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Physical matrices stabilized by enzymatically sensitive covalent crosslinks.

Abstract
This work describes a unique system of gel and gel-like materials formed from physical bonds between heparin and heparin binding peptides (dG-PBD) coupled to multivalent poly(ethylene glycol) vinyl sulfone star polymers (PEGVS) and formed from covalent bonds between an enzymatically sensitive crosslinker and PEGVS. Dynamic mechanical testing revealed that the viscoelastic behavior and gelation kinetics of 10% (w/v) gels formed from 2:1 dG-PBD:PEGVS, heparin, and crosslinker (2:1 gels) and from 3:1 dG-PBD:PEGVS, heparin, and crosslinker (3:1 materials) were significantly influenced by the presence of both physical and covalent bonds. Furthermore, the mechanical properties of both compositions were thermally responsive and reversible. At 4 degrees C, the storage modulus, G', for 2:1 gels (5005.3+/-592.0Pa) and 3:1 materials (5512.0+/-272.7Pa) were statistically similar; however, at 45 degrees C, G' of 2:1 gels decreased to 477.9+/-150.4Pa, and the viscoelastic behavior of 3:1 materials was dominated by viscous behavior. In addition, the mechanical properties of 2:1 gels and 3:1 materials were sensitive to the frequency of the applied stress at 4 degrees C, 20 degrees C, and at 37 degrees C. Although the covalent bonds within the materials provided mechanical stability, the overall viscoelastic response of this system could be dominated by physical crosslinks under certain conditions. Results from degradation studies indicated that the crosslinker was sensitive to collagenase type I but not to thrombin or heparinase I, and a hemolysis assay suggested that the 2:1 gels and 3:1 materials might be biocompatible. These materials could be useful to study the role of physical interactions within networks that mimic the extracellular matrix.
AuthorsBrandon L Seal, Alyssa Panitch
JournalActa biomaterialia (Acta Biomater) Vol. 2 Issue 3 Pg. 241-51 (May 2006) ISSN: 1742-7061 [Print] England
PMID16701884 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Biocompatible Materials
  • Cross-Linking Reagents
  • Gels
  • Peptides
  • Polyethylene Glycols
  • Heparin
Topics
  • Amino Acid Sequence
  • Biocompatible Materials
  • Cross-Linking Reagents (chemistry, metabolism)
  • Elasticity
  • Gels
  • Heparin
  • Kinetics
  • Models, Molecular
  • Molecular Sequence Data
  • Peptides (chemical synthesis, chemistry)
  • Polyethylene Glycols (chemistry)
  • Viscosity

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