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

Andreas H. Zisch, Steffen M. Zeisberger, Martin Ehrbar, Valentin Djonov, Cornelia C. Weber, Andrew Ziemiecki, Elena B. Pasquale, Jeffrey A. Hubbell

Research output: Contribution to journalArticle

49 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3245-3257
Number of pages13
JournalBiomaterials
Volume25
Issue number16
DOIs
StatePublished - Jul 1 2004
Externally publishedYes

Fingerprint

Ephrin-B2
Endothelial cells
Cell membranes
Fibrin
Intercellular Signaling Peptides and Proteins
Display devices
Cell Membrane
Ligands
Membranes
Eph Family Receptors
Engineering technology
Biomimetics
Endothelial Cells
Hydrogels
Chemical activation
Tissue
Proteins
Protein Engineering
Substrates
Hydrogel

Keywords

  • Biopolymer
  • Controlled delivery
  • Ephrin-B2
  • Fibrin
  • Hydrogel
  • Therapeutic angiogenesis

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering

Cite this

Engineered fibrin matrices for functional display of cell membrane-bound growth factor-like activities : Study of angiogenic signaling by ephrin-B2. / Zisch, Andreas H.; Zeisberger, Steffen M.; Ehrbar, Martin; Djonov, Valentin; Weber, Cornelia C.; Ziemiecki, Andrew; Pasquale, Elena B.; Hubbell, Jeffrey A.

In: Biomaterials, Vol. 25, No. 16, 01.07.2004, p. 3245-3257.

Research output: Contribution to journalArticle

Zisch, AH, Zeisberger, SM, Ehrbar, M, Djonov, V, Weber, CC, Ziemiecki, A, Pasquale, EB & Hubbell, JA 2004, 'Engineered fibrin matrices for functional display of cell membrane-bound growth factor-like activities: Study of angiogenic signaling by ephrin-B2', Biomaterials, vol. 25, no. 16, pp. 3245-3257. https://doi.org/10.1016/j.biomaterials.2003.10.015
Zisch, Andreas H. ; Zeisberger, Steffen M. ; Ehrbar, Martin ; Djonov, Valentin ; Weber, Cornelia C. ; Ziemiecki, Andrew ; Pasquale, Elena B. ; Hubbell, Jeffrey A. / Engineered fibrin matrices for functional display of cell membrane-bound growth factor-like activities : Study of angiogenic signaling by ephrin-B2. In: Biomaterials. 2004 ; Vol. 25, No. 16. pp. 3245-3257.
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