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Engineered fibrin matrices for functional display of cell membrane-bound growth factor-like activities: Study of angiogenic signaling by ephrin-B2

Paper ID Volume ID Publish Year Pages File Format Full-Text
12426 792 2004 13 PDF Available
Title
Engineered fibrin matrices for functional display of cell membrane-bound growth factor-like activities: Study of angiogenic signaling by ephrin-B2
Abstract

With the rapid increase in approaches to pro- or anti-angiogenic therapy, new and effective methodologies for administration of cell-bound growth factors will be required. We sought to develop the natural hydrogel matrix fibrin as platform for extensive interactions and continuous signaling by the vascular morphogen ephrin-B2 that normally resides in the plasma membrane and requires multivalent presentation for ligation and activation of Eph receptors on apposing endothelial cell surfaces. Using fibrin and protein engineering technology to induce multivalent ligand presentation, a recombinant mutant ephrin-B2 receptor binding domain was covalently coupled to fibrin networks at variably high densities. The ability of fibrin-bound ephrin-B2 to act as ligand for endothelial cells was preserved, as demonstrated by a concomitant, dose-dependent increase of endothelial cell binding to engineered ephrin-B2–fibrin substrates in vitro. The therapeutic relevance of ephrin-B2–fibrin implant matrices was demonstrated by a local angiogenic response in the chick embryo chorioallontoic membrane evoked by the local and prolonged presentation of matrix-bound ephrin-B2 to tissue adjacing the implant.This new knowledge on biomimetic fibrin vehicles for precise local delivery of membrane-bound growth factor signals may help to elucidate specific biological growth factor function, and serve as starting point for development of new treatment strategies.

Keywords
Ephrin-B2; Therapeutic angiogenesis; Fibrin; Hydrogel; Controlled delivery; Biopolymer
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Engineered fibrin matrices for functional display of cell membrane-bound growth factor-like activities: Study of angiogenic signaling by ephrin-B2
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 25, Issue 16, July 2004, Pages 3245–3257
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us