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

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.

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

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.

META Score: An International Consensus Scoring System on Mesh-Tissue Adhesions.

BACKGROUND: Currently, the lack of consensus on postoperative mesh-tissue adhesion scoring leads to incomparable scientific results. The aim of this study was to develop an adhesion score recognized by experts in the field of hernia surgery. METHODS: Authors of three or more previously published articles on both mesh-tissue adhesion scores and postoperative adhesions were marked as experts. They were queried on seven items using a modified Delphi method. The items concerned the utility of adhesion scoring models, the appropriateness of macroscopic and microscopic variables, the range and use of composite scores or subscores, adhesion-related complications and follow-up length. This study comprised two questionnaire-based rounds and one consensus meeting. RESULTS: The first round was completed by 23 experts (82%), the second round by 18 experts (64%). Of those 18 experts, ten were able to participate in the final consensus meeting and all approved the final proposal. From a total of 158 items, consensus was reached on 90 items. The amount of mesh surface covered with adhesions, tenacity and thickness of adhesions and organ involvement was concluded to be a minimal set of variables to be communicated separately in each future study on mesh adhesions. CONCLUSION: The MEsh Tissue Adhesion scoring system is the first consensus-based scoring system with a wide backing of renowned experts and can be used to assess mesh-related adhesions. By including this minimal set of variables in future research interstudy comparability and objectivity can be increased and eventually linked to clinically relevant outcomes.

Elastic TPU Mesh as Abdominal Wall Inlay Significantly Reduces Defect Size in a Minipig Model.

Background: The open abdomen with mesh implantation, followed by early reoperation with fascial closure, is a modern surgical approach in difficult clinical situations such as severe abdominal sepsis. As early fascial closure is not possible in many cases, mesh-mediated fascial traction is helpful for conditioning of a minimized ventral hernia after open abdomen. The aim of this study was to evaluate the clinical utilization of an innovative elastic thermoplastic polyurethane mesh (TPU) as an abdominal wall inlay in a minipig model. Methods: Ten minipigs were divided in two groups, either receiving an elastic TPU mesh or a nonelastic polyvinylidene fluoride (PVDF) mesh in inlay position of the abdominal wall. After 8 weeks, mesh expansion and abdominal wall defect size were measured. Finally, pigs were euthanized and abdominal walls were explanted for histological and immunohistochemical assessment. Results: Eight weeks after abdominal wall replacement, transversal diameter of the fascial defect in the TPU group was significantly smaller than in the PVDF group (4.5 cm vs. 7.4 cm; p = 0.047). Immunhistochemical analysis showed increased Ki67 positive cells (p = 0.003) and a higher number of apoptotic cells (p = 0.047) after abdominal wall replacement with a TPU mesh. Collagen type I/III ratio was increased in the PVDF group (p = 0.011). Conclusion: Implantation of an elastic TPU mesh as abdominal wall inlay is a promising approach to reduce the size of the ventral hernia after open abdomen by mesh-mediated traction. However, this effect was associated with a slightly increased foreign body reaction in comparison to the nonelastic PVDF.

MRI Evaluation of an Elastic TPU Mesh under Pneumoperitoneum in IPOM Position in a Porcine Model.

BACKGROUND: The frequency of laparoscopic approaches increased in hernia surgery over the past years. After mesh placement in IPOM position, the real extent of the meshes configurational changes after termination of pneumoperitoneum is still largely unknown. To prevent a later mesh folding it might be useful to place the mesh while it is kept under tension. Conventionally used meshes may lose their Effective Porosity under these conditions due to poor elastic properties. The aim of this study was to evaluate a newly developed elastic thermoplastic polyurethane (TPU) containing mesh that retains its Effective Porosity under mechanical strain in IPOM position in a porcine model. It was visualized under pneumoperitoneum using MRI in comparison to polyvinylidenefluoride (PVDF) meshes with similar structure. METHODS: In each of ten minipigs, a mesh (TPU containing or native PVDF, 10 × 20 cm) was randomly placed in IPOM position at the center of the abdominal wall. After 8 weeks, six pigs underwent MRI evaluation with and without pneumoperitoneum to assess the visibility and elasticity of the mesh. Finally, pigs were euthanized and abdominal walls were explanted for histological and immunohistochemical assessment. The degree of adhesion formation was documented. RESULTS: Laparoscopic implantation of elastic TPU meshes in IPOM position was feasible and safe in a minipig model. Mesh position could be precisely visualized and assessed with and without pneumoperitoneum using MRI after 8 weeks. Elastic TPU meshes showed a significantly higher surface increase under pneumoperitoneum in comparison to PVDF. Immunohistochemically, the amount of CD45-positive cells was significantly lower and the Collagen I/III ratio was significantly higher in TPU meshes after 8 weeks. There were no differences regarding adhesion formation between study groups. CONCLUSIONS: The TPU mesh preserves its elastic properties in IPOM position in a porcine model after 8 weeks. Immunohistochemistry indicates superior biocompatibility regarding CD45-positive cells and Collagen I/III ratio in comparison to PVDF meshes with a similar structure.

Risk-adjusted procedure tailoring leads to uniformly low complication rates in ventral and incisional hernia repair: a propensity score analysis and internal validation of classification criteria.

BACKGROUND: The usual approach in hernia surgery is to select the ideal repair method independent of the patient's characteristics. In the present study, we change the approach to ask which technique is best for the individual patient`s risk profile. For this, two criteria are important: does the patient need reconstruction of the abdominal wall? or does he or she need treatment of symptoms without being exposed to unnecessarily high perioperative risks? METHODS: In a heuristic selection procedure, 486 consecutive patients were classified according to their characteristics as low-risk or high-risk for postoperative complications. Low-risk patients preferentially underwent open abdominal wall reconstruction with mesh (MFR + mesh), high-risk patients mainly a bridging-mesh procedure, either by laparoscopic (Lap.-IPOM) or open approach (Open-IPOM). Primary outcome was the incidence of postoperative complications. Secondary outcome was the recurrence-free interval. The propensity score was used for covariate adjustment analyzing recurrence rate as well as postoperative complications using Cox regression and logistic regression, respectively. RESULTS: Comparison of all surgical procedures showed risk factors had no independent influence on occurrence of complications (p = 0.110). Hernial gap width was an independent factor for occurrence of complications (p = 0.002). Propensity score adjustment revealed Lap.-IPOM to have a significantly higher recurrence rate than MFR + mesh (HR 2.367, 95% CI 1.123-4.957, p = 0.024). Three or more risk factors were protective against recurrence (HR 0.454, 95% CI 0.221-0.924, p = 0.030). In the univariate Cox regression analysis for recurrence, age >50 years was a protective prognostic factor (HR 0.412, 95% CI 0.245-0.702, p = 0.002). CONCLUSIONS: The classification criteria applied were internally validated. The heuristic algorithm ensured that patients at high-risk of complications did not have a higher perioperative complication rate than patients at low-risk.

Analysis of adhesion formation of a new elastic thermoplastic polyurethane (TPU) mesh in comparison to polypropylene (PP) meshes in IPOM position.

BACKGROUND: Postsurgical adhesions severely affect the patients' quality of life causing various complications like bowel obstruction or chronic pain. Especially the implantation of alloplastic prostheses in IPOM position for hernia repair carries a high risk of adhesion formation due to the close contact between mesh and viscera. The extent of adhesions mainly depends on the type and textile characteristics of the implanted mesh. The aim of this study was to examine the degree of adhesion formation of a newly developed, elastic thermoplastic polyurethane (TPU) mesh in comparison to polypropylene (PP) meshes in IPOM position in a rabbit model. METHODS: Sixteen female chinchilla rabbits were laparoscopically operated. Two different meshes were placed to the left and the right lower abdominal wall in IPOM position in each rabbit. After 7 or 21 days, midline laparotomy was performed, the degree of adhesion formation was examined by the Diamond score and mesh elongation was measured under a force of 3N. Finally, the abdominal walls were explanted for immunohistochemical and histopathological investigations. RESULTS: TPU meshes showed significantly lower Diamond scores than PP meshes. After explantation, mesh elongation of the TPU mesh was significantly larger than expansion of PP under a force of 3N. Thus, the TPU mesh preserved its elastic properties after 7 and 21 days. The amount of CD68 positive, Ki67 positive and apoptotic cells within the granuloma around the fibers did not show significant differences between the study groups. CONCLUSIONS: The newly developed TPU mesh seems to reduce peritoneal adhesion formation in IPOM position in a rabbit model compared to PP meshes after 7 and 21 days. Immunohistochemistry did not reveal differences in biocompatibility of the two meshes used.