Simple design for membrane-free microphysiological systems to model the blood-tissue barriers

Area of Science:

• Biomedical Engineering
• Microfluidics
• Tissue Engineering

Background:

• Microphysiological systems (MPS) are crucial for mimicking tissue function in vitro.
• Existing blood-tissue interface (BTI) models often rely on membranes, homogenous cells, or 2D cultures, limiting their physiological relevance.
• Current BTI models face challenges in assembly and replicating 3D transport and direct endothelial-epithelial contact.

Purpose of the Study:

• To engineer a novel BTI-on-a-chip (BTI Chip) that overcomes limitations of current models.
• To develop a membrane-free, single-layer BTI chip design for enhanced physiological mimicry.
• To enable high-throughput generation of physiologically relevant MPS for research and industry.

Main Methods:

• Utilized laminar flow profiles and photocurable hydrogel scaffolds (gelatin methacryloyl and 8-arm polyethylene glycol thiol) for in situ tissue fabrication.
• Constructed a Y-shaped microfluidic device for rapid scaffold polymerization via UV light exposure.
• Seeded endothelial cells directly onto 3D engineered tissue scaffolds, creating epithelial and blood-brain barrier (BBB) models.

Main Results:

• Successfully fabricated a membrane-free BTI Chip with direct endothelial-3D tissue contact.
• Immunohistochemistry confirmed uniform endothelium juxtaposed with engineered tissue.
• Demonstrated physiological function and permeability using fluorescent tracers and an efflux pump inhibitor (cyclosporine A).

Conclusions:

• The developed BTI Chip offers a physiologically relevant, membrane-free microphysiological system.
• This novel design enables direct cell-cell interactions and 3D transport, crucial for accurate in vitro modeling.
• The BTI Chip facilitates high-throughput MPS generation for drug candidate screening and fundamental biological research.