Microdevice array-based identification of distinct mechanobiological response profiles in layer-specific valve...

Area of Science:

• Biomaterials Science
• Cell Biology
• Mechanobiology

Background:

• Aortic valve homeostasis relies on valvular interstitial cells (VICs) within distinct leaflet layers.
• Pathological VIC differentiation to myofibroblasts drives disease, but layer-specific mechanobiological responses are unclear.
• Conventional culture methods struggle with primary VIC expansion and probing combined mechanobiological cues.

Purpose of the Study:

• To develop a microscale platform for assessing combined mechanobiological cues on VICs from different aortic valve layers.
• To investigate layer-specific mechanobiological response profiles of VICs.
• To understand how mechanical stimulation, matrix proteins, and soluble cues influence VIC behavior.

Main Methods:

• Developed a microfabricated composite material screening array for dynamic substrate stretch.
• Applied the array to study VICs isolated from distinct aortic valve leaflet layers.
• Assessed combined effects of substrate stretch, matrix proteins, and soluble cues on small cell populations.

Main Results:

• The screening array improved mechanical stability and cellular adhesion compared to conventional methods.
• VICs exhibited distinct mechanobiological profiles dependent on their leaflet layer of origin.
• Mechanical stimulation, matrix proteins, and soluble cues elicited integrated and distinct responses in layer-specific VICs.
• Myofibroblast differentiation was primarily dictated by cell origin, overriding potent cues like strain and TGF-β1.

Conclusions:

• Spatially distinct VIC subpopulations exhibit differential responses to microenvironmental cues.
• Cell origin is a critical factor in VIC mechanobiology and myofibroblast differentiation.
• The developed platform facilitates rapid identification of biological phenomena and has potential for drug screening and tissue engineering.