Engineered pulmonary artery tissues for measuring contractility, drug testing and disease modelling

Area of Science:

• Biomaterials science
• Vascular biology
• Drug discovery

Background:

• Pulmonary arterial hypertension (PAH) involves excessive pulmonary artery constriction, leading to right heart failure.
• Current laboratory models fail to accurately replicate human pulmonary artery vasoactivity.
• Improved models are crucial for developing effective PAH treatments.

Purpose of the Study:

• To develop a novel biomimetic platform for evaluating human pulmonary artery contractility.
• To create engineered pulmonary artery tissues (EPATs) for preclinical drug testing.
• To enhance the study of vascular smooth muscle cell (VSMC) behavior in health and disease.

Main Methods:

• Fabrication of 3D engineered pulmonary artery tissues (EPATs) using human pulmonary artery VSMCs in fibrin hydrogels.
• Suspension of VSMCs between silicone posts in a custom rack system within 24-well plates.
• Incorporation of endothelial cells to assess endothelium-dependent responses.

Main Results:

• EPATs demonstrated reproducible contractile and relaxant responses to various vasoactive agents and approved PAH drugs.
• Tissues from PAH patients showed heightened contractility and vasodilation.
• Endothelial cell incorporation allowed measurement of endothelium-dependent vasodilation.

Conclusions:

• EPATs are suitable for studying human arterial cell contractile behavior and preclinical drug screening.
• This novel biomimetic platform can significantly advance cardiovascular disease research.
• EPATs offer a promising tool for understanding and treating pulmonary arterial hypertension.