BS20 Engineered pulmonary artery tissues – a novel technique to assess vascular contractility

Introduction Conventional monolayer culture of vascular smooth muscle cells suppresses their contractility, a property crucial to cardiovascular function and disease. Therefore, we developed a new model of three-dimensional bioengineered arteries using hydrogels containing human pulmonary artery smooth muscle cells, which exhibit physiologically relevant vasoactivity in vitro. These miniaturised constructs are known as 'Engineered Pulmonary Artery Tissues' (EPATs). Methods EPATs were produced using custom-made racks fabricated from polydimethylsiloxane (PDMS) using a 3D-printed resin mould. Primary human pulmonary artery smooth muscle cells were suspended with fibrinogen and seeded between pairs of posts hanging from the PDMS racks. 3D constructs were formed after rapid fibrin polymerisation by thrombin and auxotonic stretch exerted by the PDMS posts was designed to re-establish contractility within smooth muscle cells. Results EPATs accurately reproduce vasoconstriction and vasodilation, measured by changes in EPAT length captured using light microscopy. Contractility is robust and reproducible and EPATs are viable for over 3 weeks enabling both long-term treatments and repeated measurements over time. Concentration-response curves were generated in EPATs for a range of vasoconstrictors (KCl, endothelin-1, U46619) and vasodilators (bosentan, prostacyclin, selexipag). Importantly, in EPATs these drugs exhibited pharmacological profiles highly similar to those seen in human pulmonary arteries. Conclusions The EPATs technique provides the unique ability to measure smooth muscle cell contractility in vitro and has enormous potential to address the clinical need for better vasodilatory therapies for diseases such as pulmonary arterial hypertension. Conflict of Interest None