Development of a Biaxial Stretch Bioreactor and Finite Element Models for Mechanobiological Study of Aortic Valve Leaflets

Aortic heart valve disease is a significant cause of mortality worldwide; and replacement surgery is necessary in 70% of cases. Tissue engineered heart valves (TEHVs) are biocompatible and biodegradable, with ability to grow with the patient. However, to date, TEHVs mostly lack ability to withstand native mechanical forces since they are unable to mimic the heterogeneous and anisotropic structure of extracellular matrix (ECM) in native valves. Cyclic stretch is known to modulate ECM fiber synthesis and alignment. However, little tools are available for studying the interaction between aortic tissues and stretch condition. Finite element method is a powerful tool to simulate the complex structure of aortic valve, however, most current simulations modeled the leaflet as a homogenous material, and none of them took the distinctions between two surface layers into account, which were critical for the proper function of the aortic valve.To study the effects of cyclic stretch on extracellular matrix remodeling, the heterogeneous properties of the aortic leaflet, and the effects of heterogeneity on the function of valve, we have 1) Designed, fabricated and validated a biaxial stretch bioreactor; 2) Analyzed train patterns of native aortic leaflets using digital image correlation method; 3) Designed and validated an anisotropic and heterogeneous finite element (FE) model for leaflets. These studies provided insights into the interaction between aortic valve tissue and the mechanical environment, anisotropy and heterogeneity of aortic leaflets ECM due to the distribution of collagen fibers, and detailed distinct strain patterns in fibrosa vs. ventricularis sides and 3 aortic leaflets. Our novel biaxial stretch bioreactor and refined FE model of aortic leaflet will pave path for other scientists to study mechanobiology, design and condition engineered tissues and simulate engineered aortic valve grafts or pathology of calcium deposition.