Valentine Gesché

TexMi: development of tissue-engineered textile-reinforced mitral valve prosthesis.

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 patients anatomy and pathological situation by producing a patient-specific rapid prototyped mold.

Nondestructive monitoring of tissue-engineered constructs

Abstract Tissue engineering as a multidisciplinary field enables the development of living substitutes to replace, maintain, or restore diseased tissue and organs. Since the term was introduced in medicine in 1987, tissue engineering strategies have experienced significant progress. However, up to now, only a few substitutes were able to overcome the gap from bench to bedside and have been successfully approved for clinical use. Substantial donor variability makes it difficult to predict the quality of tissue-engineered constructs. It is essential to collect sufficient data to ensure that poor or immature constructs are not implanted into patients. The fulfillment of certain quality requirements, such as mechanical and structural properties, is crucial for a successful implantation. There is a clear need for new nondestructive and real-time online monitoring and evaluation methods for tissue-engineered constructs, which are applicable on the biomaterial, tissue, cellular, and subcellular levels. This paper reviews current established nondestructive techniques for implant monitoring including biochemical methods and noninvasive imaging.

Non-invasive Imaging of Tissue-Engineered Vascular Endothelium with Iron Oxide Nanoparticles

J. Frese, L. Hrdlicka, M. E. Mertens, L. Rongen, S. Koch, P. Schuster, V.N. Gesché, T. Lammers, P. Mela, F. Kiessling, S. Jockenhoevel Department of Tissue Engineering & Textile Implants, Institute of Applied Medical Engineering, RWTH Aachen University, Aachen, Germany, frese@hia.rwth-aachen.de Department of Experimental Molecular Imaging, RWTH-Aachen University, Aachen, Germany, Department of Tissue Engineering & Textile Implants, Institut für Textiltechnik, RWTH Aachen University, Aachen Germany

Artificial Textile Reinforced Tubular Aortic Heart Valves—Multi-scale Modelling and Experimental Validation

Tissue engineered valvular implants are in development as living and remodelling prostheses to replace damaged native valves. To improve the mechanical properties of the valve, textile is used as a reinforcing scaffold. To predict the behaviour and optimize the structure of such composites, it is necessary to understand the behaviour of the underlying components. The current study seeks to test a multi-scale approach often used in the field of composites to evaluate the behaviour of knitted textile reinforced elastomeric composites. The complex textile structure is divided into simplified models at different levels/structural units. Virtual experiments are conducted at each of these levels and their responses are fit to appropriate isotropic and anisotropic hyperelastic material models. The simulation responses obtained by conducting virtual experiments on the repeating unit cell (RUC) of the composite are then compared with experimental results, resulting in good agreement. After experimental validation, the multi-scale approach is used to predict the behaviour of artificial heart valves.

Combining material and structural elasticity - An approach to enhanced compliance of small-calibre vascular grafts

Up to date, commercially available vascular grafts for the replacement of diseased small calibre artery segments (d ≤ 6 mm) show low patency rates. One of the commonly named causes in literature is a low radial elasticity of the vascular graft, compared to that of the native vessel. At the Institut für Textiltechnik of RWTH Aachen University, a new approach combining elastic and non-elastic yarns in the warp knitting process is used for the production of vascular grafts. This unique combination of materialand structural elasticity is used to better model the compliance of native vessels and thus increase the patency rates of synthetic vascular grafts.The first section in your paper

Umbilical cord as human cell source for mitral valve tissue engineering - venous vs. arterial cells

Abstract Around 2% of the population in developed nations are affected by mitral valve disease and available valvular replacements are not designed for the atrioventricular position. Recently our group developed the first tissue-engineered heart valve (TEHV) specifically designed for the mitral position – the TexMi valve. The valve recapitulates the main components of the native valve, i.e. annulus, asymmetric leaflets and the crucial chordae tendineae. In the present study, we evaluated the human umbilical cord as a clinically applicable cell source for the TexMi valve. Valves produced with cells isolated from human umbilical cord veins (HUVs) and human umbilical cord arteries (HUAs) were conditioned for 21 days in custom-made bioreactors and evaluated in terms of extracellular matrix (ECM) composition and mechanical properties. In addition, static cell-laden fibrin discs were molded to investigate cell-mediated tissue contraction and differences in ECM production. HUA and HUV cells were able to deliver functional valves with a rich ECM composed mainly of collagen. Particularly noteworthy was the synthesis of elastin, which has been observed rarely in TEHV. The elastin synthesis was significantly higher in TexMi valves produced with HUV cells and therefore the HUV is considered to be the preferred cell source.