Native extracellular matrix-derived semipermeable, optically transparent, and inexpensive membrane inserts for...

Area of Science:

• Biomaterials Engineering
• Cell Biology
• Microfluidics

Background:

• Current microfluidic cell culture membranes use synthetic polymers, limiting mimicry of native cellular environments.
• Native extracellular matrices (ECM) are crucial for inducing physiological cell phenotypes but are difficult to integrate into microdevices.
• Existing synthetic membranes fail to fully replicate the complex cell-ECM interactions vital for in vitro models.

Purpose of the Study:

• To engineer novel, thin, semipermeable cell culture membranes from native extracellular matrix (ECM) materials.
• To integrate these ECM membranes into microfluidic devices for advanced cell culture applications.
• To demonstrate the biological activity and physiological relevance of ECM-based membranes compared to synthetic ones.

Main Methods:

• Fabrication of ECM membranes via controlled sequential vitrification of 3D ECM hydrogels into stable thin films.
• Modulation of ECM composition to tune membrane properties like optical transparency, stiffness, and porosity.
• Integration of ECM membranes into multilayered microfluidic devices for compartmentalized cell culture.

Main Results:

• ECM membranes successfully supported the attachment and growth of epithelial, endothelial, and mesenchymal cells under perfusion.
• Demonstrated promotion of adhesion-associated intracellular signaling, crucial for cell-ECM interactions.
• Successfully utilized ECM membranes to induce physiological tissue differentiation and model tissue interfaces in microfluidic systems.

Conclusions:

• Engineered ECM membranes offer a biologically active and tunable platform for microfluidic cell culture.
• These membranes serve as effective alternatives to synthetic inserts, enhancing physiological relevance in vitro.
• The developed approach provides a robust strategy for creating advanced cell culture models for diverse applications.