Scaffolds with covalently immobilized VEGF and Angiopoietin-1 for vascularization of engineered tissues

Abstract The aim of this study was to engineer a biomaterial capable of supporting vascularization in vitro and in vivo . We covalently immobilized vascular endothelial growth factor (VEGF) and Angiopoietin-1 (Ang1) onto three-dimensional porous collagen scaffolds using 1-ethyl-3-[3-dimethylaminopro...

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Veröffentlicht in:Biomaterials 2010-01, Vol.31 (2), p.226-241
Hauptverfasser: Chiu, Loraine L.Y, Radisic, Milica
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Radisic, Milica
description Abstract The aim of this study was to engineer a biomaterial capable of supporting vascularization in vitro and in vivo . We covalently immobilized vascular endothelial growth factor (VEGF) and Angiopoietin-1 (Ang1) onto three-dimensional porous collagen scaffolds using 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC) chemistry. Over both 3 and 7 days in vitro , seeded endothelial cells (ECs) had increased proliferation on scaffolds with immobilized VEGF and/or Ang1 compared to unmodified scaffolds and soluble growth factor controls. Notably, the group with co-immobilized VEGF and Ang1 showed significantly higher cell number ( P = 0.0079), higher overall lactate production rate ( P = 0.0044) and higher overall glucose consumption rate ( P = 0.0034) at Day 3, compared to its corresponding soluble control for which growth factors were added to culture medium. By Day 7, hematoxylin and eosin, live/dead, CD31, and von Willebrand factor staining all showed improved tube formation by ECs when cultivated on scaffolds with co-immobilized growth factors. Interestingly, scaffolds with co-immobilized VEGF and Ang1 showed increased EC infiltration in the chorioallantoic membrane (CAM) assay, compared to scaffolds with independently immobilized VEGF/Ang1. This study presents an alternative method for promoting the formation of vascular structures, via covalent immobilization of angiogenic growth factors that are more stable than soluble ones and have a localized effect.
doi_str_mv 10.1016/j.biomaterials.2009.09.039
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We covalently immobilized vascular endothelial growth factor (VEGF) and Angiopoietin-1 (Ang1) onto three-dimensional porous collagen scaffolds using 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC) chemistry. Over both 3 and 7 days in vitro , seeded endothelial cells (ECs) had increased proliferation on scaffolds with immobilized VEGF and/or Ang1 compared to unmodified scaffolds and soluble growth factor controls. Notably, the group with co-immobilized VEGF and Ang1 showed significantly higher cell number ( P = 0.0079), higher overall lactate production rate ( P = 0.0044) and higher overall glucose consumption rate ( P = 0.0034) at Day 3, compared to its corresponding soluble control for which growth factors were added to culture medium. By Day 7, hematoxylin and eosin, live/dead, CD31, and von Willebrand factor staining all showed improved tube formation by ECs when cultivated on scaffolds with co-immobilized growth factors. Interestingly, scaffolds with co-immobilized VEGF and Ang1 showed increased EC infiltration in the chorioallantoic membrane (CAM) assay, compared to scaffolds with independently immobilized VEGF/Ang1. 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Radisic, Milica</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c464t-9bdf3c982d7544fab23a4aa4cccea792868f6112ff639d085f5627a506f6e2583</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Advanced Basic Science</topic><topic>Angiogenesis</topic><topic>Angiopoietin-1 - pharmacology</topic><topic>Animals</topic><topic>Biological Assay</topic><topic>Cardiac tissue engineering</topic><topic>Cell Line</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell Shape - drug effects</topic><topic>Chickens</topic><topic>Chorioallantoic Membrane - drug effects</topic><topic>Chorioallantoic Membrane - metabolism</topic><topic>Collagen</topic><topic>Collagen - pharmacology</topic><topic>Collagenases - metabolism</topic><topic>Dentistry</topic><topic>Endothelial cell</topic><topic>Endothelial Cells - cytology</topic><topic>Endothelial Cells - drug effects</topic><topic>Endothelial Cells - metabolism</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Growth factors</topic><topic>Hemoglobins - metabolism</topic><topic>Humans</topic><topic>Hydrolysis - drug effects</topic><topic>Immobilized Proteins - pharmacology</topic><topic>Mice</topic><topic>Microscopy, Electron, Scanning</topic><topic>Neovascularization, Physiologic - drug effects</topic><topic>Scaffold</topic><topic>Solubility - drug effects</topic><topic>Tissue Engineering</topic><topic>Tissue Scaffolds - chemistry</topic><topic>Vascular Endothelial Growth Factor A - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chiu, Loraine L.Y</creatorcontrib><creatorcontrib>Radisic, Milica</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Mechanical &amp; 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subjects Advanced Basic Science
Angiogenesis
Angiopoietin-1 - pharmacology
Animals
Biological Assay
Cardiac tissue engineering
Cell Line
Cell Proliferation - drug effects
Cell Shape - drug effects
Chickens
Chorioallantoic Membrane - drug effects
Chorioallantoic Membrane - metabolism
Collagen
Collagen - pharmacology
Collagenases - metabolism
Dentistry
Endothelial cell
Endothelial Cells - cytology
Endothelial Cells - drug effects
Endothelial Cells - metabolism
Enzyme-Linked Immunosorbent Assay
Growth factors
Hemoglobins - metabolism
Humans
Hydrolysis - drug effects
Immobilized Proteins - pharmacology
Mice
Microscopy, Electron, Scanning
Neovascularization, Physiologic - drug effects
Scaffold
Solubility - drug effects
Tissue Engineering
Tissue Scaffolds - chemistry
Vascular Endothelial Growth Factor A - pharmacology
title Scaffolds with covalently immobilized VEGF and Angiopoietin-1 for vascularization of engineered tissues
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