title: Multiple-Step Injection Molding for Fibrin-Based Tissue-Engineered Heart Valves.
abstract: Heart valves are elaborate and highly heterogeneous structures of the circulatory system. Despite the well accepted relationship between the structural and mechanical anisotropy and the optimal function of the valves, most approaches to create tissue-engineered heart valves (TEHVs) do not try to mimic this complexity and rely on one homogenous combination of cells and materials for the whole construct. The aim of this study was to establish an easy and versatile method to introduce spatial diversity into a heart valve fibrin scaffold. We developed a multiple-step injection molding process that enables the fabrication of TEHVs with heterogeneous composition (cell/scaffold material) of wall and leaflets without the need of gluing or suturing components together, with the leaflets firmly connected to the wall. The integrity of the valves and their functionality was proved by either opening/closing cycles in a bioreactor (proof of principle without cells) or with continuous stimulation over 2 weeks. We demonstrated the potential of the method by the two-step molding of the wall and the leaflets containing different cell lines. Immunohistology after stimulation confirmed tissue formation and demonstrated the localization of the different cell types. Furthermore, we showed the proof of principle fabrication of valves using different materials for wall (fibrin) and leaflets (hybrid gel of fibrin/elastin-like recombinamer) and with layered leaflets. The method is easy to implement, does not require special facilities, and can be reproduced in any tissue-engineering lab. While it has been demonstrated here with fibrin, it can easily be extended to other hydrogels.
authors: 1 Department of Tissue Engineering and Textile Implants, Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University , Aachen, Germany .
authors: Miriam
authors: M
authors: Weber
authors: 2 G.I.R. Bioforge, University of Valladolid , CIBER-BBN, Valladolid, Spain .
authors: Israel
authors: I
authors: Gonzalez de Torre
authors: 1 Department of Tissue Engineering and Textile Implants, Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University , Aachen, Germany .
authors: Ricardo
authors: R
authors: Moreira
authors: 1 Department of Tissue Engineering and Textile Implants, Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University , Aachen, Germany .
authors: Julia
authors: J
authors: Frese
authors: 1 Department of Tissue Engineering and Textile Implants, Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University , Aachen, Germany .
authors: Caroline
authors: C
authors: Oedekoven
authors: 2 G.I.R. Bioforge, University of Valladolid , CIBER-BBN, Valladolid, Spain .
authors: Matilde
authors: M
authors: Alonso
authors: 2 G.I.R. Bioforge, University of Valladolid , CIBER-BBN, Valladolid, Spain .
authors: Carlos J
authors: CJ
authors: Rodriguez Cabello
authors: 1 Department of Tissue Engineering and Textile Implants, Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University , Aachen, Germany .|3 Institut für Textiltecknik, RWTH Aachen University , Aachen, Germany .
authors: Stefan
authors: S
authors: Jockenhoevel
authors: 1 Department of Tissue Engineering and Textile Implants, Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University , Aachen, Germany .
authors: Petra
authors: P
authors: Mela
mesh_terms: D019149:Bioreactors; D005337:Fibrin / Q000737:chemistry*; D006351:Heart Valves; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D020100:Hydrogels; D005337:Fibrin
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