The correlation between difference in foreign body reaction between implant locations and cytokine and MMP expression

Biomaterials. 2006 Dec;27(34):5763-70. doi: 10.1016/j.biomaterials.2006.07.004.


The foreign body reaction (FBR) differs between subcutaneously and supra-epicardially implanted materials. We hypothesize that this is a result of differences in cytokine, chemokine and matrix metalloproteinase (MMP) dynamics. Therefore we applied collagen disks subcutaneously and on the epicardium in mice and analyzed the FBR from day 1 to 21. Both the influx of leukocytes and implant degradation were higher in supra-epicardially implanted collagen than in subcutaneously implanted material. This correlated with a higher gene expression of pro-inflammatory cytokines such as IL-1 and IL-6, and a lower expression of the anti-inflammatory cytokine IL-10. Furthermore, the higher supra-epicardial expression of PMN attractants CXCL1/KC and CXCL2/MIP2 correlated with a higher and prolonged PMN influx. The gene expression levels of collagen degrading MMPs, i.e. MMP8, MMP13 and MMP14 were similar in subcutaneous and supra-epicardial disks. However, the activity of these enzymes was markedly higher supra-epicardially. In addition, the MMP9 expression was higher supra-epicardially, suggesting a role for this enzyme in the degradation process. In conclusion, a strong pro-inflammatory milieu is generated after supra-epicardial implantation that enables prolonged PMN presence and activation. This, together with the high supra-epicardial MMP9 level, could explain the observed difference in Col-I degradation between locations.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Cattle
  • Chemokines / genetics
  • Collagen Type I / metabolism*
  • Cytokines / genetics*
  • Extracellular Matrix / metabolism
  • Foreign-Body Reaction / genetics
  • Foreign-Body Reaction / metabolism
  • Foreign-Body Reaction / pathology*
  • Gene Expression
  • Implants, Experimental*
  • Leukocytes / immunology
  • Matrix Metalloproteinase 9 / genetics
  • Metalloendopeptidases / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Neovascularization, Pathologic / pathology
  • Pericardium / chemistry
  • Pericardium / metabolism
  • Pericardium / ultrastructure*
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • Skin / chemistry
  • Skin / metabolism
  • Skin / ultrastructure*


  • Chemokines
  • Collagen Type I
  • Cytokines
  • RNA, Messenger
  • Metalloendopeptidases
  • Matrix Metalloproteinase 9
  • Mmp9 protein, mouse