Proangiogenic scaffolds as functional templates for cardiac tissue engineering
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) h...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2010-08, Vol.107 (34), p.15211-15216 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Madden, Lauran R. 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. Langer, Robert |
| description | 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 μm 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. |
| doi_str_mv | 10.1073/pnas.1006442107 |
| format | Article |
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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 μm 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.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1006442107</identifier><identifier>PMID: 20696917</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Angiogenesis ; Animals ; Biological Sciences ; Cardiac muscle ; cardiomyocytes ; Cell Count ; Cell culture ; Channel pores ; Chick Embryo ; Embryonic stem cells ; Endothelial cells ; Heart ; Humans ; Hydrogels ; Inflammation ; Integration ; Macrophages ; Mass transfer ; Methacrylates ; Microscopy, Electron, Scanning ; Muscles ; Myocardium ; Myocytes, Cardiac - cytology ; Myocytes, Cardiac - physiology ; Neovascularization, Physiologic ; Phenotypes ; Polyhydroxyethyl Methacrylate ; Rats ; Rats, Nude ; Rats, Sprague-Dawley ; Scaffolds ; Stem cells ; Stroma ; Tissue engineering ; Tissue Engineering - methods ; Tissue Scaffolds ; vascularization ; Ventricular Myosins - metabolism</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2010-08, Vol.107 (34), p.15211-15216</ispartof><rights>Copyright © 1993-2008 The National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Aug 24, 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c564t-b82fe3d3de546e6390b005f87593b1d4d1c4c42d265f3534365bee666e4c9abb3</citedby><cites>FETCH-LOGICAL-c564t-b82fe3d3de546e6390b005f87593b1d4d1c4c42d265f3534365bee666e4c9abb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/107/34.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/27862219$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/27862219$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27903,27904,53769,53771,57995,58228</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20696917$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Madden, Lauran R.</creatorcontrib><creatorcontrib>Mortisen, Derek J.</creatorcontrib><creatorcontrib>Sussman, Eric M.</creatorcontrib><creatorcontrib>Dupras, Sarah K.</creatorcontrib><creatorcontrib>Fugate, James A.</creatorcontrib><creatorcontrib>Cuy, Janet L.</creatorcontrib><creatorcontrib>Hauch, Kip D.</creatorcontrib><creatorcontrib>Laflamme, Michael A.</creatorcontrib><creatorcontrib>Murry, Charles E.</creatorcontrib><creatorcontrib>Ratner, Buddy D.</creatorcontrib><creatorcontrib>Langer, Robert</creatorcontrib><title>Proangiogenic scaffolds as functional templates for cardiac tissue engineering</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>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 μm 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.</description><subject>Angiogenesis</subject><subject>Animals</subject><subject>Biological Sciences</subject><subject>Cardiac muscle</subject><subject>cardiomyocytes</subject><subject>Cell Count</subject><subject>Cell culture</subject><subject>Channel pores</subject><subject>Chick Embryo</subject><subject>Embryonic stem cells</subject><subject>Endothelial cells</subject><subject>Heart</subject><subject>Humans</subject><subject>Hydrogels</subject><subject>Inflammation</subject><subject>Integration</subject><subject>Macrophages</subject><subject>Mass transfer</subject><subject>Methacrylates</subject><subject>Microscopy, Electron, Scanning</subject><subject>Muscles</subject><subject>Myocardium</subject><subject>Myocytes, Cardiac - cytology</subject><subject>Myocytes, Cardiac - physiology</subject><subject>Neovascularization, Physiologic</subject><subject>Phenotypes</subject><subject>Polyhydroxyethyl Methacrylate</subject><subject>Rats</subject><subject>Rats, Nude</subject><subject>Rats, Sprague-Dawley</subject><subject>Scaffolds</subject><subject>Stem cells</subject><subject>Stroma</subject><subject>Tissue engineering</subject><subject>Tissue Engineering - methods</subject><subject>Tissue Scaffolds</subject><subject>vascularization</subject><subject>Ventricular Myosins - metabolism</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkbtvFDEQxq0IlBwhdSqiVRqqJX4_GqQo4iVFQAG15fXOHj7t2Rd7Fyn_PV7dkQMaqhmNf9-n8XwIXRL8hmDFbnbRldphyTmtgxO0ItiQVnKDn6EVxlS1mlN-hl6UssEYG6HxKTqjWBppiFqhz19zcnEd0hpi8E3xbhjS2JfGlWaYo59Cim5sJtjuRjdBHabceJf74HwzhVJmaKDqI0AOcf0SPR_cWODiUM_R9_fvvt19bO-_fPh0d3vfeiH51HaaDsB61oPgEiQzuMNYDFoJwzrS85547jntqRQDE4wzKToAKSVwb1zXsXP0du-7m7st9B7ilN1odzlsXX60yQX790sMP-w6_bTUMCwYqwavDwY5PcxQJrsNxcM4ughpLlZLpZjiTP2XVFwbrSmjlbz-h9ykOdfzLZBaTs91hW72kM-plAzD09IE2yVTu2Rqj5lWxdWff33if4dYgeYALMqjnbKMWyIoIRV5tUc2ZUr5aKG0pJQY9guRqLJb</recordid><startdate>20100824</startdate><enddate>20100824</enddate><creator>Madden, Lauran R.</creator><creator>Mortisen, Derek J.</creator><creator>Sussman, Eric M.</creator><creator>Dupras, Sarah K.</creator><creator>Fugate, James A.</creator><creator>Cuy, Janet L.</creator><creator>Hauch, Kip D.</creator><creator>Laflamme, Michael A.</creator><creator>Murry, Charles E.</creator><creator>Ratner, Buddy D.</creator><creator>Langer, Robert</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>7QO</scope><scope>5PM</scope></search><sort><creationdate>20100824</creationdate><title>Proangiogenic scaffolds as functional templates for cardiac tissue engineering</title><author>Madden, Lauran R. ; 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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 μm showed angiogenesis and reduced fibrotic response, coinciding with a shift in macrophage phenotype toward the M2 state. 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| subjects | Angiogenesis Animals Biological Sciences Cardiac muscle cardiomyocytes Cell Count Cell culture Channel pores Chick Embryo Embryonic stem cells Endothelial cells Heart Humans Hydrogels Inflammation Integration Macrophages Mass transfer Methacrylates Microscopy, Electron, Scanning Muscles Myocardium Myocytes, Cardiac - cytology Myocytes, Cardiac - physiology Neovascularization, Physiologic Phenotypes Polyhydroxyethyl Methacrylate Rats Rats, Nude Rats, Sprague-Dawley Scaffolds Stem cells Stroma Tissue engineering Tissue Engineering - methods Tissue Scaffolds vascularization Ventricular Myosins - metabolism |
| title | Proangiogenic scaffolds as functional templates for cardiac tissue engineering |
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