Recombinant protein-co-PEG networks as cell-adhesive and proteolytically degradable hydrogel matrixes. Part II: Biofunctional characteristics

Simon C. Rizzi, Martin Ehrbar, Sven Halstenberg, George P. Raeber, Hugo G. Schmoekel, Henri Hagenmüller, Ralph Müller, Franz E. Weber, Jeffrey A. Hubbell, Jeffrey A. Hubbell

Research output: Contribution to journalArticle

148 Citations (Scopus)

Abstract

We present here the biological performance in supporting tissue regeneration of hybrid hydrogels consisting of genetically engineered protein polymers that carry specific features of the natural extracellular matrix, cross-linked with reactive poly(ethylene glycol) (PEG). Specifically, the protein polymers contain the cell adhesion motif RGD, which mediates integrin receptor binding, and degradation sites for plasmin and matrix-metalloproteinases, both being proteases implicated in natural matrix remodeling. Biochemical assays as well as in vitro cell culture experiments confirmed the ability of these protein-PEG hydrogels to promote specific cellular adhesion and to exhibit degradability by the target enzymes. Cell culture experiments demonstrated that proteolytic sensitivity and suitable mechanical properties were critical for three-dimensional cell migration inside these synthetic matrixes. In vivo, protein-PEG matrixes were tested as a carrier of bone morphogenetic protein (rhBMP-2) to heal critical-sized defects in a rat calvarial defect model. The results underscore the importance of fine-tuning material properties of provisional therapeutic matrixes to induce cellular responses conducive to tissue repair. In particular, a lack of rhBMP or insufficient degradability of the protein-PEG matrix prevented healing of bone defects or remodeling and replacement of the artificial matrix. This work confirms the feasibility of attaining desired biological responses in vivo by engineering material properties through the design of single components at the molecular level. The combination of polymer science and recombinant DNA technology emerges as a powerful tool for the development of novel biomaterials.

Original languageEnglish
Pages (from-to)3019-3029
Number of pages11
JournalBiomacromolecules
Volume7
Issue number11
DOIs
StatePublished - Nov 1 2006
Externally publishedYes

Fingerprint

Recombinant proteins
Hydrogel
Recombinant Proteins
Hydrogels
Adhesives
Polyethylene glycols
Proteins
Polymers
Cell culture
Defects
Materials properties
Cell Culture Techniques
Bone
Genetic engineering
Bone Morphogenetic Protein 2
Tissue regeneration
Bone Morphogenetic Proteins
Recombinant DNA
Ethylene Glycol
Fibrinolysin

ASJC Scopus subject areas

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

Cite this

Rizzi, S. C., Ehrbar, M., Halstenberg, S., Raeber, G. P., Schmoekel, H. G., Hagenmüller, H., ... Hubbell, J. A. (2006). Recombinant protein-co-PEG networks as cell-adhesive and proteolytically degradable hydrogel matrixes. Part II: Biofunctional characteristics. Biomacromolecules, 7(11), 3019-3029. https://doi.org/10.1021/bm060504a

Recombinant protein-co-PEG networks as cell-adhesive and proteolytically degradable hydrogel matrixes. Part II : Biofunctional characteristics. / Rizzi, Simon C.; Ehrbar, Martin; Halstenberg, Sven; Raeber, George P.; Schmoekel, Hugo G.; Hagenmüller, Henri; Müller, Ralph; Weber, Franz E.; Hubbell, Jeffrey A.; Hubbell, Jeffrey A.

In: Biomacromolecules, Vol. 7, No. 11, 01.11.2006, p. 3019-3029.

Research output: Contribution to journalArticle

Rizzi, SC, Ehrbar, M, Halstenberg, S, Raeber, GP, Schmoekel, HG, Hagenmüller, H, Müller, R, Weber, FE, Hubbell, JA & Hubbell, JA 2006, 'Recombinant protein-co-PEG networks as cell-adhesive and proteolytically degradable hydrogel matrixes. Part II: Biofunctional characteristics', Biomacromolecules, vol. 7, no. 11, pp. 3019-3029. https://doi.org/10.1021/bm060504a
Rizzi, Simon C. ; Ehrbar, Martin ; Halstenberg, Sven ; Raeber, George P. ; Schmoekel, Hugo G. ; Hagenmüller, Henri ; Müller, Ralph ; Weber, Franz E. ; Hubbell, Jeffrey A. ; Hubbell, Jeffrey A. / Recombinant protein-co-PEG networks as cell-adhesive and proteolytically degradable hydrogel matrixes. Part II : Biofunctional characteristics. In: Biomacromolecules. 2006 ; Vol. 7, No. 11. pp. 3019-3029.
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