title: Proangiogenic scaffolds as functional templates for cardiac tissue engineering.
abstract: We demonstrate here a cardiac tissue-engineering strategy addressing multicellular organization, integration into host myocardium, and directional cues to reconstruct the functional architecture of heart muscle. Microtemplating is used to shape poly(2-hydroxyethyl methacrylate-co-methacrylic acid) hydrogel into a tissue-engineering scaffold with architectures driving heart tissue integration. The construct contains parallel channels to organize cardiomyocyte bundles, supported by micrometer-sized, spherical, interconnected pores that enhance angiogenesis while reducing scarring. Surface-modified scaffolds were seeded with human ES cell-derived cardiomyocytes and cultured in vitro. Cardiomyocytes survived and proliferated for 2 wk in scaffolds, reaching adult heart densities. Cardiac implantation of acellular scaffolds with pore diameters of 30-40 microm showed angiogenesis and reduced fibrotic response, coinciding with a shift in macrophage phenotype toward the M2 state. This work establishes a foundation for spatially controlled cardiac tissue engineering by providing discrete compartments for cardiomyocytes and stroma in a scaffold that enhances vascularization and integration while controlling the inflammatory response.
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.
authors.forename: Lauran R
authors.initials: LR
authors.lastname: Madden
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Mortisen
authors.forename: Eric M
authors.initials: EM
authors.lastname: Sussman
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Dupras
authors.forename: James A
authors.initials: JA
authors.lastname: Fugate
authors.forename: Janet L
authors.initials: JL
authors.lastname: Cuy
authors.forename: Kip D
authors.initials: KD
authors.lastname: Hauch
authors.forename: Michael A
authors.initials: MA
authors.lastname: Laflamme
authors.forename: Charles E
authors.initials: CE
authors.lastname: Murry
authors.forename: Buddy D
authors.initials: BD
authors.lastname: Ratner
mesh_terms: D000818:Animals; D002452:Cell Count; D002642:Chick Embryo; D006321:Heart; D006801:Humans; D020100:Hydrogels; D008689:Methacrylates; D008855:Microscopy, Electron, Scanning; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000502:physiology*; D018919:Neovascularization, Physiologic; D011102:Polyhydroxyethyl Methacrylate; D051381:Rats; D011923:Rats, Nude; D017207:Rats, Sprague-Dawley; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D024723:Ventricular Myosins / Q000378:metabolism
chemical_list: D020100:Hydrogels; D008689:Methacrylates; D011102:Polyhydroxyethyl Methacrylate; C059480:poly(hydroxyethyl methacrylate-methacrylic acid)hydrogel; D024723:Ventricular Myosins