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Biologically Engineered Protein-graft-Poly(ethylene glycol) Hydrogels: A Cell Adhesive and Plasmin-Degradable Biosynthetic Material for Tissue Repair

Halstenberg, Sven and Panitch, Alyssa and Rizzi, Simone and Hall, Heike and Hubbell, Jeffrey A. (2002) Biologically Engineered Protein-graft-Poly(ethylene glycol) Hydrogels: A Cell Adhesive and Plasmin-Degradable Biosynthetic Material for Tissue Repair. Biomacromolecules, 3 (4). pp. 710-723. ISSN 1525-7797. doi:10.1021/bm015629o. https://resolver.caltech.edu/CaltechAUTHORS:20170201-093516947

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Abstract

To address the need for bioactive materials toward clinical applications in wound healing and tissue regeneration, an artificial protein was created by recombinant DNA methods and modified by grafting of poly(ethylene glycol) diacrylate. Subsequent photopolymerization of the acrylate-containing precursors yielded protein-graft-poly(ethylene glycol) hydrogels. The artificial protein contained repeating amino acid sequences based on fibrinogen and anti-thrombin III, comprising an RGD integrin-binding motif, two plasmin degradation sites, and a heparin-binding site. Two-dimensional adhesion studies showed that the artificial protein had specific integrin-binding capability based on the RGD motif contained in its fibrinogen-based sequence. Furthermore, heparin bound strongly to the protein's anti-thrombin III-based region. Protein-graft-poly(ethylene glycol) hydrogels were plasmin degradable, had Young's moduli up to 3.5 kPa, and supported three-dimensional outgrowth of human fibroblasts. Cell attachment in three dimensions resulted from specific cell-surface integrin binding to the material's RGD sequence. Hydrogel penetration by cells involved serine-protease mediated matrix degradation in temporal and spatial synchrony with cellular outgrowth. Protein-graft-poly(ethylene glycol) hydrogels represent a new and versatile class of biomimetic hybrid materials that hold clinical promise in serving as implants to promote wound healing and tissue regeneration.


Item Type:Article
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URLURL TypeDescription
http://dx.doi.org/10.1021/bm015629oDOIArticle
http://pubs.acs.org/doi/abs/10.1021/bm015629oPublisherArticle
Additional Information:© 2002 American Chemical Society. Received 22 October 2001. Published online 16 May 2002. Published in print 1 July 2002. We thank Ragna Sack of the Protein Analysis Unit, Department of Biochemistry, University of Zurich, for the amino acid analyses; Ronald Schoenmakers of the Institute for Biomedical Engineering, ETH and University of Zurich, for helpful discussions of this work; Dror Seliktar of the Institute for Biomedical Engineering, ETH and University of Zurich, for the didansyl oligopeptide; and Anita Saraf of Northwestern University, USA, for help with the rheological measurements.
Issue or Number:4
DOI:10.1021/bm015629o
Record Number:CaltechAUTHORS:20170201-093516947
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170201-093516947
Official Citation:Biologically Engineered Protein-graft-Poly(ethylene glycol) Hydrogels:  A Cell Adhesive and Plasmin-Degradable Biosynthetic Material for Tissue Repair Sven Halstenberg, Alyssa Panitch, Simone Rizzi, Heike Hall, and Jeffrey A. Hubbell Biomacromolecules 2002 3 (4), 710-723 DOI: 10.1021/bm015629o
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:73918
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:01 Feb 2017 17:58
Last Modified:11 Nov 2021 05:23

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