Enzyme and cytokine effects on the impaired onset of the murine foreign-body reaction to dermal sheep collagen

J Biomed Mater Res. 2001 Feb;54(2):234-40. doi: 10.1002/1097-4636(200102)54:2<234::aid-jbm10>3.0.co;2-s.


Subcutaneous implantation of biodegradable hexamethylenediisocyanate crosslinked dermal sheep collagen (HDSC) elicited little foreign-body reaction in mice in contrast to rats. If the factor(s) resulting in this minor foreign-body reaction are better understood, this knowledge can be used to modulate unwanted foreign-body reactions. Therefore, we investigated whether the phagocytic potential of murine macrophages and giant cells could be enhanced. Disks of HDSC were predegraded with collagenase or impregnated with tumor necrosis factor-alpha (TNF-alpha) or interferon-gamma (IFN-gamma) before implantation in 129 SVEV mice. Explantation was performed on days 7, 14, 21, and 28 and the disks were evaluated at the (immuno) light and transmission electron-microscopic levels. More giant cells were present in the predegraded disks. Cells were associated with the HDSC bundles, and the onset of phagocytosis started on day 28, in contrast to the controls and the disks impregnated with the cytokines. Expression of MHC class II was minimal in all groups. The matrix metalloproteinases MMP-2 and MMP-9 were expressed in all groups although on day 28 MMP-9 expression was higher in the predegraded disks. Thus, predegradation only slightly enhanced the onset of the foreign-body reaction to HDSC in mice, and impregnation with cytokines not at all. This suggests that lack of proteolytic enzymes or TNF-alpha or IFN-gamma is not the cause of the impaired onset of the foreign-body reaction.

MeSH terms

  • Animals
  • Cell Division / drug effects
  • Clostridium / enzymology
  • Collagen / toxicity*
  • Collagenases / metabolism
  • Foreign-Body Reaction / pathology
  • Foreign-Body Reaction / physiopathology*
  • Foreign-Body Reaction / prevention & control
  • Giant Cells / drug effects
  • Giant Cells / physiology*
  • Giant Cells / ultrastructure
  • Interferon-gamma / pharmacology*
  • Macrophages / drug effects
  • Macrophages / physiology*
  • Macrophages / ultrastructure
  • Mice
  • Mice, Inbred Strains
  • Phagocytosis
  • Rats
  • Recombinant Proteins
  • Sheep
  • Skin
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Collagen
  • Collagenases