MMP-2 sensitive, VEGF-bearing bioactive hydrogels for promotion of vascular healing

D. Seliktar, A. H. Zisch, M. P. Lutolf, J. L. Wrana, J. A. Hubbel

Research output: Contribution to journalArticle

230 Citations (Scopus)

Abstract

We sought to develop bioactive hydrogels to facilitate arterial healing, e.g., after balloon angioplasty. Toward this end, we developed a new class of proteolytically sensitive, biologically active polyethylene glycol (PEG) -peptide hydrogels that can be formed in situ to temporarily protect the arterial injury from blood contact. Furthermore, we incorporated endothelial cell-specific biological signals with the goal of enhancing arterial reendothelialization. Here we demonstrate efficient endothelial cell anchorage and activation on PEG hydrogel matrices modified by conjugation with both the cell adhesive peptide motif RGD and an engineered variant of vascular endothelial growth factor (VEGF). By crosslinking peptide sequences for cleavage by MMP-2 into the polymer backbone, the hydrogels became sensitive to proteolytic degradation by cell-derived matrix metalloproteinases (MMPs). Analysis of molecular hallmarks associated with endothelial cell activation by VEGF-RGD hydrogel matrices revealed a 70% increase in production of the latent MMP-2 zymogen compared with PEG-peptide hydrogels lacking VEGF. By additional provision of transforming growth factor β1 (TGF-β1) within the PEG-peptide hydrogel, conversion of the latent MMP zymogen into its active form was demonstrated. As a result of MMP-2 activation, strongly enhanced hydrogel degradation by activated endothelial cells was observed. Our data illustrate the critical importance of growth factor activities for remodeling of synthetic biomaterials into native tissue, as it is desired in many applications of regenerative medicine. Functionalized PEG-peptide hydrogels could help restore the native vessel wall and improve the performance of angioplasty procedures.

Original languageEnglish
Pages (from-to)704-716
Number of pages13
JournalJournal of Biomedical Materials Research - Part A
Volume68
Issue number4
StatePublished - Mar 15 2004
Externally publishedYes

Fingerprint

Bearings (structural)
Hydrogels
Matrix Metalloproteinase 2
Vascular Endothelial Growth Factor A
Hydrogel
Endothelial cells
Peptides
Polyethylene glycols
Enzyme Precursors
Chemical activation
Matrix Metalloproteinases
Degradation
Balloons
Transforming Growth Factors
Biocompatible Materials
Crosslinking
Intercellular Signaling Peptides and Proteins
Metalloproteases
Adhesives
Polymers

Keywords

  • Arterial injury
  • Endothelial cells
  • Enzymatic degradation
  • Matrix metalloproteinase (MMP)
  • Polyethylene glycol

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biomaterials

Cite this

Seliktar, D., Zisch, A. H., Lutolf, M. P., Wrana, J. L., & Hubbel, J. A. (2004). MMP-2 sensitive, VEGF-bearing bioactive hydrogels for promotion of vascular healing. Journal of Biomedical Materials Research - Part A, 68(4), 704-716.

MMP-2 sensitive, VEGF-bearing bioactive hydrogels for promotion of vascular healing. / Seliktar, D.; Zisch, A. H.; Lutolf, M. P.; Wrana, J. L.; Hubbel, J. A.

In: Journal of Biomedical Materials Research - Part A, Vol. 68, No. 4, 15.03.2004, p. 704-716.

Research output: Contribution to journalArticle

Seliktar, D, Zisch, AH, Lutolf, MP, Wrana, JL & Hubbel, JA 2004, 'MMP-2 sensitive, VEGF-bearing bioactive hydrogels for promotion of vascular healing', Journal of Biomedical Materials Research - Part A, vol. 68, no. 4, pp. 704-716.
Seliktar, D. ; Zisch, A. H. ; Lutolf, M. P. ; Wrana, J. L. ; Hubbel, J. A. / MMP-2 sensitive, VEGF-bearing bioactive hydrogels for promotion of vascular healing. In: Journal of Biomedical Materials Research - Part A. 2004 ; Vol. 68, No. 4. pp. 704-716.
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