Pulsed Microfluid Force-Based On-Chip Modular Fabrication for Liver Lobule-Like 3D Cellular Models

Area of Science:

• Tissue Engineering
• Regenerative Medicine
• Biotechnology

Background:

• In vitro three-dimensional (3D) cellular models are crucial for regenerative medicine and drug discovery.
• Replicating the liver's complex in vivo microenvironment, including its vascular network and heterogeneous cell distribution, remains a significant challenge in tissue engineering.

Purpose of the Study:

• To develop an on-chip 3D assembly method using pulsed microflow to create liver lobule-like models.
• To replicate the native spatial structure and functions of the liver lobule in vitro.

Main Methods:

• Fabrication of heterogeneous cell-laden assembly units via multistep photopatterning of hydrogels with hierarchical cell distribution.
• Utilizing pulsed microflow to drive assembly units into a stacked, layer-by-layer configuration within a closed liquid chamber.
• Implementing dynamic perfusion culture to sustain cell viability and function in the assembled 3D models.

Main Results:

• Successful construction of 3D liver lobule-like models exhibiting hexagonal morphology and radial cell distribution.
• Demonstrated high cell viability and sustained functional expression during long-term in vitro culture due to dynamic perfusion.
• Validation of the model's ability to mimic in vivo microenvironments and liver lobule structure.

Conclusions:

• The pulsed microflow-based 3D assembly method effectively creates functional, liver lobule-like models.
• These 3D liver models show significant potential for applications in drug testing, personalized medicine, and disease modeling.