The promotion of endothelial cell attachment and spreading using FNIII10 fused 
to VEGF-A165

Traub, S.; Morgner, J.; Martino, M. M.; Honing, S.; Swartz, M. A.; Wickström, S. A.; Hubbell, J. A.; Eming, S. A.

doi:10.1016/j.biomaterials.2013.04.050

Item

ITEM ACTIONSEXPORT

Add to Basket

Local TagsRelease HistoryDetailsSummary

Released

Journal Article

The promotion of endothelial cell attachment and spreading using FNIII10 fused to VEGF-A165

MPS-Authors

/persons/resource/persons129350

Wickström, S. A.
Wickström – Skin Homeostasis and Ageing, Max Planck Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society;

External Resource

http://www.ncbi.nlm.nih.gov/pubmed/23683723
(Any fulltext)

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

Fulltext (public)

There are no public fulltexts stored in PuRe

Supplementary Material (public)

There is no public supplementary material available

Citation

Traub, S., Morgner, J., Martino, M. M., Honing, S., Swartz, M. A., Wickström, S. A., et al. (2013). The promotion of endothelial cell attachment and spreading using FNIII10 fused to VEGF-A165. Biomaterials, 34(24), 5958-68. doi:10.1016/j.biomaterials.2013.04.050.

Cite as: https://hdl.handle.net/21.11116/0000-000B-6E3D-7

Abstract

Synergy in the downstream signaling pathways of the vascular endothelial growth factor receptor-2 (VEGFR-2) and the integrin alphavbeta3 is critical for blood vessel formation. Thus, agents that activate both receptors could possess efficient pro-angiogenic potential. Here, we created a fibrin-binding bi-functional protein (FNIII10-VEGF) consisting of the 10th type III domain of fibronectin (FNIII10) fused to a plasmin-resistant VEGF-A165 mutant (VEGF) that potentiated angiogenic processes when compared to the effect of the separate molecules. FNIII10-VEGF was able to bind both VEGFR-2 and integrin alphavbeta3. Intriguingly, cell attachment and spreading to immobilized FNIII10-VEGF was significantly enhanced compared to individual FNIII10 or VEGF proteins. Delivery of immobilized FNIII10-VEGF by covalent linkage to a fibrin matrix significantly enhanced the angiogenic response in an in vivo wound healing assay compared to soluble VEGF. Unexpectedly, the angiogenic response to fibrin-immobilized FNIII10-VEGF was reduced in comparison to the pro-angiogenic effect of fibrin-immobilized VEGF. Collectively, findings of this study corroborate a critical role for a subtle balance of the integrin-VEGF interplay in angiogenesis and provide insight in how engineered growth factors in concert with biomaterial matrices may offer a potent molecular/material approach to harness these interactions for therapeutic angiogenesis.