Annals of Biomedical Engineering

, Volume 37, Issue 7, pp 1368–1375

Catabolic Responses of Chondrocyte-Seeded Peptide Hydrogel to Dynamic Compression

  • John D. Kisiday
  • Jennifer H. Lee
  • Patrick N. Siparsky
  • David D. Frisbie
  • Carl R. Flannery
  • John D. Sandy
  • Alan J. Grodzinsky
Article

DOI: 10.1007/s10439-009-9699-9

Cite this article as:
Kisiday, J.D., Lee, J.H., Siparsky, P.N. et al. Ann Biomed Eng (2009) 37: 1368. doi:10.1007/s10439-009-9699-9
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Abstract

This study investigated the role of matrix metalloproteases and aggrecanases during dynamic compression-induced aggrecan catabolism in chondrocyte-seeded self-assembling peptide hydrogel. One- to two-week-old bovine chondrocytes were encapsulated into peptide hydrogel and cultured for 14 days prior to the application of an alternate day loading protocol. Dynamic compression-induced aggrecan catabolism was explored by evaluating GAG loss to the culture medium, zymography for matrix metalloproteases (MMPs), gene expression of MMPs and ADAMTS proteases, and Western blot analysis for aggrecan fragments. The application of loading over 4 days increased GAG loss to the medium three- to four-fold relative to free-swelling controls. Zymogram analysis detected increased concentrations of latent MMP-9 and MMP-3 in the culture medium relative to free-swelling culture. Real-time PCR showed expression levels of MMPs and ADAMTS proteases in loaded samples that ranged from 2.5- to 95-fold higher than free-swelling culture. Aggrecan fragment analysis did not detect small (50–80 kDa) molecular weight fragments in free-swelling culture; however, dynamic compression samples contained 60–80 kDa fragments that were detected by both anti-G1 and NITEGE probes, demonstrating ADAMTS but not MMP degradation. These data suggest that partially mature cartilage tissue engineering constructs may be susceptible to catabolic degradation.

Keywords

Cartilage tissue engineering Aggrecan catabolism Chondrocyte mechanotransduction 

Copyright information

© Biomedical Engineering Society 2009

Authors and Affiliations

  • John D. Kisiday
    • 1
    • 5
  • Jennifer H. Lee
    • 1
  • Patrick N. Siparsky
    • 4
  • David D. Frisbie
    • 5
  • Carl R. Flannery
    • 6
  • John D. Sandy
    • 7
  • Alan J. Grodzinsky
    • 1
    • 2
    • 3
    • 4
  1. 1.Department of Biological EngineeringMassachusetts Institute of TechnologyCambridgeUSA
  2. 2.Department of Mechanical EngineeringMassachusetts Institute of TechnologyCambridgeUSA
  3. 3.Department of Electrical EngineeringMassachusetts Institute of TechnologyCambridgeUSA
  4. 4.Center for Biomedical EngineeringMassachusetts Institute of TechnologyCambridgeUSA
  5. 5.Department of Clinical Science, Orthopaedic Research CenterColorado State UniversityFort CollinsUSA
  6. 6.Wyeth ResearchCambridgeUSA
  7. 7.Department of BiochemistryRush Medical SchoolChicagoUSA

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