Willem Flameng1, Geofrey De Visscher2, Lindsay Mesure2, Hadewich Hermans2, Ramadan Jashari3, Bart Meuris2. 1. Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium. Electronic address: willem.flameng@med.kuleuven.be. 2. Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium. 3. European Homograft Bank, Brussels, Belgium.
Abstract
OBJECTIVE: This study assesses the performance and cellular features of decellularized ovine aortic homografts coated with stromal cell-derived factor-1α (SDF-1α) 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-1α-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-1α prevents cryopreserved heart valve-mediated immune response, conduit calcification, and pannus formation and stimulates re-endothelialization.
OBJECTIVE: This study assesses the performance and cellular features of decellularized ovine aortic homografts coated with stromal cell-derived factor-1α (SDF-1α) 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-1α-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-1α prevents cryopreserved heart valve-mediated immune response, conduit calcification, and pannus formation and stimulates re-endothelialization.
Authors: John D Vossler; Young Min Ju; J Koudy Williams; Steven Goldstein; James Hamlin; Sang Jin Lee; James J Yoo; Anthony Atala Journal: Biomed Mater Date: 2015-09-03 Impact factor: 3.715