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, Jeffrey A. Hubbell

Research output: Contribution to journalArticle

262 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)710-723
Number of pages14
JournalBiomacromolecules
Volume3
Issue number4
DOIs
StatePublished - Aug 29 2002
Externally publishedYes

Fingerprint

Hydrogels
Ethylene Glycol
Fibrinolysin
Grafts
Adhesives
Polyethylene glycols
Repair
Tissue
Proteins
Transplants
Integrins
Tissue regeneration
Thrombin
Wound Healing
Fibrinogen
Heparin
Regeneration
Biomimetic Materials
Biomimetic materials
Protein Precursors

ASJC Scopus subject areas

  • Organic Chemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Polymers and Plastics
  • Materials Chemistry

Cite this

Biologically engineered protein-graft-poly(ethylene glycol) hydrogels : A cell adhesive and plasmin-degradable biosynthetic material for tissue repair. / Halstenberg, Sven; Panitch, Alyssa; Rizzi, Simone; Hall, Heike; Hubbell, Jeffrey A.

In: Biomacromolecules, Vol. 3, No. 4, 29.08.2002, p. 710-723.

Research output: Contribution to journalArticle

Halstenberg, Sven ; Panitch, Alyssa ; Rizzi, Simone ; Hall, Heike ; Hubbell, Jeffrey A. / Biologically engineered protein-graft-poly(ethylene glycol) hydrogels : A cell adhesive and plasmin-degradable biosynthetic material for tissue repair. In: Biomacromolecules. 2002 ; Vol. 3, No. 4. pp. 710-723.
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