Tissue remodeling macrophages morphologically dominate at the interface of polypropylene surgical meshes in the human abdomen

A Dievernich,U Klinge,L Davies,P Achenbach

doi:10.1007/s10029-020-02315-2

A Dievernich, U Klinge + Show 2 more

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https://doi.org/10.1007/s10029-020-02315-2

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Abstract

BackgroundMesh implants are widely used to reinforce the abdominal wall, although the inevitable inflammatory foreign body reaction (FBR) at the interface leads to complications. Macrophages are suspected to regulate the subsequent scar formation, but it is still unclear whether adequate fibrous scar formation with collagen deposition depends mainly on the presence of M1 or M2 macrophages.MethodsThis study investigated the FBR to seven human polypropylene meshes, which were removed after a median incorporation time of 1 year due to the primary complaint of recurrence. Using immunofluorescence, the FBR was examined in six regional zones with increasing distance from the mesh fibers up to 350 µm, based on the cell densities, macrophage M1 (CD86) and M2 (CD163, CD206) phenotypes, deposition of collagen-I and -III, and expression of matrix metalloproteinase-2 (MMP-2) and -8 as indicator of collagen degradation.ResultsAll mesh–tissue complexes demonstrated a decrease in cell density and macrophages with distance to the mesh fibers. Overall, about 60% of the macrophages presented an M2 phenotype, whereas only 6% an M1 phenotype. Over 70% of macrophages showed co-expression with collagen-I or -III and over 50% with MMP-2.ConclusionsThe chronic FBR to polypropylene meshes is associated with an M2 macrophage response, which is accompanied by collagen deposition and MMP-2 expression. These findings challenge the idea that mainly M1 macrophages are related to inflammation and highlights that iatrogenic attempts to polarize these cells towards the M2 phenotype may not be a solution to ameliorate the long-term foreign body reaction.

Highlights

Textile mesh structures made of polypropylene are widely used to reinforce a hernia repair in the abdominal wall
By relating the collagen areas in each regional zone to the respective number of all cells, we found that the average collagen area per cell for both collagens increased with increasing distance from the mesh fibers (Fig. 10)
The examination of the spatial morphology of the macrophages at the foreign body granuloma around meshes by combining a custom Euclidean distance map algorithm with immunofluorescence staining of entire tissue sections of polypropylene (PP) mesh explants demonstrated that cell density and macrophage ratio decreased with distance to the PP fibers, and that these were predominantly M2 macrophages

Summary

Introduction

Textile mesh structures made of polypropylene are widely used to reinforce a hernia repair in the abdominal wall. In 1992, Stein et al demonstrated that IL-4 is an alternative activator for macrophages [2] His findings later led to the separation of activated macrophages into two main populations, designated classically activated (M1) and alternatively activated (M2) [3]. Mesh implants are widely used to reinforce the abdominal wall, the inevitable inflammatory foreign body reaction (FBR) at the interface leads to complications. Conclusions The chronic FBR to polypropylene meshes is associated with an M2 macrophage response, which is accompanied by collagen deposition and MMP-2 expression. These findings challenge the idea that mainly M1 macrophages are related to inflammation and highlights that iatrogenic attempts to polarize these cells towards the M2 phenotype may not be a solution to ameliorate the long-term foreign body reaction

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