Development of a Novel Human Cell-Derived Tissue-Engineered Heart Valve for Transcatheter Aortic Valve Replacement: an In Vitro and In Vivo Feasibility Study.
Lintas VInstitute for Regenerative Medicine (IREM), University of Zurich, Center for Therapy Development/GMP, Zurich, Switzerland.
Fioretta ESInstitute for Regenerative Medicine (IREM), University of Zurich, Center for Therapy Development/GMP, Zurich, Switzerland.
Motta SEInstitute for Regenerative Medicine (IREM), University of Zurich, Center for Therapy Development/GMP, Zurich, Switzerland.
Dijkman PEInstitute for Regenerative Medicine (IREM), University of Zurich, Center for Therapy Development/GMP, Zurich, Switzerland.
Pensalfini MInstitute for Mechanical Systems, Department of Mechanical and Process Engineering, ETH Zurich, Zurich, Switzerland.
Mazza EInstitute for Mechanical Systems, Department of Mechanical and Process Engineering, ETH Zurich, Zurich, Switzerland.
Caliskan EClinic for Cardiac Surgery, University Hospital Zurich, Zurich, Switzerland.
Rodriguez HClinic for Cardiac Surgery, University Hospital Zurich, Zurich, Switzerland.
Lipiski MClinic for Cardiac Surgery, University Hospital Zurich, Zurich, Switzerland.
Sauer MClinic for Cardiac Surgery, University Hospital Zurich, Zurich, Switzerland.
Cesarovic NClinic for Cardiac Surgery, University Hospital Zurich, Zurich, Switzerland.
Hoerstrup SPInstitute for Regenerative Medicine (IREM), University of Zurich, Center for Therapy Development/GMP, Zurich, Switzerland.
Emmert MYInstitute for Regenerative Medicine (IREM), University of Zurich, Center for Therapy Development/GMP, Zurich, Switzerland. maximilian.emmert@usz.ch.
English
Transcatheter aortic valve replacement (TAVR) is being extended to younger patients. However, TAVR-compatible bioprostheses are based on xenogeneic materials with limited durability. Off-the-shelf tissue-engineered heart valves (TEHVs) with remodeling capacity may overcome the shortcomings of current TAVR devices. Here, we develop for the first time a TEHV for TAVR, based on human cell-derived extracellular matrix and integrated into a state-of-the-art stent for TAVR. The TEHVs, characterized by a dense acellular collagenous matrix, demonstrated in vitro functionality under aortic pressure conditions (n = 4). Next, transapical TAVR feasibility and in vivo TEHV functionality were assessed in acute studies (n = 5) in sheep. The valves successfully coped with the aortic environment, showing normal leaflet motion, free coronary flow, and absence of stenosis or paravalvular leak. At explantation, TEHVs presented full structural integrity and initial cell infiltration. Its long-term performance proven, such TEHV could fulfill the need for next-generation lifelong TAVR prostheses.