Synthetic matrix metalloproteinase-sensitive hydrogels for the conduction of tissue regeneration: Engineering cell-invasion characteristics

M. P. Lutolf, J. L. Lauer-Fields, H. G. Schmoekel, A. T. Metters, F. E. Weber, G. B. Fields, J. A. Hubbell

Research output: Contribution to journalArticle

989 Citations (Scopus)

Abstract

Synthetic hydrogels have been molecularly engineered to mimic the invasive characteristics of native provisional extracellular matrices: a combination of integrin-binding sites and substrates for matrix metalloproteinases (MMP) was required to render the networks degradable and invasive by cells via cell-secreted MMPs. Degradation of gels was engineered starting from a characterization of the degradation kinetics (kcat and Km) of synthetic MMP substrates in the soluble form and after crosslinking into a 3D hydrogel network. Primary human fibroblasts were demonstrated to proteolytically invade these networks, a process that depended on MMP substrate activity, adhesion ligand concentration, and network crosslinking density. Gels used to deliver recombinant human bone morphogenetic protein-2 to the site of critical defects in rat cranium were completely infiltrated by cells and remodeled into bony tissue within 4 wk at a dose of 5 μg per defect. Bone regeneration was also shown to depend on the proteolytic sensitivity of the matrices. These hydrogels may be useful in tissue engineering and cell biology as alternatives for naturally occurring extracellular matrix-derived materials such as fibrin or collagen.

Original languageEnglish
Pages (from-to)5413-5418
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number9
DOIs
StatePublished - Apr 29 2003
Externally publishedYes

Fingerprint

Hydrogels
Tissue Engineering
Matrix Metalloproteinases
Regeneration
Extracellular Matrix
Gels
Bone Regeneration
Hydrogel
Fibrin
Skull
Integrins
Cell Biology
Collagen
Fibroblasts
Binding Sites
Ligands

Keywords

  • Biomaterials
  • Extracellular matrix
  • Proteolytic degradation

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Synthetic matrix metalloproteinase-sensitive hydrogels for the conduction of tissue regeneration : Engineering cell-invasion characteristics. / Lutolf, M. P.; Lauer-Fields, J. L.; Schmoekel, H. G.; Metters, A. T.; Weber, F. E.; Fields, G. B.; Hubbell, J. A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. 9, 29.04.2003, p. 5413-5418.

Research output: Contribution to journalArticle

Lutolf, M. P. ; Lauer-Fields, J. L. ; Schmoekel, H. G. ; Metters, A. T. ; Weber, F. E. ; Fields, G. B. ; Hubbell, J. A. / Synthetic matrix metalloproteinase-sensitive hydrogels for the conduction of tissue regeneration : Engineering cell-invasion characteristics. In: Proceedings of the National Academy of Sciences of the United States of America. 2003 ; Vol. 100, No. 9. pp. 5413-5418.
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