title: In situ heart valve tissue engineering using a bioresorbable elastomeric implant - From material design to 12 months follow-up in sheep.
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.
authors.affiliation: Department of Cardiothoracic Surgery, Academic Medical Center, Amsterdam, The Netherlands; Department of Cardiothoracic Surgery, University Medical Center, Utrecht, The Netherlands.
authors.forename: Jolanda
authors.initials: J
authors.lastname: Kluin
authors.affiliation: Department of Cardiothoracic Surgery, Academic Medical Center, Amsterdam, The Netherlands; Department of Cardiothoracic Surgery, University Medical Center, Utrecht, The Netherlands.
authors.forename: Hanna
authors.initials: H
authors.lastname: Talacua
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, The Netherlands; Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, The Netherlands.
authors.forename: Anthal I P M
authors.initials: AI
authors.lastname: Smits
authors.affiliation: 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.
authors.forename: Maximilian Y
authors.initials: MY
authors.lastname: Emmert
authors.affiliation: Xeltis BV, Eindhoven, The Netherlands.
authors.forename: Marieke C P
authors.initials: MC
authors.lastname: Brugmans
authors.affiliation: Institute for Regenerative Medicine (IREM), University of Zürich, Switzerland.
authors.forename: Emanuela S
authors.initials: ES
authors.lastname: Fioretta
authors.affiliation: Institute for Regenerative Medicine (IREM), University of Zürich, Switzerland.
authors.forename: Petra E
authors.initials: PE
authors.lastname: Dijkman
authors.affiliation: SyMO-Chem BV, Eindhoven, The Netherlands.
authors.forename: Serge H M
authors.initials: SH
authors.lastname: Söntjens
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, The Netherlands; Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, The Netherlands.
authors.forename: Renée
authors.initials: R
authors.lastname: Duijvelshoff
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, The Netherlands.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Dekker
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, The Netherlands.
authors.forename: Marloes W J T
authors.initials: MW
authors.lastname: Janssen-van den Broek
authors.affiliation: Institute for Regenerative Medicine (IREM), University of Zürich, Switzerland.
authors.forename: Valentina
authors.initials: V
authors.lastname: Lintas
authors.affiliation: Department of Pathology, University Medical Center, Utrecht, The Netherlands.
authors.forename: Aryan
authors.initials: A
authors.lastname: Vink
authors.affiliation: 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.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Hoerstrup
authors.affiliation: SyMO-Chem BV, Eindhoven, The Netherlands.
authors.forename: Henk M
authors.initials: HM
authors.lastname: Janssen
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, The Netherlands; Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, The Netherlands.
authors.forename: Patricia Y W
authors.initials: PY
authors.lastname: Dankers
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, The Netherlands; Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, The Netherlands.
authors.forename: Frank P T
authors.initials: FP
authors.lastname: Baaijens
authors.affiliation: 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.
authors.forename: Carlijn V C
authors.initials: CV
authors.lastname: Bouten
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D001705:Bioprosthesis; D020724:Elastomers / Q000737:chemistry*; D019544:Equipment Failure Analysis; D005260:Female; D006350:Heart Valve Prosthesis; D008422:Materials Testing; D011474:Prosthesis Design; D019919:Prosthesis Implantation; D011664:Pulmonary Valve / Q000254:growth & development* / Q000601:surgery*; D012756:Sheep; D016896:Treatment Outcome
chemical_list: D020724:Elastomers
keywords: Biodegradable polymers; Cardiovascular tissue engineering; Endogenous regeneration; Pulmonary valve replacement; Regenerative biomaterials; Supramolecular chemistry