Background
Polypropylene (PP) mesh is widely used to reinforce tissues. The foreign body reaction (FBR) to the implant is dominated by innate immune cells, especially macrophages. However, ...considerable numbers of adaptive immune cells, namely T cells, have also been regularly observed, which appear to play a crucial role in the long-term host response.
Methods
This study investigated the FBR to seven human PP meshes, which were removed from the abdomen for recurrence after a median of one year. Using immunofluorescence microscopy, the FBR was examined for various innate (CD11b
+
myeloid, CD68
+
macrophages, CD56
+
NK) and adaptive immune cells (CD3
+
T, CD4
+
T-helper, CD8
+
cytotoxic, FoxP3
+
T-regulatory, CD20
+
B) as well as “conventional” immune cells (defined as cells expressing their specific immune cell marker without co-expressing CD68).
Results
T-helper cells (19%) and regulatory T-cells (25%) were present at comparable rates to macrophages, and clustered significantly toward the mesh fibers. For all cell types the lowest proportions of “conventional” cells (< 60%) were observed at the mesh–tissue interface, but increased considerably at about 50–100 µm, indicating reduced stimulation with rising distance to the mesh fibers.
Conclusion
Both innate and adaptive immune cells participate in the chronic FBR to PP meshes with T cells and macrophages being the predominant cell types, respectively. In concordance with the previous data, many cells presented a “hybrid” pattern near the mesh fibers. The complexity of the immune reaction seen within the foreign body granuloma may explain why approaches focusing on specific cell types have not been very successful in reducing the chronic FBR.
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.
Implants like meshes for the reinforcement of tissues implement the formation of a persistent inflammation with an ambient fibrotic reaction. In the inflammatory infiltrate several distinct cell ...types have been identified, but CD68+ macrophages are supposed to be most important. To investigate the collaboration among the various cell types within the infiltrate we performed at explanted meshes from humans double fluorescence staining with CD68 as a constant marker and a variety of other antibodies as the second marker. The list of second markers includes lymphocytes (CD3, CD4, CD8, CD16, CD56, FoxP3, and CD11b) stem cells (CD34), leucocytes (CD45, CD15), macrophages (CD86, CD105, CD163, and CD206); deposition of EC matrix (collagen‐I, collagen‐III, MMP2, and MMP8); Ki67 as a marker for proliferation; and the tyrosine‐protein kinase receptor AXL. The present study demonstrates within the inflammatory infiltrate the abundant capability of CD68+ cells to co‐express a huge variety of other markers, including those of lymphocytes, varying between 5 and 83% of investigated cells. The observation of co‐staining was not restricted to a specific polymer but was seen with polypropylene fibers as well as with fibers made of polyvinylidene fluoride, although with differences in co‐expression rates. The persisting variability of these cells without the functional reduction toward differentiated mature cell types may favor the lack of healing at the interface of meshes.
Foreign bodies such as fibers of a surgical mesh induce a typical reaction with an inflammatory infiltrate that forms a surrounding granuloma. This infiltrate is dominated by macrophages, ...lymphocytes, and neutrophils, whereas its extent of collaboration is widely unknown. In this study, we analyzed 12 samples of surgical meshes explanted from humans by multiplex analyses with three different 5-marker panels - 1. macrophage panel: CD68, CD86, CD105, CD163, and CD206; 2. lymphocyte panel: CD3, CD4, CD8, CD20, and CD68; and 3. neutrophil panel: CD15, histone, MPO, NE, and CD68. Measurement of fluorescence intensity within nuclear masks resulting from DAPI nuclear staining allows exact quantification of cells considered "positive" at a user-defined mean intensity threshold of > 100. Obviously, however, there is no natural threshold as a biological criterion for an intensity that separates "positive" stained cells from unstained cells ("negative"). Multiplex staining of 5 markers always reveals a high rate of coexpression for almost all of the 2
possible marker combinations (= 32 combinations, when using 5 markers simultaneously). The present staining results demonstrate that various morphological and functional subtypes of macrophages, lymphocytes, and neutrophils are abundant in the foreign body granuloma (FBG), which were investigated by regions of interest (ROI) with an area of 1 mm
. The widespread coexpression of two or more markers underscores the complex collaboration network of the inflammatory infiltrate. The ability to combine spatial distribution with exact numerical analysis may offer new perspectives for our understanding of the complex interactions in this multidimensional process.
Mesh implant has been applied in hernia repair and urogynecological reconstruction. Polypropylene (PP) is now the most widely used material for non-resorbable mesh implants. A degradation phenomenon ...of PP mesh, which is apparent on the mesh surface as cracking, flaking and peeling, was discovered in the 1990's. This phenomenon of mesh implant has drawn attention because of mesh-related litigations. Polyvinylidene fluoride (PVDF), due to its high biocompatible performance, has been used since 2003 as an alternative material for non-resorbable mesh implants. Till now, no such degradation phenomenon of PVDF mesh has been reported, although limited study on PVDF mesh is available.
In this paper, we researched the degradation of PVDF meshes taking the degradation of PP mesh as a reference. The meshes analysed in this study were received from a previous animal experiment. To expose the surface of explanted meshes, a tissue removing method with protease was used and the result of this cleaning process was tested by X-ray Photoelectron Spectroscopy (XPS). The morphological condition of the mesh surface was compared using Scanning Electron Microscopy (SEM) and the chemical condition concerning degradation was analysed through Fourier Transform Infrared Spectroscopy (FTIR). The surface condition of PVDF mesh after 3-, 6-, 12- and 24-month implantation was illustrated and compared with two types of PP meshes.
XPS revealed an absence of nitrogen, confirming the successful removal of tissue residues using protease. SEM results presented no notable morphological surface change of the PVDF mesh and progressive surface cracking processes over time of both types of PP meshes. FTIR spectra of the implanted PVDF meshes had no considerable difference from the spectrum of the pristine mesh, while FTIR spectra of both types of PP meshes had extra chemical functional groups (carbonyl (CO) and hydroxyl (-OH) groups) increasing with implantation time, indicating progressive degradation. This study highlights the morphological and chemical stability of the PVDF mesh and demonstrates that the PVDF mesh is more resistant to degradation in comparison to the other two types of PP meshes.
•PVDF mesh is more resistant to degradation in vivo in comparison to PP mesh.•PVDF mesh undergoes no considerable morphological or chemical change up to 24 months after implantation.•A time-dependent progressive degradation behavior of PP mesh is shown.•Mesh preparation with protease is sufficient for removing biological tissue.
Liver cancer is one of the most frequently diagnosed and fatal cancers worldwide, with hepatocellular carcinoma (HCC) being the most common primary liver cancer. Hundreds of studies involving ...thousands of patients have now been analysed across different cancer types, including HCC, regarding the effects of immune infiltrates on the prognosis of cancer patients. However, for these analyses, an unambiguous delineation of the cancer area is paramount, which is difficult due to the strong heterogeneity and considerable inter-operator variability induced by qualitative visual assessment and manual assignment. Nowadays, however, multiplex analyses allow the simultaneous evaluation of multiple protein markers, which, in conjunction with recent machine learning approaches, may offer great potential for the objective, enhanced identification of cancer areas with further in situ analysis of prognostic immune parameters. In this study, we, therefore, used an exemplary five-marker multiplex immunofluorescence panel of commonly studied markers for prognosis (CD3 T, CD4 T helper, CD8 cytotoxic T, FoxP3 regulatory T, and PD-L1) and DAPI to assess which analytical approach is best suited to combine morphological and immunohistochemical data into a cancer score to identify the cancer area that best matches an independent pathologist's assignment. For each cell, a total of 68 individual cell features were determined, which were used as input for 4 different approaches for computing a cancer score: a correlation-based selection of individual cell features, a MANOVA-based selection of features, a multilayer perceptron, and a convolutional neural network (a U-net). Accuracy was used to evaluate performance. With a mean accuracy of 75%, the U-net was best capable of identifying the cancer area. Although individual cell features showed a strong heterogeneity between patients, the spatial representations obtained with the computed cancer scores delineate HCC well from non-cancer liver tissues. Future analyses with larger sample sizes will help to improve the model and enable direct, in-depth investigations of prognostic parameters, ultimately enabling precision medicine.
Schwann cell (SC) transplantation represents a promising therapeutic approach for traumatic spinal cord injury but is frustrated by barrier formation, preventing cell migration, and axonal ...regeneration at the interface between grafted SCs and reactive resident astrocytes (ACs). Although regenerating axons successfully extend into SC grafts, only a few cross the SC–AC interface to re-enter lesioned neuropil. To date, research has focused on identifying and modifying the molecular mechanisms underlying such scarring cell–cell interactions, while the influence of substrate topography remains largely unexplored. Using a recently modified cell confrontation assay to model SC–AC barrier formation in vitro, highly oriented poly(ε-caprolactone) nanofibers were observed to reduce AC reactivity, induce extensive oriented intermingling between SCs and ACs, and ultimately enable substantial neurite outgrowth from the SC compartment into the AC territory. It is anticipated that these findings will have important implications for the future design of biomaterial-based scaffolds for nervous tissue repair.
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