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Repair of bone defects using synthetic mimetics of collagenous extracellular matrices
We have engineered synthetic poly(ethylene glycol) (PEG)–based hydrogels as cell-ingrowth matrices for in situ bone regeneration. These networks contain a combination of pendant oligopeptide ligands for cell adhesion (RGDSP) and substrates for matrix metalloproteinase (MMP) as linkers between PEG ch...
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Published in: | Nature biotechnology 2003-05, Vol.21 (5), p.513-518 |
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container_title | Nature biotechnology |
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creator | Hubbell, Jeffrey A Lutolf, Matthias P Weber, Franz E Schmoekel, Hugo G Schense, Jason C Kohler, Thomas Müller, Ralph |
description | We have engineered synthetic poly(ethylene glycol) (PEG)–based hydrogels as cell-ingrowth matrices for
in situ
bone regeneration. These networks contain a combination of pendant oligopeptide ligands for cell adhesion (RGDSP) and substrates for matrix metalloproteinase (MMP) as linkers between PEG chains. Primary human fibroblasts were shown to migrate within these matrices by integrin- and MMP-dependent mechanisms. Gels used to deliver recombinant human bone morphogenetic protein-2 (rhBMP-2) to the site of critical- sized defects in rat crania were completely infiltrated by cells and were remodeled into bony tissue within five weeks. Bone regeneration was dependent on the proteolytic sensitivity of the matrices and their architecture. The cell-mediated proteolytic invasiveness of the gels and entrapment of rhBMP-2 resulted in efficient and highly localized bone regeneration. |
doi_str_mv | 10.1038/nbt818 |
format | article |
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in situ
bone regeneration. These networks contain a combination of pendant oligopeptide ligands for cell adhesion (RGDSP) and substrates for matrix metalloproteinase (MMP) as linkers between PEG chains. Primary human fibroblasts were shown to migrate within these matrices by integrin- and MMP-dependent mechanisms. Gels used to deliver recombinant human bone morphogenetic protein-2 (rhBMP-2) to the site of critical- sized defects in rat crania were completely infiltrated by cells and were remodeled into bony tissue within five weeks. Bone regeneration was dependent on the proteolytic sensitivity of the matrices and their architecture. The cell-mediated proteolytic invasiveness of the gels and entrapment of rhBMP-2 resulted in efficient and highly localized bone regeneration.</description><identifier>ISSN: 1087-0156</identifier><identifier>EISSN: 1546-1696</identifier><identifier>DOI: 10.1038/nbt818</identifier><identifier>PMID: 12704396</identifier><identifier>CODEN: NABIF9</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Adhesion ; Agriculture ; Animals ; Bioinformatics ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedical Engineering/Biotechnology ; Biomedicine ; Biomimetic Materials - chemical synthesis ; Biotechnology ; Bone Morphogenetic Protein 2 ; Bone Morphogenetic Proteins - pharmacology ; Bone Regeneration - drug effects ; Bone Substitutes - chemical synthesis ; Bone Substitutes - pharmacology ; Coated Materials, Biocompatible - chemical synthesis ; Collagen - chemistry ; Collagen - metabolism ; Culture Techniques - instrumentation ; Culture Techniques - methods ; Extracellular Matrix ; Fundamental and applied biological sciences. Psychology ; Gels ; Infusion Pumps, Implantable ; Invasiveness ; Life Sciences ; Prostheses and Implants ; Rats ; Skull Fractures - pathology ; Skull Fractures - surgery ; Tissue Engineering - instrumentation ; Tissue Engineering - methods ; Transforming Growth Factor beta ; Treatment Outcome</subject><ispartof>Nature biotechnology, 2003-05, Vol.21 (5), p.513-518</ispartof><rights>Springer Nature America, Inc. 2003</rights><rights>2004 INIST-CNRS</rights><rights>COPYRIGHT 2003 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group May 2003</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c589t-f8f59fc33ceefe75521a72df912fc017eb3c31ec247f27fc4d6d60321bee109d3</citedby><cites>FETCH-LOGICAL-c589t-f8f59fc33ceefe75521a72df912fc017eb3c31ec247f27fc4d6d60321bee109d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,2725,27922,27923</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14829715$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12704396$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hubbell, Jeffrey A</creatorcontrib><creatorcontrib>Lutolf, Matthias P</creatorcontrib><creatorcontrib>Weber, Franz E</creatorcontrib><creatorcontrib>Schmoekel, Hugo G</creatorcontrib><creatorcontrib>Schense, Jason C</creatorcontrib><creatorcontrib>Kohler, Thomas</creatorcontrib><creatorcontrib>Müller, Ralph</creatorcontrib><title>Repair of bone defects using synthetic mimetics of collagenous extracellular matrices</title><title>Nature biotechnology</title><addtitle>Nat Biotechnol</addtitle><addtitle>Nat Biotechnol</addtitle><description>We have engineered synthetic poly(ethylene glycol) (PEG)–based hydrogels as cell-ingrowth matrices for
in situ
bone regeneration. These networks contain a combination of pendant oligopeptide ligands for cell adhesion (RGDSP) and substrates for matrix metalloproteinase (MMP) as linkers between PEG chains. Primary human fibroblasts were shown to migrate within these matrices by integrin- and MMP-dependent mechanisms. Gels used to deliver recombinant human bone morphogenetic protein-2 (rhBMP-2) to the site of critical- sized defects in rat crania were completely infiltrated by cells and were remodeled into bony tissue within five weeks. Bone regeneration was dependent on the proteolytic sensitivity of the matrices and their architecture. The cell-mediated proteolytic invasiveness of the gels and entrapment of rhBMP-2 resulted in efficient and highly localized bone regeneration.</description><subject>Adhesion</subject><subject>Agriculture</subject><subject>Animals</subject><subject>Bioinformatics</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedical Engineering/Biotechnology</subject><subject>Biomedicine</subject><subject>Biomimetic Materials - chemical synthesis</subject><subject>Biotechnology</subject><subject>Bone Morphogenetic Protein 2</subject><subject>Bone Morphogenetic Proteins - pharmacology</subject><subject>Bone Regeneration - drug effects</subject><subject>Bone Substitutes - chemical synthesis</subject><subject>Bone Substitutes - pharmacology</subject><subject>Coated Materials, Biocompatible - chemical synthesis</subject><subject>Collagen - chemistry</subject><subject>Collagen - metabolism</subject><subject>Culture Techniques - instrumentation</subject><subject>Culture Techniques - methods</subject><subject>Extracellular Matrix</subject><subject>Fundamental and applied biological sciences. 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Academic</collection><jtitle>Nature biotechnology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hubbell, Jeffrey A</au><au>Lutolf, Matthias P</au><au>Weber, Franz E</au><au>Schmoekel, Hugo G</au><au>Schense, Jason C</au><au>Kohler, Thomas</au><au>Müller, Ralph</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Repair of bone defects using synthetic mimetics of collagenous extracellular matrices</atitle><jtitle>Nature biotechnology</jtitle><stitle>Nat Biotechnol</stitle><addtitle>Nat Biotechnol</addtitle><date>2003-05-01</date><risdate>2003</risdate><volume>21</volume><issue>5</issue><spage>513</spage><epage>518</epage><pages>513-518</pages><issn>1087-0156</issn><eissn>1546-1696</eissn><coden>NABIF9</coden><abstract>We have engineered synthetic poly(ethylene glycol) (PEG)–based hydrogels as cell-ingrowth matrices for
in situ
bone regeneration. These networks contain a combination of pendant oligopeptide ligands for cell adhesion (RGDSP) and substrates for matrix metalloproteinase (MMP) as linkers between PEG chains. Primary human fibroblasts were shown to migrate within these matrices by integrin- and MMP-dependent mechanisms. Gels used to deliver recombinant human bone morphogenetic protein-2 (rhBMP-2) to the site of critical- sized defects in rat crania were completely infiltrated by cells and were remodeled into bony tissue within five weeks. Bone regeneration was dependent on the proteolytic sensitivity of the matrices and their architecture. The cell-mediated proteolytic invasiveness of the gels and entrapment of rhBMP-2 resulted in efficient and highly localized bone regeneration.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>12704396</pmid><doi>10.1038/nbt818</doi><tpages>6</tpages></addata></record> |
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subjects | Adhesion Agriculture Animals Bioinformatics Biological and medical sciences Biomedical and Life Sciences Biomedical Engineering/Biotechnology Biomedicine Biomimetic Materials - chemical synthesis Biotechnology Bone Morphogenetic Protein 2 Bone Morphogenetic Proteins - pharmacology Bone Regeneration - drug effects Bone Substitutes - chemical synthesis Bone Substitutes - pharmacology Coated Materials, Biocompatible - chemical synthesis Collagen - chemistry Collagen - metabolism Culture Techniques - instrumentation Culture Techniques - methods Extracellular Matrix Fundamental and applied biological sciences. Psychology Gels Infusion Pumps, Implantable Invasiveness Life Sciences Prostheses and Implants Rats Skull Fractures - pathology Skull Fractures - surgery Tissue Engineering - instrumentation Tissue Engineering - methods Transforming Growth Factor beta Treatment Outcome |
title | Repair of bone defects using synthetic mimetics of collagenous extracellular matrices |
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