SPARC-derived protease substrates to enhance the plasmin sensitivity of molecularly engineered PEG hydrogels

J. Patterson, J. A. Hubbell

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Bioactive hydrogels formed from the Michael-type addition reactions of end-functionalized poly (ethylene glycol) macromers with thiol-containing protease-sensitive peptide crosslinkers have previously been described as matrices for cell-induced enzymatic remodeling. In this study, we sought to develop materials formulations with different degradation profiles by evaluating peptides derived from secreted protein acidic and rich in cysteine (SPARC) as potential substrates for plasmin, matrix metalloproteinase (MMP)-1, and MMP-2. Michaelis-Menten analysis showed that different peptides could provide a range of kcat values for each enzyme. In most cases, hydrogels formed with crosslinker peptides that had higher kcat values degraded faster when exposed to the appropriate enzyme(s), and fibroblasts showed increased cell proliferation and cell spreading when cultured in the faster degrading hydrogels. Further, greater cell invasion was observed from aortic ring segments embedded in the faster degrading hydrogels. The addition of the SPARC-derived peptides to the repertoire of protease-sensitive crosslinkers increases the potential application of these materials by providing enhanced susceptibility to plasmin. Further, the graded increases in kcat and the differential responses for plasmin, MMP-1, and MMP-2 can be used to engineer hydrogels with degradation properties tuned to the enzymes produced by particular cell types, allowing for broader in vivo application.

Original languageEnglish (US)
Pages (from-to)1301-1310
Number of pages10
JournalBiomaterials
Volume32
Issue number5
DOIs
StatePublished - Feb 1 2011

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Keywords

  • Biodegradation
  • Biomimetic material
  • Cell spreading
  • Hydrogel
  • Matrix metalloproteinase
  • Peptide

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

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