oa Functional Performance and Biomechanics of Decellularized Human Aortic Valves

Allograft decellularization based on detergents and/or enzymes to reduce antigenicity has been reported to damage tissue structure. We applied to human aortic valves a non-detergent/non-protease decellularization treatment prior to cryopreservation. To ensure that the method did not negatively impact valve structure, we submitted decellularized and conventional human aortic valves to pulsatile flow characterizations and accelerated wear testing (to 80 million cycles) under both normal and elevated aortic valve flow conditions. The biomechanical properties of decellularized aortic valve tissues were compared to those of non-decellularized aortic valves. Valve performance was assessed using six conventional and six decellularized human aortic valves (internal valve diameter of 21mm±1mm). Valves were placed in accelerated wear testers, at a cycle rate of 200beats/min as specified in ISO 5840. All valves underwent pulsatile flow characterization before testing and at 20 million cycle intervals up to 80 million loading cycles (pressure>100mmHg). Images captured during pulsatile testing at peak systole and diastole were used to evaluate proper valve function, full leaflet coaptation and wear related damage. Tissue biomechanics was evaluated pair-wise using ten bisected valves, half conventionally treated, half decellularized. For each, conduit and leaflet circumferential ultimate tensile strength (UTS), and conduit and myocardium suture retention strength were evaluated. Compared to conventional human aortic heart valves, the decellularized valves showed comparable valve performance based on effective orifice area before accelerated testing (1.57±0.3 vs 1.51±0.2 cm2, decellularized and conventional, respectively) and similar non-significant decrease after reaching an accumulated 80 million cycles (1.40±0.2 vs. 1.45±0.3 cm2). Both populations met the minimum performance requirements specified in ISO 5840 for effective orifice area and regurgitant fraction. There was no significant increase in retrograde flow due to post-wear leakage. Biomechanical testing demonstrated leaflet and conduit circumferential UTS and conduit and myocardium suture retention strength of decellularized valves were equal to or greater than the conventional valves. From these measurements we conclude that there is no quantifiable impact on valve functionality, performance or biomechanics due to the SynerGraft® (non-detergent based) decellularization process.