Journal
ACTA BIOMATERIALIA
Volume 71, Issue -, Pages 510-521Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2018.02.031
Keywords
Sulfated chitosan; Vascular endothelial growth factor; Affinity; Angiogenesis
Funding
- National Natural Science Foundation of China [31330028, 31470923]
- International Cooperation Project of Shanghai Science and Technique Committee [15520711100]
- Major Basic Research Foundation of Shanghai Science and Technique Committee [14JC1490800]
- Key Project of Logistic Scientific Research of PLA [BWS13C014]
- 111 Project [B14018]
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Emerging evidence suggests that vascular endothelial growth factor (VEGF) is important in the treatment of various ischemic and cardiovascular diseases. However, it often suffers from high cost and easy deactivation with a short half-life. Here, we describe a synthetic 2-N, 6-O-sulfated chitosan (26SCS) with a high affinity to VEGF promoting the binding of the signaling protein to its VEGF receptor 2 (VEGFR2), activating receptor phosphorylation and pro-angiogenic related genes expression, and further stimulating downstream VEGF-dependent endothelial cell viability, migration, tube formation and rat aortic rings outgrowth. Interestingly, the obvious recruitment of mural cells were occurred to stabilize the sprouted microvessels. In addition, the pro-angiogenic potential of 26SCS composited VEGF was confirmed in vivo using the chick embryo chorioallantoic membrane (CAM) assay with an extensive perfusable vascular network. A longer monitoring was administered subcutaneously to mice in a biocompatible gelatin sponge and showed that VEGF with 26SCS had the capability to efficiently enhance neovascularization. These findings highlight that 26SCS, the semi-synthetic natural polymer, may be a promising coagent with VEGF for vascular therapy.
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