title: TexMi: development of tissue-engineered textile-reinforced mitral valve prosthesis.
abstract: Mitral valve regurgitation together with aortic stenosis is the most common valvular heart disease in Europe and North America. Mechanical and biological prostheses available for mitral valve replacement have significant limitations such as the need of a long-term anticoagulation therapy and failure by calcifications. Both types are unable to remodel, self-repair, and adapt to the changing hemodynamic conditions. Moreover, they are mostly designed for the aortic position and do not reproduce the native annular-ventricular continuity, resulting in suboptimal hemodynamics, limited durability, and gradually decreasing ventricular pumping efficiency. A tissue-engineered heart valve specifically designed for the mitral position has the potential to overcome the limitations of the commercially available substitutes. For this purpose, we developed the TexMi, a living textile-reinforced mitral valve, which recapitulates the key elements of the native one: annulus, asymmetric leaflets (anterior and posterior), and chordae tendineae to maintain the native annular-ventricular continuity. The tissue-engineered valve is based on a composite scaffold consisting of the fibrin gel as a cell carrier and a textile tubular structure with the twofold task of defining the gross three-dimensional (3D) geometry of the valve and conferring mechanical stability. The TexMi valves were molded with ovine umbilical vein cells and stimulated under dynamic conditions for 21 days in a custom-made bioreactor. Histological and immunohistological stainings showed remarkable tissue development with abundant aligned collagen fibers and elastin deposition. No cell-mediated tissue contraction occurred. This study presents the proof-of-principle for the realization of a tissue-engineered mitral valve with a simple and reliable injection molding process readily adaptable to the patient's anatomy and pathological situation by producing a patient-specific rapid prototyped mold.
authors.affiliation: 1 Department of Tissue Engineering and Textile Implants, Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University , Aachen, Germany .
authors.forename: Ricardo
authors.initials: R
authors.lastname: Moreira
authors.forename: Valentine N
authors.initials: VN
authors.lastname: Gesche
authors.forename: Luis G
authors.initials: LG
authors.lastname: Hurtado-Aguilar
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmitz-Rode
authors.forename: Julia
authors.initials: J
authors.lastname: Frese
authors.forename: Stefan
authors.initials: S
authors.lastname: Jockenhoevel
authors.forename: Petra
authors.initials: P
authors.lastname: Mela
mesh_terms: D000818:Animals; D019149:Bioreactors; D006350:Heart Valve Prosthesis; D006801:Humans; D006909:Hydroxyproline / Q000378:metabolism; D007150:Immunohistochemistry; D055595:Mechanical Phenomena; D008943:Mitral Valve / Q000502:physiology*; D012756:Sheep; D013784:Textiles; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D006909:Hydroxyproline