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PMID: 20696917 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Proangiogenic scaffolds as functional templates for cardiac tissue engineering.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 107 ·No. 34 ·2010-08-24 ·Pages 15211-6

Madden LR, Mortisen DJ, Sussman EM, Dupras SK, Fugate JA, Cuy JL, Hauch KD, Laflamme MA, Murry CE, Ratner BD

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.

MeSH Terms
Animals Cell Count Chick Embryo Heart Humans Hydrogels Methacrylates Microscopy, Electron, Scanning Myocytes, Cardiac/cytology,physiology Neovascularization, Physiologic Polyhydroxyethyl Methacrylate Rats Rats, Nude Rats, Sprague-Dawley Tissue Engineering/methods Tissue Scaffolds Ventricular Myosins/metabolism
Chemicals
Hydrogels Methacrylates Polyhydroxyethyl Methacrylate poly(hydroxyethyl methacrylate-methacrylic acid)hydrogel Ventricular Myosins
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Madden Lauran R
Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.
Mortisen Derek J
Sussman Eric M
Dupras Sarah K
Fugate James A
Cuy Janet L
Hauch Kip D
Laflamme Michael A
Murry Charles E
Ratner Buddy D
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.1006442107
Published
2010-08-24
Epub
2010-00-09
Pages
15211-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2930533
Subset
IM
Grants
NHLBI NIH HHS · R01 HL64387 · United States
NHLBI NIH HHS · R01 HL064387 · United States
NHLBI NIH HHS · P01 HL094374 · United States
NIDDK NIH HHS · U24 DK076126 · United States
NHLBI NIH HHS · R01 HL084642 · United States
NIDDK NIH HHS · U24DK076126 · United States
External Links
PubMed source DOI: 10.1073/pnas.1006442107 PMC Full Text View journal details
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