Coating with fibronectin and stromal cell-derived factor-18α of decellularized homografts used for right ventricular outflow tract reconstruction eliminates immune response-related degeneration

Objective: This study assesses the performance and cellular features of decellularized ovine aortic homografts coated with stromal cell-derived factor-1a (SDF-1 alpha) and its natural linker, fibronectin (FN), after implantation in the right ventricular outflow tract of adolescent sheep. Methods: Right ventricular outflow tract reconstructions using cryopreserved (n=7), decellularized (n=8), and decellularized FN/SDF-1 alpha- coated aortic ovine homografts (n=6) were performed. Echocardiographic, morphologic, radiographic, histologic, and immunohistochemical examinations were performed 5 months after implantation. Results: There were no hemodynamic differences between groups, except for the decellularized homografts' tendency to develop more valve regurgitation (3 of 8 grafts had regurgitation> 2/4). All decellularized, but coated, grafts had normal hemodynamics. Decellularized valve conduits were less calcified than cryopreserved conduits (P<. 05), but coated valve conduits were free of calcification (P<. 05). The same was found for pannus in the outflow parts. Immune response (CD45(+), CD45R(+), or CD11b(+) cells) was decreased in decellularized valves compared with cryopreserved grafts, but was virtually absent (P <. 05) in coated grafts. Collagen organization and density in the leaflets and walls were decreased in cryopreserved and decellularized valves, but not in coated valves (P<. 05). Coating improved re-endothelialization (P<. 05). Conclusions: Coating of decellularized allografts with FN/SDF-1 alpha prevents cryopreserved heart valvemediated immune response, conduit calcification, and pannus formation and stimulates re-endothelialization.