Developing an advanced gut on chip model enabling the study of epithelial cell/fibroblast interactions.

Area of Science:

• Biomaterials Science
• Gastroenterology
• Tissue Engineering

Background:

• Organoids are valuable for studying gut pathophysiology but lack the complex intestinal wall structure.
• Existing models do not fully replicate the multi-component nature of the intestinal wall.

Purpose of the Study:

• To develop an advanced gut-on-a-chip model that better mimics the in vivo intestinal environment.
• To enable co-culture of primary epithelial and stromal cells within a biomimetic scaffold.

Main Methods:

• Fabrication of a 3D collagen I scaffold with mouse gut topography and dimensions.
• Rigidification of the scaffold using a cytocompatible threose-based treatment.
• Co-culture of primary intestinal fibroblasts and epithelial organoids within the scaffold.
• Application of fluid shear stress for long-term epithelial culture.

Main Results:

• The scaffold successfully supported the co-culture of epithelial and stromal cells, mimicking the gut stromal compartment.
• Deposited organoids epithelialized the scaffold, forming a polarized epithelial monolayer.
• Proper segregation of dividing and differentiated cells along the crypt-villus axis was observed.
• Long-term culture of the intestinal epithelium was achieved under fluid shear stress.

Conclusions:

• The developed gut-on-a-chip model is a novel biomimetic tool that captures key features of gut complexity.
• This model provides a more accurate representation of the intestinal wall for studying gut pathophysiology.
• The platform holds potential for advancing research in gastrointestinal diseases and drug testing.