title: Transcatheter implantation of homologous "off-the-shelf" tissue-engineered heart valves with self-repair capacity: long-term functionality and rapid in vivo remodeling in sheep.
abstract: OBJECTIVE
  This study sought to evaluate long-term in vivo functionality, host cell repopulation, and remodeling of "off-the-shelf" tissue engineered transcatheter homologous heart valves.
  
  
  BACKGROUND
  Transcatheter valve implantation has emerged as a valid alternative to conventional surgery, in particular for elderly high-risk patients. However, currently used bioprosthetic transcatheter valves are prone to progressive dysfunctional degeneration, limiting their use in younger patients. To overcome these limitations, the concept of tissue engineered heart valves with self-repair capacity has been introduced as next-generation technology.
  
  
  METHODS
  In vivo functionality, host cell repopulation, and matrix remodeling of homologous transcatheter tissue-engineered heart valves (TEHVs) was evaluated up to 24 weeks as pulmonary valve replacements (transapical access) in sheep (n = 12). As a control, tissue composition and structure were analyzed in identical not implanted TEHVs (n = 5).
  
  
  RESULTS
  Transcatheter implantation was successful in all animals. Valve functionality was excellent displaying sufficient leaflet motion and coaptation with only minor paravalvular leakage in some animals. Mild central regurgitation was detected after 8 weeks, increasing to moderate after 24 weeks, correlating to a compromised leaflet coaptation. Mean and peak transvalvular pressure gradients were 4.4 ± 1.6 mm Hg and 9.7 ± 3.0 mm Hg, respectively. Significant matrix remodeling was observed in the entire valve and corresponded with the rate of host cell repopulation.
  
  
  CONCLUSIONS
  For the first time, the feasibility and long-term functionality of transcatheter-based homologous off-the-shelf tissue engineered heart valves are demonstrated in a relevant pre-clinical model. Such engineered heart valves may represent an interesting alternative to current prostheses because of their rapid cellular repopulation, tissue remodeling, and therewith self-repair capacity. The concept of homologous off-the-shelf tissue engineered heart valves may therefore substantially simplify previous tissue engineering concepts toward clinical translation.
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.
authors.forename: Anita
authors.initials: A
authors.lastname: Driessen-Mol
authors.affiliation: Swiss Center of Regenerative Medicine, University and University Hospital Zürich, Zürich, Switzerland; Center Surgery, Division of Surgical Research, University Hospital Zürich, Zürich, Switzerland; Heart Center Zürich, University Hospital Zürich, Zürich, Switzerland.
authors.forename: Maximilian Y
authors.initials: MY
authors.lastname: Emmert
authors.affiliation: Swiss Center of Regenerative Medicine, University and University Hospital Zürich, Zürich, Switzerland.
authors.forename: Petra E
authors.initials: PE
authors.lastname: Dijkman
authors.affiliation: Swiss Center of Regenerative Medicine, University and University Hospital Zürich, Zürich, Switzerland.
authors.forename: Laura
authors.initials: L
authors.lastname: Frese
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.
authors.forename: Bart
authors.initials: B
authors.lastname: Sanders
authors.affiliation: Swiss Center of Regenerative Medicine, University and University Hospital Zürich, Zürich, Switzerland; Center Surgery, Division of Surgical Research, University Hospital Zürich, Zürich, Switzerland.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Weber
authors.affiliation: Center Surgery, Division of Surgical Research, University Hospital Zürich, Zürich, Switzerland.
authors.forename: Nikola
authors.initials: N
authors.lastname: Cesarovic
authors.affiliation: Center of Applied Biotechnology and Molecular Medicine (CABMM), University of Zürich, Zürich, Switzerland.
authors.forename: Michele
authors.initials: M
authors.lastname: Sidler
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.
authors.forename: Jori
authors.initials: J
authors.lastname: Leenders
authors.affiliation: Heart Center Zürich, University Hospital Zürich, Zürich, Switzerland.
authors.forename: Rolf
authors.initials: R
authors.lastname: Jenni
authors.affiliation: Heart Center Zürich, University Hospital Zürich, Zürich, Switzerland.
authors.forename: Jürg
authors.initials: J
authors.lastname: Grünenfelder
authors.affiliation: Heart Center Zürich, University Hospital Zürich, Zürich, Switzerland.
authors.forename: Volkmar
authors.initials: V
authors.lastname: Falk
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.
authors.forename: Frank P T
authors.initials: FPT
authors.lastname: Baaijens
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands; Swiss Center of Regenerative Medicine, University and University Hospital Zürich, Zürich, Switzerland; Center Surgery, Division of Surgical Research, University Hospital Zürich, Zürich, Switzerland; Heart Center Zürich, University Hospital Zürich, Zürich, Switzerland; Center of Applied Biotechnology and Molecular Medicine (CABMM), University of Zürich, Zürich, Switzerland. Electronic address: simon_philipp.hoerstrup@usz.ch.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Hoerstrup
mesh_terms: D006349:Heart Valve Diseases / Q000601:surgery*; D006350:Heart Valve Prosthesis; D006351:Heart Valves; D006801:Humans; D023822:Tissue Engineering / Q000639:trends*
keywords: off-the-shelf tissue engineering; self-repair; tissue-engineered heart valves; transcatheter valve implantation