Abstract

While there is a strong need to assess the safety and efficacy of novel therapies prior to evaluation in human patients, the ability to accurately model the complexities of coronary disease in-vitro and/or animal models is somewhat limited. Animal models, even those with genetic predispositions toward coronary disease do not exhibit high grade stenoses, similar to those that require treatment in human patients. At the same time, most in-vitro models and simulations of fluid-structure interactions cannot simultaneously capture the complex geometries, hemodynamics, and biomechanical response of human coronary disease. Here, we introduce a robust workflow to replicate an in-vitro platform incorporating compliant, realistic diseased coronary arteries in a flow loop under physiological conditions. Through ex-vivo imaging of cadaveric specimens, coupled with co-registered measurements of coronary biomechanics, we developed protocols that allow for fabrication and testing of highly realistic 3D printed models. The anatomical and biomechanical features of the coronary arteries, including local variations associated with the observed disease burdens were extracted and 3D printed, in high spatial resolution, using commercially available printers, making this methodology conveniently reproducible. Subsequently, the models were incorporated in a testing platform made of flow loops and valve resistance to mimic circulation and microvascular resistance respectively. Under physiological boundary conditions, we successfully collected measurements along the length of the vessels that exhibit a range of biomechanical characteristics from low to high values of modulus and assessed the impact of biomechanics on gold standard diagnostic and prognostic measures such as Fractional Flow Reserve. We demonstrated that incorporating the effects of local biomechanics significantly improves the predicted hemodynamics metrics with respect to ex-vivo coronaries.

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