barrier (SyM-BBB). ![]() These devices have several critical shortcomings (a) they do not reproduce critical microenvironmental parameters, primarily anatomical size or hemodynamic shear stress, (b) they often do not provide real-time visualization capability, and (c) they require a large amount of consumables. Current techniques for mimicking the Blood-Brain Barrier (BBB) largely use incubation chambers (Transwell) separated with a filter and matrix coating to represent and to study barrier permeability.
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