The impact of proteinase-induced matrix degradation on the release of VEGF from heparinized collagen matrices

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Title: The impact of proteinase-induced matrix degradation on the release of VEGF from heparinized collagen matrices
Authors: Yao, Chang1, Roderfeld, Martin2, Rath, Timo2, Roeb, Elke2, Bernhagen, Jürgen1, Steffens, Guy1 gcm.steffens@post.rwth-aachen.de
Source: Biomaterials. Mar2006, Vol. 27 Issue 8, p1608-1616. 9p.
Subjects: Connective tissues, Cytokines, Peptides, Heparin
Abstract: Abstract: The in vivo application of engineered matrices in human wound healing processes is often hampered by the slow rate of vascularization. Therefore much research is directed towards enhancing the angiogenic properties of such matrices. One approach for enhancing the vascularization is the incorporation of angiogenic growth factors. Recently, we and others have reported on immobilizing such factors into collagen matrices either by covalent attachment or by physical binding to covalently incorporated heparin. Especially the latter procedure has been shown to lead to substantial increase rates in vascularization in in vivo experiments. The increases have been proposed to depend on the sustained release of the incorporated angiogenic growth factors from the heparinized collagen matrices. In this paper, we report on investigations to study the release of vascular endothelial growth factor (VEGF) from collagen matrices under conditions which mimic potential in vivo situations. Relevant proteinase concentrations were deduced from in vitro experiments in which we evaluated the secretion of selected matrix metalloproteinases from fibroblasts in contact with collagen. The release of VEGF from non-modified, cross-linked and heparinized collagen matrices in the absence and in the presence of varying concentrations of proteinases was then determined by ELISA and liquid scintillation counting. The release behaviour appears to be controlled by both the presence of heparin and the levels of proteinases applied. Experiments with matrices containing radioactively labelled heparin suggest that VEGF release results from the consecutive and simultaneous release of three species of VEGF molecules that differ in their binding affinities to the differently modified collagen matrices. The species binding specifically to heparin most likely accounts for the previously observed increases in angiogenic potential between loading VEGF to non-heparinized and heparinized collagen matrices. [Copyright &y& Elsevier]
Copyright of Biomaterials is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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DbLabel: Engineering Source
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  Data: The impact of proteinase-induced matrix degradation on the release of VEGF from heparinized collagen matrices
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  Data: <searchLink fieldCode="AR" term="%22Yao%2C+Chang%22">Yao, Chang</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Roderfeld%2C+Martin%22">Roderfeld, Martin</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Rath%2C+Timo%22">Rath, Timo</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Roeb%2C+Elke%22">Roeb, Elke</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Bernhagen%2C+Jürgen%22">Bernhagen, Jürgen</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Steffens%2C+Guy%22">Steffens, Guy</searchLink><relatesTo>1</relatesTo><i> gcm.steffens@post.rwth-aachen.de</i>
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  Data: <searchLink fieldCode="JN" term="%22Biomaterials%22">Biomaterials</searchLink>. Mar2006, Vol. 27 Issue 8, p1608-1616. 9p.
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  Data: <searchLink fieldCode="DE" term="%22Connective+tissues%22">Connective tissues</searchLink><br /><searchLink fieldCode="DE" term="%22Cytokines%22">Cytokines</searchLink><br /><searchLink fieldCode="DE" term="%22Peptides%22">Peptides</searchLink><br /><searchLink fieldCode="DE" term="%22Heparin%22">Heparin</searchLink>
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  Data: Abstract: The in vivo application of engineered matrices in human wound healing processes is often hampered by the slow rate of vascularization. Therefore much research is directed towards enhancing the angiogenic properties of such matrices. One approach for enhancing the vascularization is the incorporation of angiogenic growth factors. Recently, we and others have reported on immobilizing such factors into collagen matrices either by covalent attachment or by physical binding to covalently incorporated heparin. Especially the latter procedure has been shown to lead to substantial increase rates in vascularization in in vivo experiments. The increases have been proposed to depend on the sustained release of the incorporated angiogenic growth factors from the heparinized collagen matrices. In this paper, we report on investigations to study the release of vascular endothelial growth factor (VEGF) from collagen matrices under conditions which mimic potential in vivo situations. Relevant proteinase concentrations were deduced from in vitro experiments in which we evaluated the secretion of selected matrix metalloproteinases from fibroblasts in contact with collagen. The release of VEGF from non-modified, cross-linked and heparinized collagen matrices in the absence and in the presence of varying concentrations of proteinases was then determined by ELISA and liquid scintillation counting. The release behaviour appears to be controlled by both the presence of heparin and the levels of proteinases applied. Experiments with matrices containing radioactively labelled heparin suggest that VEGF release results from the consecutive and simultaneous release of three species of VEGF molecules that differ in their binding affinities to the differently modified collagen matrices. The species binding specifically to heparin most likely accounts for the previously observed increases in angiogenic potential between loading VEGF to non-heparinized and heparinized collagen matrices. [Copyright &y& Elsevier]
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  Data: <i>Copyright of Biomaterials is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1016/j.biomaterials.2005.08.037
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        Text: English
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      – SubjectFull: Peptides
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              Text: Mar2006
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