Description
The use of left ventricular assist devices (LVADs) has improved the quality of life for patients with heart failure (HF). However, LVAD use alters the hemodynamics experienced by the aortic valve and therefore its biomechanics. High LVAD support especially increases the transvalvular pressure (TVP) across the aortic valve (AV). This causes the AV to remain closed for longer durations and is associated with the development of aortic insufficiency (AI). We hypothesize that increased mechanical strain experienced by the aortic valve induces cellular signaling that results in remodeling of the microenvironment and differentiation associated with fibrosis. To investigate this occurrence, a testbed for stretching valve interstitial cells (VICs) was developed. Two silicone materials, Sorta-Clear 18 and Sorta-Clear 40, were chosen to replicate the stress and strain experienced by the AV. Uniaxial testing of the SC40 and SC18 constructs exhibited moduli of 1.56 and 0.78 MPa, respectively, for a strain range of 0 to 0.05. Finite element analysis (FEA) simulations were modeled for each construct. Dynamic simulations of 0.005 m displacement validated the FEA models and the moduli results from uniaxial testing. The models were used to assess Strex system protocols, and the protocols compared to HeartMate II conditions. The model was modified with a collagen layer bonded to the membrane, and its material properties set to the those of the ventricularis and fibrosa layer of the native AV to analyze the stress and strain produced by the Strex protocols. The Strex STB-1400-4 system was used to impart cycling stretch to silicone constructs housing a collagen-cell matrix. The integrity of the collagen layer was tested by applying the Strex protocol with maximum stretch and frequency, while biocompatibility was examined through culture of cells and inspection of foreign body growth. VICs were encapsulated in a 3D collagen layer inside the wells of the constructs and cultured statically in vitro. Human embryonic kidney 293 (HEK) cells were prepared similarly and cyclically stretched at physiologically relevant conditions utilizing the stretching system. Immunostaining was conducted with both VICs and HEK cells for nuclear and F-actin presence, which confirmed viability throughout the testing procedures.
