title: Improved Geometry of Decellularized Tissue Engineered Heart Valves to Prevent Leaflet Retraction.
abstract: Recent studies on decellularized tissue engineered heart valves (DTEHVs) showed rapid host cell repopulation and increased valvular insufficiency developing over time, associated with leaflet shortening. A possible explanation for this result was found using computational simulations, which revealed radial leaflet compression in the original valvular geometry when subjected to physiological pressure conditions. Therefore, an improved geometry was suggested to enable radial leaflet extension to counteract for host cell mediated retraction. In this study, we propose a solution to impose this new geometry by using a constraining bioreactor insert during culture. Human cell based DTEHVs (n = 5) were produced as such, resulting in an enlarged coaptation area and profound belly curvature. Extracellular matrix was homogeneously distributed, with circumferential collagen alignment in the coaptation region and global tissue anisotropy. Based on in vitro functionality experiments, these DTEHVs showed competent hydrodynamic functionality under physiological pulmonary conditions and were fatigue resistant, with stable functionality up to 16 weeks in vivo simulation. Based on implemented mechanical data, our computational models revealed a considerable decrease in radial tissue compression with the obtained geometrical adjustments. Therefore, these improved DTEHV are expected to be less prone to host cell mediated leaflet retraction and will remain competent after implantation.
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, Postbus 513, 5600 MB, Eindhoven, The Netherlands. b.sanders@tue.nl.|Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, The Netherlands. b.sanders@tue.nl.
authors.forename: Bart
authors.initials: B
authors.lastname: Sanders
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, Postbus 513, 5600 MB, Eindhoven, The Netherlands.|Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, The Netherlands.
authors.forename: Sandra
authors.initials: S
authors.lastname: Loerakker
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, Postbus 513, 5600 MB, Eindhoven, The Netherlands.
authors.forename: Emanuela S
authors.initials: ES
authors.lastname: Fioretta
authors.affiliation: Equipment & Prototype Center, Eindhoven University of Technology, Eindhoven, The Netherlands.
authors.forename: Dave J P
authors.initials: DJ
authors.lastname: Bax
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, Postbus 513, 5600 MB, Eindhoven, The Netherlands.|Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, The Netherlands.
authors.forename: Anita
authors.initials: A
authors.lastname: Driessen-Mol
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, Postbus 513, 5600 MB, Eindhoven, The Netherlands.|Swiss Center for Regenerative Medicine, University Hospital of Zürich, Zurich, Switzerland.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Hoerstrup
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, Postbus 513, 5600 MB, Eindhoven, The Netherlands.|Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, The Netherlands.
authors.forename: Frank P T
authors.initials: FP
authors.lastname: Baaijens
mesh_terms: D001696:Biomechanical Phenomena; D003094:Collagen; D006350:Heart Valve Prosthesis; D006351:Heart Valves / Q000502:physiology*; D006801:Humans; D023822:Tissue Engineering
chemical_list: D003094:Collagen
keywords: Bioreactor; Computational modeling; Decellularization; Heart valve replacement; Tissue engineering