title: Current progress in tissue engineering of heart valves: multiscale problems, multiscale solutions.
abstract: BACKGROUND
  Heart valve disease is an increasingly prevalent and clinically serious condition. There are no clinically effective biological diagnostics or treatment strategies. The only recourse available is replacement with a prosthetic valve, but the inability of these devices to grow or respond biologically to their environments necessitates multiple resizing surgeries and life-long coagulation treatment, especially in children. Tissue engineering has a unique opportunity to impact heart valve disease by providing a living valve conduit, capable of growth and biological integration.
  
  
  METHODS
  This review will cover current tissue engineering strategies in fabricating heart valves and their progress towards the clinic, including molded scaffolds using naturally derived or synthetic polymers, decellularization, electrospinning, 3D bioprinting, hybrid techniques, and in vivo engineering.
  
  
  CONCLUSIONS
  Whereas much progress has been made to create functional living heart valves, a clinically viable product is not yet realized. The next leap in engineered living heart valves will require a deeper understanding of how the natural multi-scale structural and biological heterogeneity of the tissue ensures its efficient function. Related, improved fabrication strategies must be developed that can replicate this de novo complexity, which is likely instructive for appropriate cell differentiation and remodeling whether seeded with autologous stem cells in vitro or endogenously recruited cells.
authors.affiliation: Cornell University, Department of Biomedical Engineering , Ithaca, NY , USA jtb47@cornell.edu.
authors.forename: Daniel Y
authors.initials: DY
authors.lastname: Cheung
authors.forename: Bin
authors.initials: B
authors.lastname: Duan
authors.forename: Jonathan T
authors.initials: JT
authors.lastname: Butcher
mesh_terms: D000818:Animals; D006349:Heart Valve Diseases / Q000175:diagnosis / Q000601:surgery; D006350:Heart Valve Prosthesis / Q000639:trends*; D019918:Heart Valve Prosthesis Implantation / Q000379:methods / Q000639:trends; D006351:Heart Valves / Q000473:pathology / Q000601:surgery*; D006801:Humans; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry; D023822:Tissue Engineering / Q000379:methods / Q000639:trends*; D054457:Tissue Scaffolds / Q000737:chemistry / Q000639:trends
chemical_list: D011108:Polymers
keywords: 3D tissue printing; biomechanics; material heterogeneity; stem cells