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

Abstract

Background Mesh 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. Methods This 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. Results All 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. 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.

Characterization of innate and adaptive immune cells involved in the foreign body reaction to polypropylene meshes in the human abdomen

“…The data are presented as mean (SE). Significant differences between zones according to Mann-Whitney U test: a zone1 and zone2, b zone1 and zone6 Parameter (n = 7 PP meshes) Distance from mesh fibers previous studies of the same specimens that clearly showed excessive collagen deposition [20], may suggest T regs are not antifibrotic in our samples. Within the FBGs, CD20 + B cells were rare at about 5%, which is in agreement with several studies [4,23,27], but interestingly dense clusters were frequently found near the FBGs accumulated around blood vessels.…”

Quantitative Characterization of Macrophage, Lymphocyte, and Neutrophil Subtypes Within the Foreign Body Granuloma of Human Mesh Explants by 5-Marker Multiplex Fluorescence Microscopy

“…As already indicated by the previous work of Dievernich et al using double stainings, only a minority of cells that just expressed a single marker can be assigned to a specific cell type ( 1 ). As we restricted the analyses just to the inflammatory infiltrate of the granuloma in this study, we did not look for spatial gradients.…”

“…Macrophages have been shown to be the predominant actors of the chronic inflammation around these foreign bodies, with some of them fusing to multinucleated foreign body giant cells (FBGCs) ( Supplementary Figure 1A in Supplementary Material 1 ). Characteristic surface markers are CD68 as pan-macrophage marker, CD86 for M1 subtype, CD105 indicates macrophage activation, and CD163 and also CD206 reflect M2 subtypes ( 1 ). Though these subtypes appear with distinct spatial distribution, they all can be found within a FBG.…”

Analysis of tissue inflammatory response, fibroplasia, and foreign body reaction between the polyglactin suture of abdominal aponeurosis in rats and the intraperitoneal implant of polypropylene, polypropylene/polyglecaprone and polyester/porcine collagen meshes

“…However, the results of the present study and those of Gruber-Blum et al . 24 did not show significant differences between groups with or without an anti-adhesive barrier in relation to the intensity of the foreign body reaction, although there was a greater tendency to it in the polypropylene/polyglecaprone mesh group.…”

“…Despite the 21 postoperative days, large fragments of the polyglecaprone barriers remained, surrounded by clusters of macrophages and giant foreign body cells. The use of synthetic meshes for the repair of defects in the abdominal wall, especially tissue separating meshes, implies a greater amount of degradable synthetic or biological polymers that determine an inflammatory response accompanied by a greater number of macrophages M1 and M2 and giant cells capable of leading to the biodegradation of this absorbable material and the involvement of the nonabsorbable filaments of the mesh, during the process of fibroplasia, incorporating the mesh to the tissue 24 .…”