Tissue substitutes with improved angiogenic capabilities: an in vitro investigation with endothelial cells and endothelial progenitor cells. Cells Tissues Organs. 2010;191(2):96-104 Authors: Grieb G, Groger A, Piatkowski A, Markowicz M, Steffens GC, Pallua N The use of implantable biomaterials, such as artificial skin substitutes used for dermal defects, remains limited by the low angiogenic potential o! f these products. The rapid in vivo degradation of growth factors contributes to the limiting of angiogenesis in biomaterials. Here, we report on collagen sponges in which vascular endothelial growth factor (VEGF) was immobilized through physical binding to heparin, covalently incorporated in the matrix via cross-linking with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide. The in vitro release of VEGF over time and endothelial cell proliferation were investigated in matrices modified at varying heparin to EDC ratios either nonloaded or loaded with VEGF. ELISA demonstrated a significantly slower in vitro release of VEGF over a period of 5 days from heparinized matrices as compared to their unmodified and cross-linked counterparts. The effects of these modifications on the proliferation of endothelial cells and endothelial progenitor cells were evaluated after 1, 3 and 5 days either according to the bromodeoxyuridine assay or total cell counting ! with a Neubauer chamber. The endothelial and endothelial proge! nitor ce lls cultured in contact with heparinized matrices loaded with VEGF revealed both the highest rate of DNA synthesis and the highest total cell count. Furthermore, these results show that the cross-linking of collagen matrices - both in the presence and absence of heparin - leads to increases of the proliferative activities. We can assume that these changes lead to matrices with increased angiogenic capabilities. PMID: 19641290 [PubMed - indexed for MEDLINE] |
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