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Biomaterials. 2017 May;125:101-117. doi: 10.1016/j.biomaterials.2017.02.007. Epub 2017 Feb 8.

In situ heart valve tissue engineering using a bioresorbable elastomeric implant - From material design to 12 months follow-up in sheep.

Author information

1
Department of Cardiothoracic Surgery, Academic Medical Center, Amsterdam, The Netherlands; Department of Cardiothoracic Surgery, University Medical Center, Utrecht, The Netherlands.
2
Department of Biomedical Engineering, Eindhoven University of Technology, The Netherlands; Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, The Netherlands.
3
Institute for Regenerative Medicine (IREM), University of Zürich, Switzerland; Heart Center Zürich, University Hospital Zürich, Switzerland; Wyss Translational Center Zürich, ETH and University of Zürich, Switzerland.
4
Xeltis BV, Eindhoven, The Netherlands.
5
Institute for Regenerative Medicine (IREM), University of Zürich, Switzerland.
6
SyMO-Chem BV, Eindhoven, The Netherlands.
7
Department of Biomedical Engineering, Eindhoven University of Technology, The Netherlands.
8
Department of Pathology, University Medical Center, Utrecht, The Netherlands.
9
Department of Biomedical Engineering, Eindhoven University of Technology, The Netherlands; Institute for Regenerative Medicine (IREM), University of Zürich, Switzerland; Wyss Translational Center Zürich, ETH and University of Zürich, Switzerland.
10
Department of Biomedical Engineering, Eindhoven University of Technology, The Netherlands; Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, The Netherlands. Electronic address: c.v.c.bouten@tue.nl.

Abstract

The creation of a living heart valve is a much-wanted alternative for current valve prostheses that suffer from limited durability and thromboembolic complications. Current strategies to create such valves, however, require the use of cells for in vitro culture, or decellularized human- or animal-derived donor tissue for in situ engineering. Here, we propose and demonstrate proof-of-concept of in situ heart valve tissue engineering using a synthetic approach, in which a cell-free, slow degrading elastomeric valvular implant is populated by endogenous cells to form new valvular tissue inside the heart. We designed a fibrous valvular scaffold, fabricated from a novel supramolecular elastomer, that enables endogenous cells to enter and produce matrix. Orthotopic implantations as pulmonary valve in sheep demonstrated sustained functionality up to 12 months, while the implant was gradually replaced by a layered collagen and elastic matrix in pace with cell-driven polymer resorption. Our results offer new perspectives for endogenous heart valve replacement starting from a readily-available synthetic graft that is compatible with surgical and transcatheter implantation procedures.

KEYWORDS:

Biodegradable polymers; Cardiovascular tissue engineering; Endogenous regeneration; Pulmonary valve replacement; Regenerative biomaterials; Supramolecular chemistry

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