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Inflammatory and Regenerative Processes in Bioresorbable Synthetic Pulmonary Valves Up to 2 Years in Sheep:  Spatiotemporal Insights Augmented by Raman Microspectroscopy

72 Pages Posted: 21 May 2021 Publication Status: Under Review

See all articles by Bente de Kort

Bente de Kort

Eindhoven University of Technology (TUE) - Department of Biomedical Engineering

J. Marzi

University of Tuebingen - Research Institute of Women's Health

E. Brauchle

University of Tuebingen - Research Institute of Women's Health

A.M. Lichauco

Eindhoven University of Technology (TUE) - Department of Biomedical Engineering

H.S. Bauer

Xeltis B.V.

A. Serrero

Xeltis B.V.

S. Dekker

Eindhoven University of Technology (TUE) - Department of Biomedical Engineering

M.A.J. Cox

Xeltis B.V.

F.J. Schoen

Harvard University - Harvard Medical School

Katja Schenke-Layland

University of Tübingen - NMI Natural and Medical Sciences Institute; Eberhard Karls University of Tübingen - Department of Women’s Health

C.V.C. Bouten

Eindhoven University of Technology (TUE) - Department of Biomedical Engineering; Eindhoven University of Technology (TUE) - Institute for Complex Molecular Systems (ICMS)

A.I.P.M. Smits

Eindhoven University of Technology (TUE) - Department of Biomedical Engineering; Eindhoven University of Technology (TUE) - Institute for Complex Molecular Systems (ICMS)

Abstract

In situ heart valve tissue engineering is an emerging approach in which resorbable, off-the-shelf available scaffolds are used to induce endogenous heart valve restoration. Such scaffolds are designed to recruit endogenous cells in vivo, which subsequently resorb polymer and produce and remodel new valvular tissue in situ. Recently, preclinical studies using electrospun supramolecular elastomeric valvular grafts have shown that this approach enables in situ regeneration of pulmonary valves with long-term functionality in vivo. However, the evolution and mechanisms of inflammation, polymer absorption and tissue regeneration are largely unknown, and adverse valve remodeling and intra- and inter-valvular variability have been reported. Therefore, the goal of the present study was to gain a mechanistic understanding of the in vivo regenerative processes by combining routine histology and immunohistochemistry, using a comprehensive sheep-specific antibody panel, with Raman microspectroscopy for the spatiotemporal analysis of in situ tissue-engineered pulmonary valves with follow-up to 24 months from a previous preclinical study in sheep. The analyses revealed a strong spatial heterogeneity in the influx of inflammatory cells, graft resorption, and foreign body giant cells. Collagen maturation occurred predominantly between 6 and 12 months after implantation, which was accompanied by a progressive switch to a more quiescent phenotype of infiltrating cells with properties of valvular interstitial cells. Variability among specimens in the extent of tissue remodeling was observed for follow-up times after 6 months. Taken together, these findings advance the understanding of key events and mechanisms in material-driven in situ heart valve tissue engineering.

Keywords: Tissue-engineered heart valve (TEHV), in situ tissue engineering, endogenous tissue restoration, biomaterial, foreign body response

Suggested Citation

de Kort, Bente and Marzi, J. and Brauchle, E. and Lichauco, A.M. and Bauer, H.S. and Serrero, A. and Dekker, S. and Cox, M.A.J. and Schoen, F.J. and Schenke-Layland, Katja and Bouten, C.V.C. and Smits, A.I.P.M., Inflammatory and Regenerative Processes in Bioresorbable Synthetic Pulmonary Valves Up to 2 Years in Sheep:  Spatiotemporal Insights Augmented by Raman Microspectroscopy. Available at SSRN: https://ssrn.com/abstract=3850523 or http://dx.doi.org/10.2139/ssrn.3850523

Bente De Kort (Contact Author)

Eindhoven University of Technology (TUE) - Department of Biomedical Engineering ( email )

PO Box 513
Eindhoven, 5600 MB
Netherlands

J. Marzi

University of Tuebingen - Research Institute of Women's Health ( email )

Wilhelmstr. 19
72074 Tuebingen, Baden Wuerttemberg 72074
Germany

E. Brauchle

University of Tuebingen - Research Institute of Women's Health ( email )

Wilhelmstr. 19
72074 Tuebingen, Baden Wuerttemberg 72074
Germany

A.M. Lichauco

Eindhoven University of Technology (TUE) - Department of Biomedical Engineering ( email )

PO Box 513
Eindhoven, 5600 MB
Netherlands

H.S. Bauer

Xeltis B.V. ( email )

Eindhoven
Netherlands

A. Serrero

Xeltis B.V. ( email )

Eindhoven
Netherlands

S. Dekker

Eindhoven University of Technology (TUE) - Department of Biomedical Engineering ( email )

PO Box 513
Eindhoven, 5600 MB
Netherlands

M.A.J. Cox

Xeltis B.V. ( email )

Eindhoven
Netherlands

F.J. Schoen

Harvard University - Harvard Medical School

25 Shattuck St
Boston, MA 02115
United States

Katja Schenke-Layland

University of Tübingen - NMI Natural and Medical Sciences Institute ( email )

Reutlingen
Germany

Eberhard Karls University of Tübingen - Department of Women’s Health ( email )

Germany

C.V.C. Bouten

Eindhoven University of Technology (TUE) - Department of Biomedical Engineering ( email )

PO Box 513
Eindhoven, 5600 MB
Netherlands

Eindhoven University of Technology (TUE) - Institute for Complex Molecular Systems (ICMS) ( email )

PO Box 513
Eindhoven, 5600 MB
Netherlands

A.I.P.M. Smits

Eindhoven University of Technology (TUE) - Department of Biomedical Engineering

PO Box 513
Eindhoven, 5600 MB
Netherlands

Eindhoven University of Technology (TUE) - Institute for Complex Molecular Systems (ICMS)

PO Box 513
Eindhoven, 5600 MB
Netherlands

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