Quantifying heart valve interstitial cell contractile state using highly tunable poly(ethylene glycol) hydrogels.

Area of Science:

• Biomaterials Science
• Cell Biology
• Biomedical Engineering

Background:

• Valve interstitial cells (VICs) are crucial in heart valve structure and pathology.
• VIC activation leads to extracellular matrix (ECM) remodeling and increased contractility, indicated by α-smooth muscle actin (αSMA).
• Traditional 2D studies do not accurately represent the 3D mechanical environment of native valve tissue.

Purpose of the Study:

• To investigate the active contractile behavior of aortic VICs (AVICs) within a 3D hydrogel environment.
• To assess how microenvironmental factors, such as gel stiffness and adhesion site availability, influence AVIC contractility.
• To develop a tunable 3D system for studying VIC biomechanics.

Main Methods:

• AVICs were encapsulated in poly(ethylene glycol) (PEG) hydrogels.
• Flexural-deformation tests were performed to measure the effective shear modulus (μ) of the constructs.
• A finite element model was used to analyze the experimental data.
• AVIC volume changes were monitored via direct imaging within the hydrogels.

Main Results:

• AVIC active contraction increased the effective shear modulus (μ) of the PEG hydrogels.
• This effect was more pronounced in softer gels and dependent on the concentration of CRGDS adhesion sites.
• AVICs exhibited a time-dependent decrease in volume when induced into a hypertensive state.
• AVIC contraction was regulated by both intrinsic gel stiffness and CRGDS peptide concentrations.

Conclusions:

• VIC contractile state can be modulated by the 3D microenvironment using tunable PEG hydrogels.
• This 3D micromechanical model provides a platform for studying VICs in a more physiologically relevant context.
• The approach has potential for differentiating normal and diseased VIC biomechanical properties.