Design of a Biaxial Mechanobioreactor for Engineering Pediatric Heart Valves

Wong, Edwin (1, 2, 3), Simmons, Craig (1, 2, 3)

(1) Department of Mechanical and Industrial Engineering, University of Toronto

(2) Institute of Biomaterials and Biomedical Engineering, University of Toronto

(3) Translational Biology and Engineering Program, Ted Rogers Center for Heart Research

Tissue engineering pediatric heart valves that biomimic the anisotropic biomechanical properties and function of healthy native valves remains a challenge. Mechanical stimulation of cells comprising these tissue engineered heart valves (TEHVs) is one attempted strategy to biomimic native valve extracellular matrix. Unfortunately, there is a limited understanding of in vitro mechanical stimulation protocols. Pressure-based bioreactors have been designed to apply cyclic biaxial tensile strain to TEHVs. Unfortunately, these devices use a single input to control bidirectional strain application which prevents directional strain modulation to tune the TEHV’s biomechanical properties. Another approach is to stretch each axis a tissue sheet individually, but existing devices are not optimized to uniformly strain TEHV constructs leading to uncontrolled tissue remodelling. As such, we aim to design and optimize a novel bioreactor to stretch TEHV constructs biaxially in a planar configuration.

Finite element models were created in ANSYS 14.0 to: i) design a novel configuration that maximizes biaxial strain uniformity on TEHV sheets; and ii) investigate strain patterns generated due to material and geometric anisotropy. A novel “capstan+cruciform” configuration was determined to improve and maximize strain uniformity by 39.5% over the trampoline setup, the gold standard in literature. To evaluate strain patterns, midpoint strains were measured for different side lengths (from 20 mm to 60 mm), side length ratios (1 ≤ LX/LY ≤ 3), Young’s moduli (1.2 MPa to 16 MPa) and material anisotropy (1 ≤ EX/EY ≤ 13.3). The directional midpoint strain ratios (εx/εy) were found to be coupled to the specimen’s EX/EY and LX/LY. Increasing the EX/EY led to a decrease in εx/εy (EX/EY = 1, εx/εy = 1; EX/EY = 13.3, εx/εy = 0.67). Conversely, increasing LX/LY increased εx/εy (LX/LY = 1, εx/εy = 1; LX/LY = 3, εx/εy = 48.9). Both the side length and Young’s modulus magnitudes had minimal effect on εx/εy. After, prototypes were built in-house.

We have designed a novel configuration that maximizes the applied biaxial strain uniformity for TEHVs inside a bioreactor. We demonstrated that strain magnitudes are coupled with the specimen’s material and geometric anisotropy. Since tissue constructs experience creep and material properties evolve throughout culture, these results emphasize the need for directional strain modulation to ensure consistency in the strain applied to the cells of TEHVs.