| Autor: |
Motta SE; Institute for Regenerative Medicine (IREM), University of Zurich, Wagistrasse 12, 8952, Schlieren, Switzerland.; Wyss Translational Center Zurich, University and ETH Zurich, Zurich, Switzerland., Fioretta ES; Institute for Regenerative Medicine (IREM), University of Zurich, Wagistrasse 12, 8952, Schlieren, Switzerland., Lintas V; Wyss Translational Center Zurich, University and ETH Zurich, Zurich, Switzerland., Dijkman PE; Institute for Regenerative Medicine (IREM), University of Zurich, Wagistrasse 12, 8952, Schlieren, Switzerland., Hilbe M; Institute of Veterinary Pathology, University of Zurich, Zurich, Switzerland., Frese L; Institute for Regenerative Medicine (IREM), University of Zurich, Wagistrasse 12, 8952, Schlieren, Switzerland., Cesarovic N; Department of Cardiothoracic and Vascular Surgery, German Heart Center Berlin, Berlin, Germany.; Department of Health Sciences and Technology, Swiss Federal Institute of Technology, Zurich, Switzerland., Loerakker S; Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.; Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, The Netherlands., Baaijens FPT; Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands., Falk V; Department of Cardiothoracic and Vascular Surgery, German Heart Center Berlin, Berlin, Germany.; Department of Health Sciences and Technology, Swiss Federal Institute of Technology, Zurich, Switzerland.; Department of Cardiovascular Surgery, Charité Universitätsmedizin Berlin, Berlin, Germany., Hoerstrup SP; Institute for Regenerative Medicine (IREM), University of Zurich, Wagistrasse 12, 8952, Schlieren, Switzerland.; Wyss Translational Center Zurich, University and ETH Zurich, Zurich, Switzerland., Emmert MY; Institute for Regenerative Medicine (IREM), University of Zurich, Wagistrasse 12, 8952, Schlieren, Switzerland. maximilian.emmert@irem.uzh.ch.; Wyss Translational Center Zurich, University and ETH Zurich, Zurich, Switzerland. maximilian.emmert@irem.uzh.ch.; Department of Cardiothoracic and Vascular Surgery, German Heart Center Berlin, Berlin, Germany. maximilian.emmert@irem.uzh.ch.; Department of Cardiovascular Surgery, Charité Universitätsmedizin Berlin, Berlin, Germany. maximilian.emmert@irem.uzh.ch. |
| Abstrakt: |
Regenerative tissue-engineered matrix-based heart valves (TEM-based TEHVs) may become an alternative to currently-used bioprostheses for transcatheter valve replacement. We recently identified TEM-based TEHVs-geometry as one key-factor guiding their remodeling towards successful long-term performance or failure. While our first-generation TEHVs, with a simple, non-physiological valve-geometry, failed over time due to leaflet-wall fusion phenomena, our second-generation TEHVs, with a computational modeling-inspired design, showed native-like remodeling resulting in long-term performance. However, a thorough understanding on how TEHV-geometry impacts the underlying host cell response, which in return determines tissue remodeling, is not yet fully understood. To assess that, we here present a comparative samples evaluation derived from our first- and second-generation TEHVs. We performed an in-depth qualitative and quantitative (immuno-)histological analysis focusing on key-players of the inflammatory and remodeling cascades (M1/M2 macrophages, α-SMA + - and endothelial cells). First-generation TEHVs were prone to chronic inflammation, showing a high presence of macrophages and α-SMA + -cells, hinge-area thickening, and delayed endothelialization. Second-generation TEHVs presented with negligible amounts of macrophages and α-SMA + -cells, absence of hinge-area thickening, and early endothelialization. Our results suggest that TEHV-geometry can significantly influence the host cell response by determining the infiltration and presence of macrophages and α-SMA + -cells, which play a crucial role in orchestrating TEHV remodeling. |
