期刊
BIOMATERIALS
卷 35, 期 7, 页码 2149-2161出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2013.11.054
关键词
Angiogenesis; Cell encapsulation; ECM; Growth factors; Hydrogel
资金
- National Institutes of Health [NIH R01 HL093282-01A1, NIH R21 EB016381-01, NIH 1UH2 TR000506-01]
- Biotechnology Training Program [NIGMS 5T32GM08349]
- National Magnetic Resonance Facility at Madison
- NIH (BRTP/NCRR) [P41RR02301]
- NIGMS [P41GM10399]
- University of Wisconsin
- NIH [RR02781, RR08438]
- NSF [DMB-8415048, OIA-9977486, BIR-9214394]
- DOE
- USDA
- NIH (NCRR) [S100RR027000]
Efficient biomaterial screening platforms can test a wide range of extracellular environments that modulate vascular growth. Here, we used synthetic hydrogel arrays to probe the combined effects of Cys-Arg-Gly-Asp-Ser (CRGDS) cell adhesion peptide concentration, shear modulus and vascular endothelial growth factor receptor 2 (VEGFR2) inhibition on human umbilical vein endothelial cell (HUVEC) viability, proliferation and tubulogenesis. HUVECs were encapsulated in degradable poly(ethylene glycol) (PEG) hydrogels with defined CRGDS concentration and shear modulus. VEGFR2 activity was modulated using the VEGFR2 inhibitor SU5416. We demonstrate that synergy exists between VEGFR2 activity and CRGDS ligand presentation in the context of maintaining HUVEC viability. However, excessive CRGDS disrupts this synergy. HUVEC proliferation significantly decreased with VEGFR2 inhibition and increased modulus, but did not vary monotonically with CRGDS concentration. Capillary-like structure (CLS) formation was highly modulated by CRGDS concentration and modulus, but was largely unaffected by VEGFR2 inhibition. We conclude that the characteristics of the ECM surrounding encapsulated HUVECs significantly influence cell viability, proliferation and CLS formation. Additionally, the ECM modulates the effects of VEGFR2 signaling, ranging from changing the effectiveness of synergistic interactions between integrins and VEGFR2 to determining whether VEGFR2 upregulates, downregulates or has no effect on proliferation and CLS formation. (C) 2013 Elsevier Ltd. All rights reserved.
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