Geometry influences inflammatory host cell response and remodeling in tissue-engineered heart valves in-vivo

Sarah E. Motta, Emanuela S. Fioretta, Valentina Lintas, Petra E. Dijkman, Monika Hilbe, Laura Frese, Nikola Cesarovic, Sandra Loerakker, Frank P.T. Baaijens, Volkmar Falk, Simon P. Hoerstrup, Maximilian Y. Emmert (Corresponding author)

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Samenvatting

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.

Originele taal-2Engels
Artikelnummer19882
Aantal pagina's14
TijdschriftScientific Reports
Volume10
Nummer van het tijdschrift1
DOI's
StatusGepubliceerd - 16 nov. 2020

Financiering

The authors gratefully acknowledge the funding from the European Union’s Seventh Framework Program (FP7/2007-2013) under grant agreement n° 242008. S.E.M. was supported by the University of Zurich Forschnug-skredit (FK-14-031). E.S.F. was partly funded through the Swiss National Science Foundation (PZ00P3_180138). M.Y.E. and S.L. have received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme, grant agreement no. 852814 (TAVI4Life) and grant agreement no. 802967 (MechanoSignaling). We are thankful to Flurin Arner for supporting and contributing to this work.

FinanciersFinanciernummer
European Union’s Horizon Europe research and innovation programme
University of ZurichFK-14-031
European Union’s Horizon Europe research and innovation programme852814, 802967, 242008
European Research Council
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungPZ00P3_180138

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