Enzymatic formation of modular cell-instructive fibrin analogs for tissue engineering

Martin Ehrbar, Simone C. Rizzi, Ruslan Hlushchuk, Valentin Djonov, Andreas H. Zisch, Jeffrey A. Hubbell, Franz E. Weber, Matthias P. Lutolf

Research output: Contribution to journalArticle

156 Citations (Scopus)

Abstract

The molecular engineering of cell-instructive artificial extracellular matrices is a powerful means to control cell behavior and enable complex processes of tissue formation and regeneration. This work reports on a novel method to produce such smart biomaterials by recapitulating the crosslinking chemistry and the biomolecular characteristics of the biopolymer fibrin in a synthetic analog. We use activated coagulation transglutaminase factor XIIIa for site-specific coupling of cell adhesion ligands and engineered growth factor proteins to multiarm poly(ethylene glycol) macromers that simultaneously form proteolytically sensitive hydrogel networks in the same enzyme-catalyzed reaction. Growth factor proteins are quantitatively incorporated and released upon cell-derived proteolytic degradation of the gels. Primary stromal cells can invade and proteolytically remodel these networks both in an in vitro and in vivo setting. The synthetic ease and potential to engineer their physicochemical and bioactive characteristics makes these hybrid networks true alternatives for fibrin as provisional drug delivery platforms in tissue engineering.

Original languageEnglish
Pages (from-to)3856-3866
Number of pages11
JournalBiomaterials
Volume28
Issue number26
DOIs
StatePublished - Sep 1 2007
Externally publishedYes

Fingerprint

Tissue Engineering
Fibrin
Tissue engineering
Intercellular Signaling Peptides and Proteins
Cells
Factor XIIIa
Cell Engineering
Artificial Cells
Proteins
Biopolymers
Behavior Control
Transglutaminases
Blood Coagulation Factors
Ethylene Glycol
Hydrogel
Cell adhesion
Biocompatible Materials
Stromal Cells
Coagulation
Drug delivery

Keywords

  • Biomimetic material
  • ECM
  • Fibrin
  • Growth factor
  • Hydrogel
  • Polyethylene glycol

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering

Cite this

Ehrbar, M., Rizzi, S. C., Hlushchuk, R., Djonov, V., Zisch, A. H., Hubbell, J. A., ... Lutolf, M. P. (2007). Enzymatic formation of modular cell-instructive fibrin analogs for tissue engineering. Biomaterials, 28(26), 3856-3866. https://doi.org/10.1016/j.biomaterials.2007.03.027

Enzymatic formation of modular cell-instructive fibrin analogs for tissue engineering. / Ehrbar, Martin; Rizzi, Simone C.; Hlushchuk, Ruslan; Djonov, Valentin; Zisch, Andreas H.; Hubbell, Jeffrey A.; Weber, Franz E.; Lutolf, Matthias P.

In: Biomaterials, Vol. 28, No. 26, 01.09.2007, p. 3856-3866.

Research output: Contribution to journalArticle

Ehrbar, M, Rizzi, SC, Hlushchuk, R, Djonov, V, Zisch, AH, Hubbell, JA, Weber, FE & Lutolf, MP 2007, 'Enzymatic formation of modular cell-instructive fibrin analogs for tissue engineering', Biomaterials, vol. 28, no. 26, pp. 3856-3866. https://doi.org/10.1016/j.biomaterials.2007.03.027
Ehrbar M, Rizzi SC, Hlushchuk R, Djonov V, Zisch AH, Hubbell JA et al. Enzymatic formation of modular cell-instructive fibrin analogs for tissue engineering. Biomaterials. 2007 Sep 1;28(26):3856-3866. https://doi.org/10.1016/j.biomaterials.2007.03.027
Ehrbar, Martin ; Rizzi, Simone C. ; Hlushchuk, Ruslan ; Djonov, Valentin ; Zisch, Andreas H. ; Hubbell, Jeffrey A. ; Weber, Franz E. ; Lutolf, Matthias P. / Enzymatic formation of modular cell-instructive fibrin analogs for tissue engineering. In: Biomaterials. 2007 ; Vol. 28, No. 26. pp. 3856-3866.
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