Design of a biaxial mechanobioreactor for engineering pediatric aortic 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 & Biomedical Engineering, University of Toronto; 3. Translational Biology & Engineering Program, University of Toronto
A major obstacle to producing ex-vivo tissue engineered heart valves (TEHVs) is the limited understanding of mechanical stimulation protocols necessary to produce functional constructs that mimic native valves. Functional biomimicry may be achieved in TEHVs by acquiring anisotropic mechanical properties and extracellular matrix (ECM) architecture similar to native tissues. Bioreactors have been designed to apply cyclic tensile strain in a planar biaxial configuration to cell-seeded substrates to induce ECM remodelling. Unfortunately, these devices are only designed to apply uniform biaxial strain to small specimens (< 25 mm x-25-mm) and cannot perform in vitro tissue mechanical property measurements. These designs are not optimized to uniformly strain larger TEHV constructs (~40 mm x 60 mm) and may lead to poorly controlled tissue remodelling across the tissue sheet. Further, the inability to monitor tissue properties prevents users from knowing when target properties are achieved or whether the strain protocol applied leads to desired tissue mechanical property changes. As such, we aim to design a novel bioreactor to stretch TEHV constructs biaxially and incorporate a novel photoacoustic elastography (PAE) technique to monitor construct mechanical properties in vitro.
Finite element analysis (FEA) was performed on an anisotropic tissue model to determine a specimen attachment configuration that maximizes the area of the cell-seeded scaffold subjected to uniform strain. The FEA models determined that a â€œ6-anchor-point/side trampolineâ€ setup produced a uniform strain region at least 18% larger than setups from existing bioreactors. Additionally, these models were used to evaluate strain patterns of different specimen shapes and sizes under biaxial stretch. The simulations showed the uniform strain region increased (from 43.6%-to-71.1%) when the side length parallel to the axis with a higher Youngâ€™s Modulus (E-=-16.6-MPa) was increased (20-mm to 60-mm). Conversely, the uniform strain area decreased (from 43.6%-to-4.5%) when the orthogonal side length (E-=-1.2-MPa) was increased by the same amount. This suggests specimen strain patterns are sensitive to the combination the constructâ€™s shape and material anisotropy when undergoing planar biaxial tensile strain.
To design and implement the â€œ6-anchor-point/ side trampolineâ€ setup, ANSYS was used to optimize component dimensions and for material selection. This process yielded two novel configurations that will be prototyped and evaluated by comparing generated specimen strain uniformity to the FEA data. PAE will be calibrated by scanning phantoms of known Youngâ€™s Modulus. The efficacy of PAE measurements for engineered tissues will be validated through comparisons with TEHV sheet mechanical property data obtained via biaxial testing. Finally, the bioreactor and PAE will be integrated together to monitor the evolution of the tissue mechanical properties and to trigger a stop protocol once targets are met.