The role of collagen receptors Endo180 and DDR-2 in the foreign body reaction against non-crosslinked collagen and gelatin

Biomaterials. 2011 Feb;32(5):1339-50. doi: 10.1016/j.biomaterials.2010.09.076. Epub 2010 Nov 10.


Despite the use of collagen-derived scaffolds in regenerative medicine, little is known about the degradation mechanisms of these scaffolds in vivo. Non-crosslinked dermal sheep (NDSC) and gelatin disks were implanted subcutaneously in mice. NDSC disks showed a very low degradation rate, despite the presence of high numbers of macrophages and the influx of neutrophils. This was attributed to the presence of the matrix metalloproteinase inhibitor TIMP-1. The limited degradation occurred mainly in the later stages of the foreign body reaction, and could be attributed to (1) phagocytosis by macrophages due to a co-expression of Endo180 and MT1-MMP on these cells (intracellular degradation) and (2) the presence of MMP-13 due to an upregulation of the expression of the DDR-2 receptor (extracellular degradation). In contrast, gelatin disks degraded quickly, due to the efficient formation of large giant cells as well as the presence of MMP-13; the inhibitor TIMP-1 was absent. The DDR-2 receptor was not expressed in the gelatin disks. Endo180 and MT1-MMP were expressed, but at most times no co-expression was seen. We conclude that the physical state of collagen (native or denatured) had a dramatic outcome on the degradation rate and provoked a completely different foreign body reaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Collagen / chemistry
  • Collagen / immunology*
  • Discoidin Domain Receptors
  • Foreign-Body Reaction / immunology
  • Foreign-Body Reaction / metabolism*
  • Gelatin / chemistry
  • Gelatin / immunology*
  • Giant Cells / immunology
  • Giant Cells / metabolism
  • Immunohistochemistry
  • Macrophages / immunology
  • Macrophages / metabolism
  • Male
  • Matrix Metalloproteinase 13 / metabolism
  • Matrix Metalloproteinase 14 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Fluorescence
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptors, Mitogen / metabolism*
  • Tissue Scaffolds


  • Endo180
  • Receptors, Mitogen
  • Gelatin
  • Collagen
  • Discoidin Domain Receptors
  • Receptor Protein-Tyrosine Kinases
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase 14