title: Engineering of a bio-functionalized hybrid off-the-shelf heart valve.
abstract: Currently available heart valve replacements are limited in long-term performance or fail due to leaflet thickening, lack of growth or remodeling potential. In order to address these issues, it is necessary to mimic multiple factors of the native valvular extracellular matrix (ECM) such as architecture, mechanical behavior and biochemical signals. Here, we successfully generated an electrospun PEGdma-PLA scaffold adapted to the structure and mechanical properties of native valve leaflets. Valvular interstitial cells (VICs) and valvular endothelial cells (VECs) were seeded on the scaffold and when cultured under physiological conditions in a bioreactor, the construct performed like a native leaflet. Atomic force microscopy (AFM) was employed to obtain detailed mechanical information from the leaflets, which enabled the first layer-specific measurement of the Young's modulus. Interestingly, spongiosa stiffness was much lower compared to the fibrosa and ventricularis. Moreover, investigations into human fetal heart valve development identified collagen type I and versican as important structural proteins. As a proof of principle, these proteins were introduced to the scaffold, demonstrating the ability to bio-functionalize the hybrid valve based on natures' blueprint.
authors: University Women's Hospital, Eberhard-Karls-University Tübingen, 72076 Tübingen, Germany; Dept. of Cell and Tissue Engineering, Fraunhofer Institute for Interfacial Engineering and Biotechnology (IGB), 70569 Stuttgart, Germany; Institute for Interfacial Process Engineering and Plasma Technology (IGVP), University of Stuttgart, 70569 Stuttgart, Germany.
authors: Svenja
authors: S
authors: Hinderer
authors: Institute of Applied Physics and LISA+, Eberhard-Karls-University Tübingen, 72076 Tübingen, Germany.
authors: Jan
authors: J
authors: Seifert
authors: University Women's Hospital, Eberhard-Karls-University Tübingen, 72076 Tübingen, Germany.
authors: Miriam
authors: M
authors: Votteler
authors: Dept. of Cell and Tissue Engineering, Fraunhofer Institute for Interfacial Engineering and Biotechnology (IGB), 70569 Stuttgart, Germany.
authors: Nian
authors: N
authors: Shen
authors: Institute of Applied Physics and LISA+, Eberhard-Karls-University Tübingen, 72076 Tübingen, Germany.
authors: Johannes
authors: J
authors: Rheinlaender
authors: Institute of Applied Physics and LISA+, Eberhard-Karls-University Tübingen, 72076 Tübingen, Germany.
authors: Tilman E
authors: TE
authors: Schäffer
authors: University Women's Hospital, Eberhard-Karls-University Tübingen, 72076 Tübingen, Germany; Dept. of Cell and Tissue Engineering, Fraunhofer Institute for Interfacial Engineering and Biotechnology (IGB), 70569 Stuttgart, Germany; Dept. of Medicine/Cardiology, Cardiovascular Research Laboratories, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. Electronic address: katja.schenke-layland@igb.fraunhofer.de.
authors: Katja
authors: K
authors: Schenke-Layland
mesh_terms: D000818:Animals; D006350:Heart Valve Prosthesis; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D013552:Swine; D023822:Tissue Engineering; D054457:Tissue Scaffolds
keywords: Cardiac tissue engineering; ECM (extracellular matrix); Mechanical properties; Nanotopography; Non-woven fabric