Host response to sponge implants differs between subcutaneous and intraperitoneal sites in mice

Abstract

Synthetic matrices have been used widely to repair and/or to replace biological tissues. However, there is relatively little information on the effect of different anatomical compartments on the host response to foreign implants. We have analyzed such responses to sponge implants in subcutaneous and in intraperitoneal sites in mice at days 3, 5, and 8 postimplantation by measuring inflammation, angiogenesis, and production of proangiogenic/inflammatory cytokines. The angiogenic response, assessed by hemoglobin content and by morphometric analysis of the number of vessels, was higher in intraperitoneal implants. Levels of vascular endothelial growth factor in intraperitoneal implants were 14-fold higher than in subcutaneous implants at day 3 and remained high for the next 5 days. Neutrophil accumulation as determined by myeloperoxidase activity was the same in both types of implants. Macrophage accumulation (N-acetylglucosaminidase activity) was also similar on days 3 and 8 in both implants. Levels of the chemokine CXCL2/KC were always higher, but those of CCL2/JE lower, in the intraperitoneal implant. These results demonstrate that the anatomical site of the implant markedly influenced the host response to synthetic matrices. Our results provide a greater understanding of factors affecting the biocompatibility of exogenous materials placed at different anatomical sites.

Brazilian green propolis modulates inflammation, angiogenesis and fibrogenesis in intraperitoneal implant in mice

“…It is intriguing that the reported anti-inflammatory effects of propolis are in contrast with the results presented here, particularly those from our group, which showed propolis to exert an anti-inflammatory effect on implants located subcutaneously in mice [16]. We have previously demonstrated that the anatomical site markedly influences the host response to a synthetic matrix [19] and, herein, we extend this observation to the host response to a pharmacological compound. It is striking that by up-regulating pro-inflammatory pathways, propolis has down-regulated angiogenesis and fibrosis in the peritoneal implant.…”

Cilostazol and pentoxifylline decrease angiogenesis, inflammation, and fibrosis in sponge-induced intraperitoneal adhesion in mice

“…The intraperitoneal implants were shown to be extensively adhered to other organs (liver, intestines), highly vascularized, infiltrated with inflammatory cells, fibroblast-and mesothelial-like cells, and to produce pro-inflammatory and proangiogenic cytokines (Mendes et al 2007). In this study, we used this murine model of peritoneal adhesion to investigate the effects of controlling adhesion development through inhibition of its key components (angiogenesis, inflammation and fibrosis) with the PDE inhibitors cilostazol and PTX.…”

“…We recently reported that implantation of synthetic matrix in the peritoneal cavity of mice elicited the formation of adhesions whose components angiogenesis, inflammation, and fibrosis (common features of human adhesions and of experimental animal models) were identified. In this model, we were able to assess many parameters of the newly induced fibrovascular tissue, including the formation of new blood vessels, the levels of inflammatory and angiogenic cytokines, and the infiltration of leukocytes (Mendes et al 2007).…”

Foreign Body Response to Subcutaneous Implants in Diabetic Rats

“…The extent of mononuclear cells in the sponge implants was quantitated by measuring the levels of the lysosomal enzyme, N-acetyl-glucosaminidase (NAG), present in high levels in activated macrophages [12], [15]–[16]. The implants were homogenized in 2 mL NaCl solution (0.9% w/v) containing 0.1% v/v Triton X-100 (Promega, Madison, WI) and centrifuged at 3000 rpm; 10 min at 4°C.…”