The SynerGraft Valve: a New Acellular (nonglutaraldehyde-fixed) Tissue Heart Valve for Autologous Recellularization First Experimental Studies Before Clinical Implantation

The durability of current bioprosthetic heart valves is diminished by glutaraldehyde-associated leaflet calcification or by the associated absence of a cellular component capable of repair of wear-related damage. As a novel tissue engineering approach to improving replacement heart valve durability, we have developed a decellularization process to replace the use of cross-linking to limit xenograft antigenicity. The effectiveness of this process was assessed in a weanling sheep right ventricular outflow tract reconstruction model where valve function, calcification, and recellularization were examined. Porcine aortic valves were decellularized by a process designed to remove all histologically demonstrable leaflet cells. Stentless, bioprosthetic valves were fabricated from acellular tissues, cryopreserved, sterilized, and then implanted as pulmonary valve replacements in 4- to 6-month old female Suffolk sheep. Sheep aortic valves were implanted as allograft control subjects. After 150 days, the grafts were explanted and assessed histologically and by atomic absorption spectrophotometry for calcium content. All valves were hemodynamically functional at explant. Histological examination showed intact leaflets with in-growth of host fibroblastoid cells in all explanted porcine valves and no evidence of calcification. Porcine leaflet calcium content was unchanged over the duration of the implant (1.0+/-1.2 vs 1.5+/-1.8 mg/g dry weight, P = ns). Decellularization can stabilize xenogenic heart valves. Lack of calcification of acellular aortic leaflets suggests that prolonged durability of such valves is attainable without the use of cross-linking agents. The repopulation of the leaflet matrix offers additional promise of durability based on revitalization of the graft in vivo.