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MMP levels in the response to degradable implants in the presence of a hydroxamate‐based matrix metalloproteinase sequestering biomaterial in vivo
Author(s) -
Khan Omar F.,
JeanFrancois Jacques,
Sefton Michael V.
Publication year - 2009
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.32634
Subject(s) - in vivo , biomaterial , gelatin , matrix metalloproteinase , extracellular matrix , materials science , implant , biomedical engineering , biophysics , matrix (chemical analysis) , in vitro , chemistry , biochemistry , nanotechnology , biology , surgery , medicine , composite material , microbiology and biotechnology
The inflammatory response to an implanted tissue engineered construct alters the remodeling that occurs and this can diminish the intended therapeutic effect. It was hypothesized that the use of a hydroxamate‐based matrix metalloproteinase (MMP) sequestering biomaterial (MI) in the form of ∼200 μm microspheres would lower the amount and activity of MMP in vivo in response to a subcutaneous, degradable implant (gelatin or Integra® disc). MMP degrade extracellular matrix, facilitating inflammatory cell migration and local remodeling of the implant environment. Gelatin or Integra® discs were implanted subcutaneously in the backs of CD1 mice together with 30 mg of MI microspheres or with 30 mg of similarly sized control poly(methyl methacrylate) (PMMA) microspheres in a paired study. To sample the implant space, weakly adsorbed protein or attached cells were recovered from explanted discs by soaking the discs in PBS overnight at 4°C. Unexpectedly, MMP‐2, ‐8, ‐9, and TIMP‐1 levels were surprisingly similar in this recovered fluid for the two treatments. Also, there were significantly more (and at day 4 an order of magnitude more) leukocytes recovered from the gelatin discs coimplanted with the MI microspheres than with the PMMA control. It is suggested that the MI microspheres disturbed the natural MMP control pathway leading to high‐leukocyte numbers, especially at early times. These results highlight the challenge associated with controlling the fate of tissue engineered constructs in vivo . © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010