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

Ye, Qingsong, Harmsen, Martin C., Ren, Yijin, and Bank, Ruud A. (2011) The role of collagen receptors Endo180 and DDR-2 in the foreign body reaction against non-crosslinked collagen and gelatin. Biomaterials, 32 (5). pp. 1339-1350.

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Abstract

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.

Item ID: 16240
Item Type: Article (Research - C1)
ISSN: 1878-5905
Keywords: collagen; gelatin; Endo180; DDR-2; foreign body reaction; giant cells
Date Deposited: 09 Jun 2011 07:12
FoR Codes: 09 ENGINEERING > 0903 Biomedical Engineering > 090301 Biomaterials @ 60%
11 MEDICAL AND HEALTH SCIENCES > 1199 Other Medical and Health Sciences > 119999 Medical and Health Sciences not elsewhere classified @ 40%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920199 Clinical Health (Organs, Diseases and Abnormal Conditions) not elsewhere classified @ 100%
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