Ultra-thin and ultra-porous nanofiber networks as a basement-membrane mimic

• Published in: Lab on a chip Vol. 23; no. 20; p. 4565
• Main Authors: Graybill, Philip M, Jacobs, 4th, Edward J, Jana, Aniket, Agashe, Atharva, Nain, Amrinder S, Davalos, Rafael V
• Format: Journal Article
• Language: English
• Published: England 10-10-2023
• Subjects: Basement Membrane; Blood-Brain Barrier - physiology; Coculture Techniques; Nanofibers; Porosity
• ISSN: 1473-0189
• DOI: 10.1039/d3lc00304c

Current basement membrane (BM) mimics used for modeling endothelial and epithelial barriers
do not faithfully recapitulate key
physiological properties such as BM thickness, porosity, stiffness, and fibrous composition. Here, we use networks of precisely arranged nanofibers to form ultra-thin (∼3 μm thick) and ultra-porous (∼90%) BM mimics for blood-brain barrier modeling. We show that these nanofiber networks enable close contact between endothelial monolayers and pericytes across the membrane, which are known to regulate barrier tightness. Cytoskeletal staining and transendothelial electrical resistance (TEER) measurements reveal barrier formation on nanofiber membranes integrated within microfluidic devices and transwell inserts. Further, significantly higher TEER values indicate a biological benefit for co-cultures formed on the ultra-thin nanofiber membranes. Our BM mimic overcomes critical technological challenges in forming co-cultures that are in proximity and facilitate cell-cell contact, while still being constrained to their respective sides. We anticipate that our nanofiber networks will find applications in drug discovery, cell migration, and barrier dysfunction studies.