Journal
BIOMATERIALS
Volume 31, Issue 2, Pages 226-241Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2009.09.039
Keywords
Angiogenesis; Cardiac tissue engineering; Endothelial cell; Collagen; Growth factors; Scaffold
Funding
- Canadian Institutes of Health Research (CIHR)
- Heart and Stroke Foundation of Ontario [NA 6077]
- NSERC Alexander Graham Bell Canada
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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-dimethylaminopropy]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. (C) 2009 Elsevier Ltd. All rights reserved.
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