Off-the-shelf human decellularized tissue-engineered heart valves in a non-human primate model Benedikt Weber a, b, c,1 , Petra E. Dijkman d,1 , Jacques Scherman c, e, f,1 , Bart Sanders d , Maximilian Y. Emmert a, b, c , Jürg Grünenfelder b, c , Renier Verbeek e, f , Mona Bracher f , Melanie Black f , Thomas Franz e, f, g , Jeroen Kortsmit e, f , Peter Modregger h, i , Silvia Peter h, j , Marco Stampanoni h, j , Jérôme Robert a, b , Debora Kehl a, b , Marina van Doeselaar d , Martin Schweiger a, b, c , Chad E. Brokopp a, b , Thomas Wälchli a, b, k , Volkmar Falk b, c , Peter Zilla e, f , Anita Driessen-Mol d , Frank P.T. Baaijens d , Simon P. Hoerstrup a, b, c, d, * a Swiss Center of Regenerative Medicine, University of Zürich, Moussonstrasse 13, CH-8091 Zürich, Switzerland b Division of Surgical Research, University Hospital of Zurich, Raemistrasse 100, CH-8091 Zürich, Switzerland c Clinic for Cardiovascular Surgery, University Hospital of Zurich, Moussonstrasse 13, CH-8091 Zürich, Switzerland d Department of Biomedical Engineering, Soft Tissue Biomechanics and Tissue Engineering, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands e Chris Barnard Division of Cardiothoracic Surgery, Groote Schuur Hospital, University of Cape Town, South Africa f Cardiovascular Research Unit, Cape Heart Centre, University of Cape Town, South Africa g Programme for the Enhancement of Research Capacity, Research Office, University of Cape Town, Mowbray, South Africa h Swiss Light Source, Paul Scherrer Institute, 5232 Villigen, Switzerland i University of Lausanne, School of Biology and Medicine, Rue du Bugnon 21, CH-1015 Lausanne, Switzerland j Institute for Biomedical Engineering, University and ETH Zurich, ETZ-F-85, Gloriastrasse 35, 8092 Zurich, Switzerland k Department of Health Sciences and Technology, Swiss Federal Institute of Technology Zurich, CH-8057 Zurich, Switzerland article info Article history: Received 18 April 2013 Accepted 27 April 2013 Available online 28 June 2013 Keywords: Heart valve tissue engineering Tissue regeneration Decellularization Preclinical in vivo model Minimally invasive Homologous valve replacement abstract Heart valve tissue engineering based on decellularized xenogenic or allogenic starter matrices has shown promising first clinical results. However, the availability of healthy homologous donor valves is limited and xenogenic materials are associated with infectious and immunologic risks. To address such limitations, biodegradable synthetic materials have been successfully used for the creation of living autologous tissue- engineered heart valves (TEHVs) in vitro. Since these classical tissue engineering technologies necessitate substantial infrastructure and logistics, we recently introduced decellularized TEHVs (dTEHVs), based on biodegradable synthetic materials and vascular-derived cells, and successfully created a potential off-the- shelf starter matrix for guided tissue regeneration. Here, we investigate the host repopulation capacity of such dTEHVs in a non-human primate model with up to 8 weeks follow-up. After minimally invasive de- livery into the orthotopic pulmonary position, dTEHVs revealed mobile and thin leaflets after 8 weeks of follow-up. Furthermore, mild-moderate valvular insufficiency and relative leaflet shortening were detected. However, in comparison to the decellularized human native heart valve control e representing currently used homografts e dTEHVs showed remarkable rapid cellular repopulation. Given this sub- stantial in situ remodeling capacity, these results suggest that human cell-derived bioengineered decel- lularized materials represent a promising and clinically relevant starter matrix for heart valve tissue engineering. These biomaterials may ultimately overcome the limitations of currently used valve re- placements by providing homologous, non-immunogenic, off-the-shelf replacement constructs. Ó 2013 Elsevier Ltd. All rights reserved. 1. Introduction In spite of the major advances with regard to minimally invasive catheter-based approaches, valvular heart disease remains to be a significant global health problem with increasing morbidity and mortality in the developing world as well as industrialized countries * Corresponding author. Swiss Center for Regenerative Medicine, University of Zurich, Moussonstrasse 13, 8091 CH-Zürich, Switzerland. Tel.: þ41 44 255 3644; fax: þ41 44 255 43. E-mail address: simon_philipp.hoerstrup@usz.ch (S.P. Hoerstrup). 1 These authors contributed equally to the paper. Contents lists available at SciVerse ScienceDirect Biomaterials journal homepage: www.elsevier.com/locate/biomaterials 0142-9612/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.biomaterials.2013.04.059 Biomaterials 34 (2013) 7269e7280