Using Microfluidics to Align Matrix Architecture and Generate Chemokine Gradients Promotes Directional Branching in a...

Area of Science:

• Biomaterials Science
• Developmental Biology
• Tissue Engineering

Background:

• Fiber alignment is crucial for tissue development, but in vitro study has been limited.
• Existing methods lack the ability to precisely control mechanical cues and biochemical gradients.

Purpose of the Study:

• To develop a novel microfluidic device for studying the effects of mechanical cues on tissue development.
• To enable the investigation of cell responses to tunable interstitial fluid flow and morphogen gradients.
• To model complex tissues and understand cellular behavior in a controlled environment.

Main Methods:

• A microfluidic device was designed to intrinsically generate aligned fibers using microchannel geometry.
• The device incorporates tunable interstitial fluid flow and the capability to form a morphogen gradient.
• Luminal epithelial cysts were cultured within the device and subjected to growth factor stimulation.

Main Results:

• The mechanical cue of fiber alignment was found to be a dominant factor in cell elongation.
• The formation of cell protrusions was identified as being dependent on cadherin-3.
• The device successfully modeled complex tissue development and differentiated cell responses to stimuli.

Conclusions:

• This microfluidic device offers a powerful platform for investigating developmental biology and complex diseases.
• The findings highlight the significant role of mechanical cues in tissue development and cell behavior.
• Future applications include studying cancer biology and regenerative medicine.