In vivo characterisation of the inflammatory reaction following mesh implantation in transgenic mice models.

INTRODUCTION: Hernia repair with prosthetic meshes represents one of the most common surgical procedures in the field of surgery. This intervention is always associated with an ensuing inflammatory response, angiogenesis and fibrotic encapsulation forming a foreign body granuloma (FBG) around the mesh fibres. Several studies have described this inflammatory reaction by characterising inflammatory cell infiltrate around the FBG after mesh explantation. However, very little is known about the real-time progression of such an inflammatory response. The aim of this study was to investigate the feasibility of monitoring the ongoing inflammatory response to mesh implantation using bioluminescence in vivo. MATERIALS AND METHODS: Three luciferase transgenic mice strains (FVB/N-Tg(Vegfr2-luc)-Xen, BALB/C-Tg(NFκB-RE-luc)-Xen and Tg(INS/EpRE-Luc)T20Rbl) were used. Mice were anaesthetized with 2 % isoflurane, and two incisions were made on the left and right sides of the abdomen of the mice. A 1-cm(2) propylene mesh was implanted subcutaneously in the right incision wound of each mouse, and the left wound served as control. Two hundred microliters of D-luciferin was injected into the mice, and bioluminescence measurements were done prior to the surgical intervention and subsequently every 3 days. After mesh explantation, histological analysis was done. Statistical analysis was done using prism GraphPad software. RESULTS: Bioluminescence results revealed different time points of maximum signal for the different mice strains. VEGFR2 gene expression peaked on day 6, NFkB on day 12 and ARE on day 3 post mesh implantation. We also observed much higher bioluminescent signal around the FBG surrounding the mesh as compared to the control wound, with p < 0.05 for all the different mice strains. CONCLUSION: Our results prove the possibility of monitoring the inflammatory reaction after mesh implantation in vivo using bioluminescence signal release. This provides a novel method of accessing and accurately describing the ongoing inflammatory response over a given period of time.

Characterisation of the cellular infiltrate in the foreign body granuloma of textile meshes with its impact on collagen deposition.

PURPOSE: As part of the foreign body reaction, mesh filaments are surrounded by an infiltrate of inflammatory cells. Though macrophages are considered as being predominant, little is known about the origin of other cells. METHODS: On 55 meshes explanted from humans, we characterised the cells in the inflammatory infiltrate of the granuloma by immunohistochemistry using 10 cellular markers: CD3+ lymphocytes, CD4+ T helper cells, CD8+ cytotoxic T cells, CD20+ B lymphocytes, CD34+ stem cells, CD45R0+ leucocytes, CD68+ macrophages, Mib1 for proliferation, Vimentin for mesenchymal origin, and Desmin for myocytes. Collagen deposits were analysed after staining with Sirius Red. RESULTS: More than 80 % of the cells in the infiltrate showed a positive expression of CD68, CD8, CD45R0 and Vimentin. CD4 and Desmin were seen in 30-80 % of the cells, unaffected by material or time. A score summarising the expression of all markers positively correlated significantly with an increased percentage of collagen type III (green) in the mesh wound. The analysis of collagen deposits was only affected to a small degree by size of area for investigation. CONCLUSIONS: At the vicinity of the mesh filaments, the accumulated inflammatory cells represent a mixture of cells of various origins. The high expression of at least four markers requires co-expression of different surface markers and thus confirms the existence of multiple transition forms instead of dominance of just macrophages. This offers new options for interventions to attenuate the inflammatory reaction of mesh implants.