Spatially controlling cardiac fibroblast-to-myofibroblast transition using Young's modulus patterned GelMA hydrogels

Area of Science:

• Biomaterials Science
• Mechanobiology
• Tissue Engineering

Background:

• Mechanical cues are critical regulators of tissue development and disease.
• Existing in vitro systems struggle to replicate complex mechanical environments.
• Fibroblast behavior, including migration and differentiation, is significantly influenced by mechanical stimuli.

Purpose of the Study:

• To develop a photolithographic platform for precise spatial patterning of Young's modulus in gelatin methacryol (GelMA) hydrogels.
• To investigate the impact of spatially controlled mechanical cues on fibroblast behavior, specifically the fibroblast-to-myofibroblast transition and durotaxis.
• To create physiologically relevant mechanical gradients for studying mechanobiology.

Main Methods:

• Utilized a ruthenium/sodium persulfate (SPS) photoinitiation system for photolithography.
• Achieved tunable Young's modulus in GelMA hydrogels (4-46 kPa) by controlling light intensity.
• Generated binary and linear Young's modulus patterns and gradients with high spatial resolution (~20 μm).

Main Results:

• Demonstrated successful spatial patterning of Young's modulus, creating transitions from 10 kPa to 45 kPa.
• Confirmed that increased Young's modulus drives fibroblast-to-myofibroblast transition, evidenced by increased cell volume and α-smooth muscle actin (α-SMA) expression.
• Observed fibroblasts exhibiting durotaxis, migrating towards stiffer regions, and aligning with mechanical gradients.

Conclusions:

• The developed photopatterning platform offers precise control over material mechanics, mimicking native tissue heterogeneity.
• This system provides a powerful tool for studying mechanobiological responses, including cardiac fibrosis and scar formation.
• The platform's versatility supports diverse applications in mechanobiology and regenerative medicine.