Reconfigurable Microphysiological Systems for Modeling Innervation and Multitissue Interactions.

Area of Science:

• Biomedical Engineering
• Tissue Engineering
• Microfluidics

Background:

• Tissue-engineered models face challenges in structural specificity, nutrient delivery, and cellular heterogeneity, particularly for metabolically demanding organs like the heart.
• Existing methods like soft lithography have limitations in recapitulating complex biological architectures.

Purpose of the Study:

• To develop a reconfigurable, inexpensive microphysiological system (MPS) for improved 3D cell compartmentalization and nutrient transport.
• To demonstrate the MPS's capability in replicating complex organ microenvironments for functional assessment.

Main Methods:

• Utilized microfluidics, tissue engineering, and layer-by-layer fabrication with meniscus pinning, photocrosslinkable hydrogels, and laser engraving.
• Designed complex, multilayered systems with integrated instrumentation for real-time monitoring.
• Replicated the cardiac sympathetic nervous system's 3D microenvironment.

Main Results:

• The developed MPS demonstrated discrete 3D cell compartmentalization and enhanced nutrient transport.
• Sympathetic-cardiac co-culture in the MPS increased spontaneous cardiac beat rate.
• Drug-induced increases in cardiac beating correlated with greater sympathetic innervation.

Conclusions:

• This low-cost, robust fabrication technique offers a versatile platform for creating complex, multilayered microphysiological systems.
• The demonstrated cardiac sympathetic nervous system model shows promise for drug screening, discovery, and personalized medicine applications.
• The methodology is adaptable for engineering other organ systems.