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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. (2007) Enzymatic formation of modular cell-instructive fibrin analogs for tissue engineering. Biomaterials, 28(26), pp. 3856-3866.

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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.

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63 citations in Web of Science®

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ID Code: 12974
Item Type: Journal Article
Additional Information: For more information, please refer to the journal's website (see hypertext link) or contact the author.
Keywords: ECM, Fibrin, Hydrogel, Biomimetic material, Polyethylene glycol, Growth factor
DOI: 10.1016/j.biomaterials.2007.03.027
ISSN: 0142-9612
Subjects: Australian and New Zealand Standard Research Classification > TECHNOLOGY (100000) > MEDICAL BIOTECHNOLOGY (100400) > Medical Biotechnology not elsewhere classified (100499)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > MEDICAL PHYSIOLOGY (111600) > Cell Physiology (111601)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > MEDICAL BIOCHEMISTRY AND METABOLOMICS (110100) > Medical Biochemistry and Metabolomics not elsewhere classified (110199)
Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > BIOCHEMISTRY AND CELL BIOLOGY (060100) > Biochemistry and Cell Biology not elsewhere classified (060199)
Divisions: Past > QUT Faculties & Divisions > Faculty of Science and Technology
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2007 Elsevier
Deposited On: 11 Mar 2008
Last Modified: 29 Feb 2012 23:40

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