Recreating cellular barriers in human microphysiological systems in-vitro.

Area of Science:

• Biomaterials Engineering
• Cellular Biology
• Neuroscience

Background:

• Cellular barriers, like the blood-brain barrier (BBB), are crucial for physiological regulation.
• Existing in-vitro models often fail to accurately replicate basement membrane (BM) thickness and diffusion properties.
• Accurate BBB models are vital for understanding neurodegenerative diseases and developing targeted therapies.

Purpose of the Study:

• To engineer a porous polymeric nanofilm to replicate the basement membrane in a microfluidic blood-brain barrier model.
• To assess the biocompatibility and structural integrity of the nanofilm for cellular barrier applications.
• To establish a robust microfluidic system for high-throughput investigation of the BBB.

Main Methods:

• Fabrication of porous poly(D-L-lactic acid) (PDLLA) nanofilms with controlled thickness and pore size.
• Culture of human umbilical vein endothelial cells (HUVECs) on PDLLA nanofilms.
• Assessment of cell viability and morphology.
• Integration of nanofilms into a microfluidic device with two chambers, evaluating sealing and leakage.

Main Results:

• PDLLA nanofilms exhibited an average thickness of [Formula: see text] and a maximum pore diameter of 1.6 μm.
• HUVECs cultured on PDLLA showed >95% viability and normal morphology after 7 days.
• A microfluidic system integrating the nanofilm demonstrated effective sealing without leakage.

Conclusions:

• PDLLA nanofilms provide a viable biomimetic material for recreating basement membranes in microfluidic cellular barrier models.
• This engineered blood-brain barrier model offers a physiologically relevant platform for neurodegenerative disease research.
• The model facilitates cruelty-free, high-throughput drug screening for brain-targeted therapies.