title: Is Transcatheter Aortic Valve Implantation of Living Tissue-Engineered Valves Feasible? An In Vitro Evaluation Utilizing a Decellularized and Reseeded Biohybrid Valve.
abstract: Transcatheter aortic valve implantation (TAVI) is a fast-growing, exciting field of invasive therapy. During the last years many innovations significantly improved this technique. However, the prostheses are still associated with drawbacks. The aim of this study was to create cell-seeded biohybrid aortic valves (BAVs) as an ideal implant by combination of assets of biological and artificial materials. Furthermore, the influence of TAVI procedure on tissue-engineered BAV was investigated. BAV (n=6) were designed with decellularized homograft cusps and polyurethane walls. They were seeded with fibroblasts and endothelial cells isolated from saphenous veins. Consecutively, BAV were conditioned under low pulsatile flow (500 mL/min) for 5 days in a specialized bioreactor. After conditioning, TAVI-simulation was performed. The procedure was concluded with re-perfusion of the BAV for 2 days at an increased pulsatile flow (1100 mL/min). Functionality was assessed by video-documentation. Samples were taken after each processing step and evaluated by scanning electron microscopy (SEM), immunohistochemical staining (IHC), and Live/Dead-assays. The designed BAV were fully functioning and displayed physiologic behavior. After cell seeding, static cultivation and first conditioning, confluent cell layers were observed in SEM. Additionally, IHC indicated the presence of endothelial cells and fibroblasts. A significant construction of extracellular matrix was detected after the conditioning phase. However, a large number of lethal cells were observed after crimping by Live/Dead staining. Analysis revealed that the cells while still being present directly after crimping were removed in subsequent perfusion. Extensive regions of damaged cell-layers were detected by SEM-analysis substantiating these findings. Furthermore, increased ICAM expression was detected after re-perfusion as manifestation of inflammatory reaction. The approach to generate biohybrid valves is promising. However, damages inflicted during the crimping process seem not to be immediately detectable. Due to severe impacts on seeded cells, the strategy of living TE valves for TAVI should be reconsidered.
authors.affiliation: Department of Cardiac Surgery, Laboratory for Tissue Engineering, Grosshadern Medical Centre, Ludwig Maximilians University, Munich.|Department of Medical Engineering, Technical University Munich, Garching, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Koenig
authors.affiliation: Department of Cardiac Surgery, Laboratory for Tissue Engineering, Grosshadern Medical Centre, Ludwig Maximilians University, Munich.
authors.forename: Jang-Sun
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Cardiac Surgery, Laboratory for Tissue Engineering, Grosshadern Medical Centre, Ludwig Maximilians University, Munich.
authors.forename: Bassil
authors.initials: B
authors.lastname: Akra
authors.affiliation: Department of Cardiac Surgery, Laboratory for Tissue Engineering, Grosshadern Medical Centre, Ludwig Maximilians University, Munich.
authors.forename: Trixi
authors.initials: T
authors.lastname: Hollweck
authors.affiliation: Department of Medical Engineering, Technical University Munich, Garching, Germany.
authors.forename: Erich
authors.initials: E
authors.lastname: Wintermantel
authors.affiliation: Department of Cardiac Surgery, Laboratory for Tissue Engineering, Grosshadern Medical Centre, Ludwig Maximilians University, Munich.
authors.forename: Christian
authors.initials: C
authors.lastname: Hagl
authors.affiliation: Department of Cardiac Surgery, Laboratory for Tissue Engineering, Grosshadern Medical Centre, Ludwig Maximilians University, Munich.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Thierfelder
mesh_terms: D001021:Aortic Valve / Q000166:cytology / Q000601:surgery*; D001705:Bioprosthesis; D019149:Bioreactors; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology; D004867:Equipment Design; D005347:Fibroblasts / Q000166:cytology; D006350:Heart Valve Prosthesis; D006801:Humans; D011140:Polyurethanes / Q000737:chemistry; D012501:Saphenous Vein / Q000166:cytology; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry; D065467:Transcatheter Aortic Valve Replacement
chemical_list: D011140:Polyurethanes
keywords: Cardiovascular tissue engineering-Aortic valve-Decellularization-Transcatheter aortic valve implantation-Homografts-Bioreactor