Transpecies heart valve transplant: Advanced studies of a bioengineered xeno-autograft

Background. Tissue engineering approaches utilizing biomechanically suitabl e cell-conductive matrixes should extend xenograft heart valve performance, durability, and growth potential to an extent presently attained only by t he pulmonary autograft. To test this hypothesis, we developed an acellular, unfixed porcine aortic valve-based construct. The performance of this valv e has been evaluated in vitro under simulated aortic conditions, as a pulmo nary valve replacement in sheep, and in aortic and pulmonary valve replacem ent 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 (AM L). After treatment to remove all histologically demonstrable leaflet cells and substantially reduce porcine cell-related immunoreactivity, three Valv e cusps were matched and sewn to form a symmetrical root utilizing the AML remnants as the inflow conduit. SynerGraft valves were evaluated by in vitr o hydrodynamics, and by in vivo implants in the right ventricular outflow t ract of weanling sheep for up to 336 days. Cryopreserved allograft valves s erved as control valves in both in vitro and in vivo evaluations. Valves we re also implanted as aortic valve replacements in humans. Results. In vitro pulsatile now testing, of the SynerGraft porcine valves d emonstrated 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 w ith no leaflet calcification over 150 days, and minimal deposition at 336 d ays. 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 implan ts demonstrates for the first time the possibility of an engineered autogra ft. (Ann Thorac Surg 2000;70:1962-9) (C) 2000 by The Society of Thoracic Su rgeons.