Design and Mechanical Evaluation of a Physiological Mitral Valve Organ Culture System

Abstract

The physiological mechanical environment of the intact mitral valve is presumed to allow mechanotransductive, cell–cell and cell-extracellular matrix (ECM) signaling, which regulates cellular remodeling of the tissue ECM composition and structure. The goal of this work was to design an organ culture system to mimic the mechanical aspects of this environment, which in the future should allow for investigations to probe mitral valve biology and remodeling. This flow loop organ culture system uses an electronically pressure-controlled bladder pump to create a range of physiological pressure pulses in a ventricular chamber gated by inflow and outflow valves. The mitral valve attachment within the system is designed to maintain proper anatomical geometry and function. The entire system is filled with a culture medium and located within an environmental incubator to provide an appropriate environment for tissue viability. The system has been shown to accurately recreate a physiologic pressure waveform (up to 150 mmHg) and induce pulsatile flow (3 L/min), with a response time of 50 ms. In addition, the system can maintain sterility and has been used to culture mitral valves for up to 3 weeks. This system approximately recreates the physiological mechanical environment of a mitral valve. Future experiments will validate its ability to maintain the normal structure and composition of porcine mitral valves. After validation, this organ culture system can be used in longer term studies of heart valve responses to stimuli such as various biochemical agents or altered hemodynamics.