title: Three-dimensional elastomeric scaffolds designed with cardiac-mimetic structural and mechanical features.
abstract: Tissue-engineered constructs, at the interface of material science, biology, engineering, and medicine, have the capacity to improve outcomes for cardiac patients by providing living cells and degradable biomaterials that can regenerate the native myocardium. With an ultimate goal of both delivering cells and providing mechanical support to the healing heart, we designed three-dimensional (3D) elastomeric scaffolds with (1) stiffnesses and anisotropy mimicking explanted myocardial specimens as predicted by finite-element (FE) modeling, (2) systematically varied combinations of rectangular pore pattern, pore aspect ratio, and strut width, and (3) structural features approaching tissue scale. Based on predicted mechanical properties, three scaffold designs were selected from eight candidates for fabrication from poly(glycerol sebacate) by micromolding from silicon wafers. Large 20×20 mm scaffolds with high aspect ratio features (5:1 strut height:strut width) were reproducibly cast, cured, and demolded at a relatively high throughput. Empirically measured mechanical properties demonstrated that scaffolds were cardiac mimetic and validated FE model predictions. Two-layered scaffolds providing fully interconnected pore networks were fabricated by layer-by-layer assembly. C2C12 myoblasts cultured on one-layered scaffolds exhibited specific patterns of cell elongation and interconnectivity that appeared to be guided by the scaffold pore pattern. Neonatal rat heart cells cultured on two-layered scaffolds for 1 week were contractile, both spontaneously and in response to electrical stimulation, and expressed sarcomeric α-actinin, a cardiac biomarker. This work not only demonstrated several scaffold designs that promoted functional assembly of rat heart cells, but also provided the foundation for further computational and empirical investigations of 3D elastomeric scaffolds for cardiac tissue engineering.
authors.affiliation: Harvard-MIT Division of Health Sciences and Technology, David H. Koch Institute for Integrative Cancer Research, and Institute for Medical Engineering and Science, Massachusetts Institute of Technology , Cambridge, Massachusetts, USA.
authors.forename: Rebekah A
authors.initials: RA
authors.lastname: Neal
authors.forename: Aurélie
authors.initials: A
authors.lastname: Jean
authors.forename: Hyoungshin
authors.initials: H
authors.lastname: Park
authors.forename: Patrick B
authors.initials: PB
authors.lastname: Wu
authors.forename: James
authors.initials: J
authors.lastname: Hsiao
authors.forename: George C
authors.initials: GC
authors.lastname: Engelmayr
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Freed
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D016880:Anisotropy; D015415:Biomarkers / Q000378:metabolism; D001696:Biomechanical Phenomena / Q000187:drug effects; D040761:Biomimetic Materials / Q000494:pharmacology*; D002460:Cell Line; D003651:Decanoates / Q000494:pharmacology; D020724:Elastomers; D020342:Finite Element Analysis; D005990:Glycerol / Q000031:analogs & derivatives / Q000494:pharmacology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011108:Polymers / Q000494:pharmacology*; D051381:Rats; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D015415:Biomarkers; D003651:Decanoates; D020724:Elastomers; D011108:Polymers; C036925:elastomeric polymer; C469892:poly(glycerol-sebacate); D005990:Glycerol