Reducing retraction in engineered tissues through design of sequential growth factor treatment

Area of Science:

• Biomedical Engineering
• Tissue Engineering
• Regenerative Medicine

Background:

• Heart valve disease affects millions globally, necessitating frequent valve replacements.
• Tissue engineered heart valves (TEHVs) offer a promising alternative to traditional valves but suffer from leaflet retraction.
• Predicting growth factor effects on engineered tissues is complex due to cell-ECM interactions.

Purpose of the Study:

• To investigate sequential fibroblast growth factor 2 (FGF-2) and transforming growth factor beta 1 (TGF-β1) treatments to reduce TEHV retraction.
• To understand how these growth factors influence cell contractile forces and extracellular matrix (ECM) stiffness.
• To develop a mathematical model for predicting growth factor treatment outcomes.

Main Methods:

• Utilized a custom 3D tissue construct culturing and monitoring system.
• Applied sequential FGF-2 and TGF-β1 treatments to engineered heart valve tissues.
• Measured tissue retraction, cell contractile forces, and ECM elastic modulus.
• Developed and verified a mathematical model for growth factor treatment dynamics.

Main Results:

• Achieved an 85% reduction in tissue retraction compared to controls.
• Increased ECM elastic modulus by 260% without significantly increasing contractile forces.
• Developed a validated mathematical model predicting growth factor treatment effects.

Conclusions:

• Sequential FGF-2 and TGF-β1 treatments effectively minimize TEHV retraction by modulating cell-ECM biomechanics.
• Mathematical modeling provides a tool for optimizing growth factor therapies for TEHVs and other fibrotic diseases.
• Findings advance the design of next-generation TEHVs with improved durability and reduced retraction.