title: Accordion-like honeycombs for tissue engineering of cardiac anisotropy.
abstract: Tissue-engineered grafts may be useful in myocardial repair; however, previous scaffolds have been structurally incompatible with recapitulating cardiac anisotropy. Here, we use microfabrication techniques to create an accordion-like honeycomb microstructure in poly(glycerol sebacate), which yields porous, elastomeric three-dimensional (3D) scaffolds with controllable stiffness and anisotropy. Accordion-like honeycomb scaffolds with cultured neonatal rat heart cells demonstrated utility through: (1) closely matched mechanical properties compared to native adult rat right ventricular myocardium, with stiffnesses controlled by polymer curing time; (2) heart cell contractility inducible by electric field stimulation with directionally dependent electrical excitation thresholds (p<0.05); and (3) greater heart cell alignment (p<0.0001) than isotropic control scaffolds. Prototype bilaminar scaffolds with 3D interconnected pore networks yielded electrically excitable grafts with multi-layered neonatal rat heart cells. Accordion-like honeycombs can thus overcome principal structural-mechanical limitations of previous scaffolds, promoting the formation of grafts with aligned heart cells and mechanical properties more closely resembling native myocardium.
authors.affiliation: Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, E25-330 Cambridge, Massachusetts 02139, USA.
authors.forename: George C
authors.initials: GC
authors.lastname: Engelmayr
authors.forename: Mingyu
authors.initials: M
authors.lastname: Cheng
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Bettinger
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Borenstein
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Freed
mesh_terms: D000818:Animals; D016880:Anisotropy; D001696:Biomechanical Phenomena; D003651:Decanoates / Q000737:chemistry*; D004553:Electric Conductivity; D005990:Glycerol / Q000031:analogs & derivatives* / Q000737:chemistry; D006321:Heart / Q000502:physiology*; D054018:Lasers, Excimer; D009206:Myocardium / Q000166:cytology* / Q000648:ultrastructure; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D023822:Tissue Engineering; D054457:Tissue Scaffolds; D016276:Ventricular Function
chemical_list: D003651:Decanoates; D011108:Polymers; C469892:poly(glycerol-sebacate); D005990:Glycerol