Cathepsin K-sensitive poly(ethylene glycol) hydrogels for degradation in response to bone resorption.

Published

Journal Article

We propose a new strategy of biomaterial design to achieve selective cellular degradation by the incorporation of cathepsin K-degradable peptide sequences into a scaffold structure so that scaffold biodegradation can be induced at the end of the bone formation process. Poly(ethylene glycol) diacrylate (PEGDA) hydrogels were used as a model biomaterial system in this study. A cathepsin K-sensitive peptide, GGGMGPSGPWGGK (GPSG), was synthesized and modified with acryloyl-PEG-succinimidyl carbonate to produce a cross-linkable cathepsin K-sensitive polymer that can be used to form a hydrogel. Specificity of degradation of the GPSG hydrogels was tested with cathepsin K and proteinase K as a positive control, with both resulting in significant degradation compared to incubation with nonspecific collagenases over a 24-h time period. No degradation was observed when the hydrogels were incubated with plasmin or control buffers. Cell-induced degradation was evaluated by seeding differentiated MC3T3-E1 osteoblasts and RAW264.7 osteoclasts on GPSG hydrogels that were also modified with the cell adhesion peptide RGDS. Resulting surface features and resorption pits were analyzed by differential interference contrast (DIC) and fluorescent images obtained with confocal microscopy. Results from both analyses demonstrated that GPSG hydrogels can be degraded specifically in response to osteoclast attachment but not in response to osteoblasts. In summary, we have demonstrated that by incorporating a cathepsin K-sensitive peptide into a synthetic polymer structure, we can generate biomaterials that specifically respond to cues from the natural process of bone remodeling.

Full Text

Duke Authors

Cited Authors

  • Hsu, C-W; Olabisi, RM; Olmsted-Davis, EA; Davis, AR; West, JL

Published Date

  • July 2011

Published In

Volume / Issue

  • 98 / 1

Start / End Page

  • 53 - 62

PubMed ID

  • 21523904

Pubmed Central ID

  • 21523904

Electronic International Standard Serial Number (EISSN)

  • 1552-4965

International Standard Serial Number (ISSN)

  • 1549-3296

Digital Object Identifier (DOI)

  • 10.1002/jbm.a.33076

Language

  • eng