Design and fabrication of demountable 3D microphysiological systems for modeling barrier function and underlying...

Area of Science:

• Biotechnology
• Tissue Engineering
• Microfluidics

Background:

• Microphysiological systems (MPSs) show promise for replacing traditional biological models.
• Current organ-chip technologies face challenges in tissue analysis, harvest, and imaging, especially for multi-layer systems.
• Transitioning from PDMS to thermoplastics addressed manufacturing and scalability but introduced new system limitations.

Purpose of the Study:

• To present a novel, low-cost method for fabricating demountable organ-on-a-chip platforms.
• To overcome limitations in end-point tissue analysis and high-resolution imaging in current organ-chip systems.
• To enable rapid redesign and manufacture of alternative tissue and interface systems.

Main Methods:

• Fabrication of fluidically sealed but demountable organ chips using a cut-and-assemble method.
• Utilizing thermoplastics for layered 3D organ chips without cleanroom technologies.
• Culture of human aortic smooth muscle cells and iPSC-derived neural cells in GelMA hydrogel on chip for up to 27 days.

Main Results:

• Successful validation of the cut-and-assemble method for creating functional organ chips.
• Demonstrated long-term culture (27 days) of human cells within the 3D hydrogel environment.
• Enabled removal of 3D culture layers for high-resolution imaging via immunostaining.

Conclusions:

• The developed organ-chip platform offers a low-cost, accessible solution for advanced biological studies.
• This is the first innervated organ chip with removable layers and the first humanized nerve-artery model with 3D hydrogel culture.
• The platform's features are ideal for future investigations into cell crosstalk mechanisms in co-culture systems.