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

• Published in: Biomaterials 2006-12, Vol.27 (34), p.5763-5770
• Main Authors: Luttikhuizen, Daniel T., van Amerongen, Machteld J., de Feijter, Pieter C., Petersen, Arjen H., Harmsen, Martin C., van Luyn, Marja J.A.
• Format: Article
• Language: English
• Subjects: Animals; Cattle; Chemokines - genetics; Collagen; Collagen Type I - metabolism; Cytokine; Cytokines - genetics; Extracellular Matrix - metabolism; Foreign-Body Reaction - genetics; Foreign-Body Reaction - metabolism; Foreign-Body Reaction - pathology; Gene Expression; Implants, Experimental; Inflammation; Leukocytes - immunology; Matrix metalloproteinase; Matrix Metalloproteinase 9 - genetics; Metalloendopeptidases - genetics; Mice; Mice, Inbred C57BL; Neovascularization, Pathologic - pathology; Pericardium - chemistry; Pericardium - metabolism; Pericardium - ultrastructure; Rat; RNA, Messenger - analysis; RNA, Messenger - metabolism; Skin - chemistry; Skin - metabolism; Skin - ultrastructure
• ISSN: 0142-9612; 1878-5905
• 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.