title: Tri-layered elastomeric scaffolds for engineering heart valve leaflets.
abstract: Tissue engineered heart valves (TEHVs) that can grow and remodel have the potential to serve as permanent replacements of the current non-viable prosthetic valves particularly for pediatric patients. A major challenge in designing functional TEHVs is to mimic both structural and anisotropic mechanical characteristics of the native valve leaflets. To establish a more biomimetic model of TEHV, we fabricated tri-layered scaffolds by combining electrospinning and microfabrication techniques. These constructs were fabricated by assembling microfabricated poly(glycerol sebacate) (PGS) and fibrous PGS/poly(caprolactone) (PCL) electrospun sheets to develop elastic scaffolds with tunable anisotropic mechanical properties similar to the mechanical characteristics of the native heart valves. The engineered scaffolds supported the growth of valvular interstitial cells (VICs) and mesenchymal stem cells (MSCs) within the 3D structure and promoted the deposition of heart valve extracellular matrix (ECM). MSCs were also organized and aligned along the anisotropic axes of the engineered tri-layered scaffolds. In addition, the fabricated constructs opened and closed properly in an ex vivo model of porcine heart valve leaflet tissue replacement. The engineered tri-layered scaffolds have the potential for successful translation towards TEHV replacements.
authors.affiliation: Biomaterials Innovation Research Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, 65 Landsdowne Street, Cambridge, MA 02139, USA; Department of Cardiac Surgery, Boston Children's Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Bioengineering, The Pennsylvania State University, 205 Hallowell Building, State College, PA 16802, USA; Harvard-MIT Division of Health Sciences and Technology and The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA.
authors.forename: Nafiseh
authors.initials: N
authors.lastname: Masoumi
authors.affiliation: Biomaterials Innovation Research Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, 65 Landsdowne Street, Cambridge, MA 02139, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, 3 Blackfan Circle, Boston, MA 02115, USA.
authors.forename: Nasim
authors.initials: N
authors.lastname: Annabi
authors.affiliation: Biomaterials Innovation Research Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, 65 Landsdowne Street, Cambridge, MA 02139, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, 3 Blackfan Circle, Boston, MA 02115, USA; Department of Cardiovascular Surgery and Research Group for Experimental Surgery, Heinrich Heine University, Medical Faculty, Moorenstr. 5, Dusseldorf 40225, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Assmann
authors.affiliation: Harvard-MIT Division of Health Sciences and Technology and The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA.
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Larson
authors.affiliation: Biomaterials Innovation Research Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, 65 Landsdowne Street, Cambridge, MA 02139, USA; Department of Cardiothoracic Surgery, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, Netherlands.
authors.forename: Jesper
authors.initials: J
authors.lastname: Hjortnaes
authors.affiliation: Biomaterials Innovation Research Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, 65 Landsdowne Street, Cambridge, MA 02139, USA.
authors.forename: Neslihan
authors.initials: N
authors.lastname: Alemdar
authors.affiliation: Biomaterials Innovation Research Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, 65 Landsdowne Street, Cambridge, MA 02139, USA.
authors.forename: Mahshid
authors.initials: M
authors.lastname: Kharaziha
authors.affiliation: Department of Bioengineering, The Pennsylvania State University, 205 Hallowell Building, State College, PA 16802, USA.
authors.forename: Keefe B
authors.initials: KB
authors.lastname: Manning
authors.affiliation: Department of Cardiac Surgery, Boston Children's Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA. Electronic address: John.Mayer@cardio.chboston.org.
authors.forename: John E
authors.initials: JE
authors.lastname: Mayer
authors.affiliation: Biomaterials Innovation Research Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, 65 Landsdowne Street, Cambridge, MA 02139, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, 3 Blackfan Circle, Boston, MA 02115, USA; Department of Physics, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21569, Saudi Arabia. Electronic address: alik@rics.bwh.harvard.edu.
authors.forename: Ali
authors.initials: A
authors.lastname: Khademhosseini
mesh_terms: D000818:Animals; D016880:Anisotropy; D001021:Aortic Valve / Q000187:drug effects / Q000502:physiology; D020724:Elastomers; D006350:Heart Valve Prosthesis; D006801:Humans; D066298:In Vitro Techniques; D008422:Materials Testing; D008855:Microscopy, Electron, Scanning; D011108:Polymers / Q000494:pharmacology*; D011664:Pulmonary Valve / Q000187:drug effects / Q000502:physiology; D012756:Sheep; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D020724:Elastomers; D011108:Polymers; C036925:elastomeric polymer
keywords: Anisotropic mechanical properties; Biodegradable scaffold; Electrospinning; Heart valve tissue engineering; Microfabricated elastomer