Background: Tissue engineering approaches utilizing biomechanically suitable cell-conductive matrixes should extend xenograft heart valve performance, durability, and growth potential to an extent presently attained only by the pulmonary autograft. To test this hypothesis, we developed an acellular, unfixed porcine aortic valve-based construct. The performance of this valve has been evaluated in vitro under simulated aortic conditions, as a pulmonary valve replacement in sheep, and in aortic and pulmonary valve replacement in humans.
Methods: SynerGraft porcine heart valves (CryoLife Inc, Kennesaw, GA) were constructed from porcine noncoronary aortic valve cusp units consisting of aorta, noncoronary aortic leaflet, and attached anterior mitral leaflet (AML). After treatment to remove all histologically demonstrable leaflet cells and substantially reduce porcine cell-related immunoreactivity, three valve cusps were matched and sewn to form a symmetrical root utilizing the AML remnants as the inflow conduit. SynerGraft valves were evaluated by in vitro hydrodynamics, and by in vivo implants in the right ventricular outflow tract of weanling sheep for up to 336 days. Cryopreserved allograft valves served as control valves in both in vitro and in vivo evaluations. Valves were also implanted as aortic valve replacements in humans.
Results: In vitro pulsatile flow testing of the SynerGraft porcine valves demonstrated excellent valve function with large effective orifice areas and low gradients equivalent to a normal human aortic valve. Implants in sheep right ventricular outflow tracts showed stable leaflets with up to 80% of matrix recellularization with host fibroblasts and/or myofibroblasts, and with no leaflet calcification over 150 days, and minimal deposition at 336 days. Echocardiography studies showed normal hemodynamic performance during the implantation period. The human implants have proven functional for over 9 months.
Conclusions: A unique heart valve construct has been engineered to achieve the equivalent of an autograft. Short-term durability of these novel implants demonstrates for the first time the possibility of an engineered autograft.