Complications of synthetic mesh inserted for stress urinary incontinence.

OBJECTIVE: To provide an update on the literature regarding the management of complications secondary to synthetic mesh placed to treat stress urinary incontinence (SUI). METHODS: We performed a systematic review of the literature using a multi-database structured search within OVID, the Medical Literature Analysis and Retrieval System Online (MEDLINE), the Excerpta Medica dataBASE (EMBASE) and Cochrane library databases; using the keywords: urology, incontinence, mesh and surgery. RESULTS: Several million synthetic polypropylene meshes have been inserted into women worldwide to manage SUI. Unfortunately, a significant number of women have now reported life-changing complications. We found a paucity of studies, heterogeneity of cohorts, poor long-term follow-up, and lack of evidence on the effective management of mesh-related complications. CONCLUSIONS: The contemporary evidence is low-level and often contradictory, which prevents robust recommendations regarding treatment. A prospective registry will be required to generate meaningful outcome data and help in the complex management of patients who have mesh-related complications.

A rare reaction to synthetic mono-filament sutures: a report of two cases.

Due to their clinical advantages, synthetic mono-filament sutures are dominantly used for postoperative wound closures. We present two patients who suffered rare skin reactions to either poliglecaprone 25 or glyconate sutures, following breast cancer lumpectomy. This report aims to make perioperative practitioners and clinicians aware of reactions to sutures and possible management options.

Hernia repair with polypropylene mesh is not associated with an increased risk of autoimmune disease in adult men.

PURPOSE: Synthetic mesh for herniorrhaphy has been placed under critical observation regarding the potential association of mesh placement and the subsequent development of autoimmune diseases. We sought to evaluate whether there is a link between synthetic polypropylene mesh repairs and the subsequent development of systemic/autoimmune disorders (SAID). STUDY DESIGN: Adult men undergoing hernia repair with mesh between January 2008 and December 2009 in New York State were identified using International Classification of Diseases, Ninth Revision, Modification procedure codes and Current Procedural Terminology Coding System, Fourth Edition codes. A control cohort of men undergoing colonoscopy was created with whom to compare outcomes. RESULTS: A total of 29,712 patients underwent hernia repair between January 2008 and December 2009. In the control cohort, 79,265 patients underwent colonoscopy. During the entire follow-up, 475 patients undergoing hernia repair and 1305 patients in the control cohort were diagnosed with autoimmune disease. When patients were matched based on demographics, comorbidities and procedure date, hernia repair was not associated with an increased risk of developing autoimmune disease over the entire follow-up time period. 1.6% of those in the hernia group vs. 1.7% of those in the colonoscopy group developed SAID [risk ratio (95% CI): hernia vs. colonoscopy 0.93(0.79-1.09)]. No association between mesh surgery and increased risks of SAID was found at any of the specified time points (6 months, 1 year, and 2-year follow-up). CONCLUSIONS: Mesh-based hernia repair was not associated with the development of autoimmune diseases compared to those undergoing routine screening colonoscopy.

Sugar-Modified Poly(propylene imine) Dendrimers Stimulate the NF-κB Pathway in a Myeloid Cell Line.

PURPOSE: Fourth-generation poly(propylene imine) dendrimers fully surface-modified by maltose (dense shell, PPI-m DS) were shown to be biocompatible in cellular models, which is important for their application in drug delivery. We decided to verify also their inherent bioactivity, including immunomodulatory activity, for potential clinical applications. We tested their effects on the THP-1 monocytic cell line model of innate immunity effectors. METHODS: To estimate the cytotoxicity of dendrimers the reasazurin assay was performed. The expression level of NF-κB targets: IGFBP3, TNFAIP3 and TNF was determined by quantitative real-time RT-PCR. Measurement of NF-κB p65 translocation from cytoplasm to nucleus was conducted with a high-content screening platform and binding of NF-κB to a consensus DNA probe was determined by electrophoretic mobility shift assay. The cytokine assay was performed to measure protein concentration of TNFalpha and IL-4. RESULTS: We found that PPI-m DS did not impact THP-1 viability and growth even at high concentrations (up to 100 µM). They also did not induce expression of genes for important signaling pathways: Jak/STAT, Keap1/Nrf2 and ER stress. However, high concentrations of 4th generation PPI-m DS (25-100 µM), but not their 3rd generation counterparts, induced nuclear translocation of p65 NF-κB protein and its DNA-binding activity, leading to NF-κB-dependent increased expression of mRNA for NF-κB targets: IGFBP3, TNFAIP3 and TNF. However, no increase in pro-inflammatory cytokine secretion was detected. CONCLUSION: We conclude that maltose-modified PPI dendrimers of specific size could exert a modest immunomodulatory effect, which may be advantageous in clinical applications (e.g. adjuvant effect in anti-cancer vaccines).

Effect of Hyperlipidemia and Plasma Cytokine Levels in Rats after Anterior Abdominal Wall Reconstruction with the Use of Synthetic Endoprostheses.

The effect of hyperlipidemia on the systemic production of cytokines was evaluated in the plasma of rats after anterior abdominal wall reconstruction with polypropylene (Esfil) and polytetrafluorethylene (Ecoflon) endoprostheses. The reference group was formed from animals without hyperlipidemia, in which anterior abdominal wall plasty was carried out with the use of the same endoprostheses. Intact rats without hyperlipidemia and intervention served as the control. Hypercytokinemia was detected on days 1-10 after reconstructive surgery on the anterior abdominal wall. Polytetrafluoroethylene alloplasty was associated with higher plasma production of pro- and anti-inflammatory cytokines, which characterized mainly the implant reactogenicity. Hyperlipidemia modified the reactivity of immunocompetent cells to the endoprosthesis. A progressive decrease in the content of proinflammatory cytokines (IL-1ß and TNF-α) was observed by day 10 after endoprosthesis implantation, this decrease being more manifest in response to polytetrafluoroethylene. High plasma levels of pro- and antiinflammatory cytokines (IL-1ß, INF-α, IFN-γ, and IL-10) were detected in hyperlipidemic rats on day 1 after polypropylene plasty; by day 10, the plasma level of IFN-γ increased, which reflected positive activation of Th1 lymphocytes.

Sources of Reactive Oxygen and Nitrogen Species in Tissue Microenvironment of Hernioplasty Materials.

Titanium and polypropylene mesh endoprostheses were implanted into the rat abdominal cavity and the populations of cells migrating to their surface were analyzed. On both materials, the cells were presented mainly by macrophages that proliferated, activated, and fused to form multinuclear cells. Contact with the foreign surface triggered superoxide anion generation and myeloperoxidase synthesis by macrophages (these processes were more intense on polypropylene implants than on titanium ones) and stimulated production of nitric oxide by macrophage. It was hypothesized that the effects of free nitrogen and oxygen radicals lead to oxidation and destruction of the polypropylene endoprosthesis surface.

Preparation of a small intestinal submucosa modified polypropylene hybrid mesh via a mussel-inspired polydopamine coating for pelvic reconstruction.

Pelvic organ prolapse (POP) is a serious health issue that affects many adult women. Surgical treatments for POP patients comprise a common strategy in which scaffold materials are used to reconstruct the prolapsed pelvic. However, the existing materials for pelvic reconstruction cannot meet clinical requirements in terms of biocompatibility, mechanics and immunological rejection. To address these concerns, polypropylene (PP) mesh was selected because of its strong mechanical properties. Small intestinal submucosa (SIS) was used to modify the PP mesh via a mussel-inspired polydopamine coating to enhance its biocompatibility. The scanning electron microscopy (SEM) and atomic force microscopy (AFM) results demonstrated that SIS was successfully conjugated on the surface of the PP mesh. Moreover, the cytotoxicity results indicated that the PP mesh and SIS-modified PP mesh were safe to use. Furthermore, in vivo tests demonstrated that the fibroplasia around the implanted site in the SIS-modified PP mesh group was significantly less than the fibroplasia around the PP mesh group. In addition, the immunohistochemistry staining results indicated that the expression of pro-inflammatory macrophages (M1) was substantially lower and that the expression of pro-healing macrophages (M2) was higher in the SIS-modified PP mesh group. Furthermore, ELISA detection indicated that the expression of IL-1ß and IL-6 in the SIS-modified PP mesh group was reduced compared with the PP mesh group. These findings suggest that a SIS-modified polypropylene hybrid mesh via a mussel-inspired polydopamine coating is a promising approach in pelvic reconstruction.

Effects of polypropylene and polytetrafluoroethylene prostheses for abdominal plasty on local and systemic cytokine production.

We studied the effects of Esphyl polypropylene mesh and Ecoflon polytetrafluoroethylene endoprostheses on local and systemic production of cytokines. Polytetrafluoroethylene is a more reactogenic material than polypropylene; it stimulates mainly the local production of pro-inflammatory cytokines. The local anti-inflammatory effect of polypropylene was less pronounced, but persisted for longer time.

Inducible nitric oxide synthase inhibition increases MMP-2 activity leading to imbalance between extracellular matrix deposition and degradation after polypropylene mesh implant.

Prosthetic mesh implants are commonly used to correct abdominal wall defects. However, success of the procedure is conditioned by an adequate inflammatory response to the device. We hypothesized that nitric oxide produced by nitric oxide synthase 2 (NOS2) and MMP-2 and -9 participate in response induced by mesh implants in the abdominal wall and, consequently, affect the outcome of the surgical procedure. In the first step, temporal inflammatory markers profile was evaluated. Polypropylene meshes were implanted in the peritoneal side of the abdominal wall of C57Black mice. After 2, 4, 7, 15, and 30 days, tissues around the mesh implant were collected and inflammatory markers were analyzed. In the second step, NOS2 activity was inhibited with nitro-L-arginine methyl ester (L-NAME). Samples were collected after 15 days (when inflammation was reduced), and the inflammatory and tissue remodeling markers were investigated. Polypropylene mesh implant induced a pro-inflammatory environment mediated by intense MMP-2 and -9 activities, NO release, and interleukin-1ß production peaking in 7 days and gradually decreasing after 15 days. NOS2 inhibition increased MMP-2 activity and resulted in a higher visceral adhesion incidence at the mesh implantation site when compared with non-treated animals that underwent the same procedure. We conclude that NOS2-derived NO is crucial for adequate response to polypropylene mesh implant integration in the peritoneum. NO deficiency results in an imbalance between extracellular matrix deposition/degradation contributing to visceral adhesions incidence.

Porcine urinary bladder matrix-polypropylene mesh: a novel scaffold material reduces immunorejection in rat pelvic surgery.

INTRODUCTION AND HYPOTHESIS: The present study set out to modify polypropylene vaginal surgical material using porcine urinary bladder matrix (UBM) in order to improve biocompatibility. The aim was to develop a compound scaffold that induced less vaginal erosion and to evaluate host immunoreactivity to this material in vivo. METHODS: Forty-eight Sprague-Dawley rats were randomly divided into four equal groups. One group underwent a sham operation, and the other groups underwent vaginal implantation with different materials: UBM (U); UBM + polypropylene (UP); or polypropylene (P). The host tissue response was determined by macro-observation, and by histological and immunohistochemical methods at 7, 14, 21, or 28 days after surgery. RESULTS: The inflammation reaction was strongest throughout the entire observation time in Group P, but was weaker and had a tendency to decrease with time in Groups U and UP. The presence of the UBM material in the compound scaffold allowed the polypropylene to fuse with newly proliferating surrounding tissue and resulted in less rejection of the material by the host, as indicated by the reduced appearance of CD4-, and CD8-positive cells. CONCLUSIONS: Porcine UBM allowed mechanical isolation of polypropylene, and also reduced the immune reaction to polypropylene. This study suggests that the UBM + polypropylene compound scaffold may be a promising material for clinical use in pelvic reconstruction surgery.

Engineering complement activation on polypropylene sulfide vaccine nanoparticles.

The complement system is an important regulator of both adaptive and innate immunity, implicating complement as a potential target for immunotherapeutics. We have recently presented lymph node-targeting, complement-activating nanoparticles (NPs) as a vaccine platform. Here we explore modulation of surface chemistry as a means to control complement deposition, in active or inactive forms, on polypropylene sulfide core, block copolymer Pluronic corona NPs. We found that nucleophile-containing NP surfaces activated complement and became functionalized in situ with C3 upon serum exposure via the alternative pathway. Carboxylated NPs displayed a higher degree of C3b deposition and retention relative to hydroxylated NPs, upon which deposited C3b was more substantially inactivated to iC3b. This in situ functionalization correlated with in vivo antigen-specific immune responses, including antibody production as well as T cell proliferation and IFN-γ cytokine production upon antigen restimulation. Interestingly, inactivation of C3b to iC3b on the NP surface did not correlate with NP affinity to factor H, a cofactor for protease factor I that degrades C3b into iC3b, indicating that control of complement protein C3 stability depends on architectural details in addition to factor H affinity. These data show that design of NP surface chemistry can be used to control biomaterials-associated complement activation for immunotherapeutic materials.

Surface chemistry influences implant-mediated host tissue responses.

Implant-mediated fibrotic reactions are detrimental to the performance of encapsulated cells, implanted drug release devices, and sensors. To improve the implant function and longevity, recent research has emphasized the need for inducing alterations in cellular responses. Although material surface functional groups have been shown to be potent in affecting cellular activity in vitro and short-term in vivo responses, these groups appear to have little influence on long-term in vivo fibrotic reactions, possibly as a result of insufficient interactions between recruited host cells and functional groups on the implants. To maximize the influence of functionality on cells, and to mimic drug release microspheres, functionalized micron-sized particles were created and tested for their ability in modulating tissue responses to biomaterial implants. In this work, the surfaces of polypropylene particles were controllably coated with four different functional groups, specifically -OH, -NH(2), -CF(x), and -COOH, using a radio frequency glow discharge plasma polymerization technique. The effect of these surface functionalities on host tissue responses were then evaluated using a mice subcutaneous implantation model. Major differences were observed in contrasting tissue response to the different chemistries. Surfaces with -OH and -NH(2) surface groups induced the thickest fibrous capsule accompanied with the greatest cellular infiltration into the implants. In contrast, surfaces with -CF(x) and -COOH exhibited the least inflammatory/fibrotic responses and cellular infiltrations. The present results clearly demonstrate that, by increasing the available functionalized surface area and spatial distribution, the effect of surface chemistry on tissue reactivity can be substantially enhanced.

Tensile strength and host response towards different polypropylene implant materials used for augmentation of fascial repair in a rat model.

We compared inflammatory response, fibrosis and biomechanical properties of different polypropylene materials from one manufacturer (Tyco Healthcare) in a rat model for primary fascial repair. Full-thickness abdominal wall defects were primarily repaired using 'overlay' technique. Multifilament implants were Surgipro SPM and SPMW, the latter a wider-weave type of the former. Monofilament SPMM implants and polypropylene suture repair (Surgipro II) served as controls. Explants were evaluated macroscopically and changes in thickness, shrinkage and tensile strength were measured. Inflammatory and connective tissue response was assessed on haematoxylin-eosin and Movat stains. Immunohistochemistry was done to localise rat macrophages/monocytes. Multifilament materials induced a shorter acute inflammatory response and more pronounced chronic inflammatory reaction compared to monofilament implants. Macrophages could be found deep in interstices 7.5 by 12.5 microm. No difference in collagen deposition and neovascularisation was observed. At 90 days time point, explants reconstructed with tighter woven multifilament SPM were weaker than sutured or SPMM controls. Overall shrinkage of 10% was comparable for all groups.

Tensile strength and host response towards silk and type i polypropylene implants used for augmentation of fascial repair in a rat model.

OBJECTIVE: We compared host response, architectural integration and tensile strength of two different macroporous silk constructs to a polypropylene type I implant in a rat model for augmentation of primary fascial defect repair. MATERIALS AND METHODS: Animals were sacrificed on days 7, 14, 30 and 90 after implantation. The explants were evaluated macroscopically for infections, herniations and adhesions, mechanically for tensile strength, and histopathologically, to evaluate collagen deposition and inflammatory response. RESULTS: The tensile strength of the explants showed a gradual increase for all materials. All implants uniformly shrank around one fifth by 90 days. In the silk implants, the inflammatory reaction showed a remarkable higher number of foreign body giant cells that characteristically spread from the periphery into implants. Collagen deposition was comparable for all the materials. In Silk a higher grade of neovascularisation was observed. CONCLUSION: Silk explants expressed high tensiometric strength, which was associated with a marked fibrotic process. The silk implants induced a strong foreign body reaction accompanied by microscopic signs of architectural degradation at 90 days. Polypropylene explants showed a more moderate foreign body reaction without architectural disturbance.

Comparison of host response to polypropylene and non-cross-linked porcine small intestine serosal-derived collagen implants in a rat model.

OBJECTIVE: To compare the host response, architectural integration and tensile strength of polypropylene and porcine small intestine submucosa-derived implants in a rat model. DESIGN: Experimental study. SETTING: Center for Surgical Technologies, Faculty of Medicine, Katholieke Universiteit Leuven, Belgium. SAMPLE: Forty-eight adult male Wistar rats weighing 220-250 g randomised to receive either implant. METHODS: Full thickness abdominal wall defects were primarily repaired with polypropylene mesh (Marlex) (MX group) or porcine small intestine submucosa (Surgisis) (SIS group). Animals were sacrificed at 7, 14, 30 and 90 days after implantation. MAIN OUTCOME MEASURES: The presence of herniation, infection and intra-peritoneal adhesions. Change in thickness and tensile strength of implant. Histopathological and immunohistochemical appearances of inflammatory response and collagen deposition. RESULTS: Implants from the SIS group showed a short term increase in thickness in the first 14 days. Formation of adhesions was significantly more intense in the MX group at 30 days, and more extensive in the SIS group at 90 days. Tensile strength increased over time in both groups but was significantly lower in the SIS group than the MX group at 30 days. Implants in the MX group showed a more pronounced inflammatory response and more pronounced new vessel formation than the SIS group. Collagen formation was initially more fibrous and better organised in the MX group but became greater in the SIS group at 90 days. CONCLUSIONS: Biologically derived implant material induced a less pronounced inflammatory response and differences in collagen deposition. At 30 days tensile strength was weaker in the biological implant group but was equivalent by 90 days. These differences may have implications for the in vivo performance of the materials.

Acute inflammatory response after inguinal and incisional hernia repair with implantation of polypropylene mesh of different size.

BACKGROUND: The purpose of this study was to assess the modifications of interleukin (IL)-6, C-reactive protein (CRP), leukocytes and fibrinogen after implantation of polypropylene mesh. METHODS: Thirty-six patients were included in this study and divided into two groups. To the first group were allocated patients affected by inguinal hernia and undergoing conventional repair (subgroup Ia) or hernioplasty with 40-cm(2) polypropylene mesh (subgroup Ib). To the second group were allocated patients affected by incisional hernia and undergoing conventional repair (subgroup IIa) or incisional hernia repair with 400-cm(2) polypropylene mesh (subgroup IIb). Peripheral venous blood samples were collected 24 h before surgery and then 6, 24, 48 and 168 h postoperatively. RESULTS: We present evidence that serum levels of IL-6, CRP, leukocytes and fibrinogen were significantly increased postoperatively in all subgroups compared with their baseline values. In particular, the production of inflammatory mediators was higher in subgroups Ib vs Ia and IIb vs IIa. Comparing the entities of the inflammatory responses among various groups we found that it was clear that they were similar in subgroups Ib and IIa, and that the highest were in subgroup IIb and the lowest in subgroup Ia. CONCLUSION: The data show that conventional inguinal and incisional hernia repair induces an inflammatory response, which is smaller than that observed if both operations are carried out with polypropylene meshes. Furthermore, the results suggest that a larger mesh is associated with a higher production of inflammation mediators.

A histologic and immunohistochemical analysis of defective vaginal healing after continence taping procedures: a prospective case-controlled pilot study.

OBJECTIVE: The purpose of this study was to investigate vaginal rejection of polypropylene mesh after continence taping procedures. STUDY DESIGN: Of 700 women who had undergone the procedures, 17 women with sling erosion and 7 women with voiding difficulty or symptomatic vagina prolapse (control subjects) underwent histopathologic evaluation and immunohistochemistry. RESULTS: Seven women whose condition was not responding to conservative treatment and debridements had the exposed suburethral tape excised, which revealed predominant foreign body reaction and fragmented mesh that was surrounded by histiocytes and dense fibrosis. Immunohistochemical analysis revealed that the cell density percentage of CD 20+ cells was statistically significantly greater in the persistent defective healing group than in either the single-debridement or control group ( P = .014 and P = .014, respectively). We found statistically significant differences between the persistent defective healing and single-debridement groups and between the former and control groups in the ratios of T and B cells ( P = .035 and P = .022, respectively). CONCLUSION: The rate of defective vaginal healing after the procedures was 2.4%. Removal of the prosthesis and surrounding tissue at various times for the 7 women resulted in histopathologic findings that suggested a immunologic reaction. The rate of persistent defective healing of the vagina was 1%.

Influence of implantation interval on the long-term biocompatibility of surgical mesh.

BACKGROUND: The aim was to study the long-term tissue response to polypropylene mesh. METHODS: This was a retrieval study that investigated 76 polypropylene meshes with a median implantation interval of 18 (range 2-180) months. Mesh was explanted following hernia recurrence, infection or pain. The median implantation interval was 20 (range 4-180) months in the recurrence group, 30 (range 5-48) months in the pain group and 10 (range 2-56) months in the infection group (P < 0.05, infection versus pain or recurrence). The inflammatory response was determined by immunohistochemistry of macrophages (CD68), polymorphonuclear granulocytes (CD15) and T and B lymphocytes (CD3 and CD20). The cell turnover within the interface mesh fibre-recipient tissue was measured by TUNEL for apoptosis or DNA strand breaks, Ki67 for cell proliferation and heat-shock protein (HSP) 70 for cell stress. RESULTS: With the exception of HSP-70, levels of all variables decreased over time. Sex, age, type of previous operation or location of the mesh did not have a significant influence. CONCLUSION: Long-term incorporated polypropylene mesh in humans has a more favourable tissue response with increasing implantation interval.

Comparison of complement activation by silicone intraocular lenses and polymethylmethacrylate intraocular lenses with polypropylene loops.

Silicone intraocular lenses are undergoing clinical investigation for use in the United States. We compared the ability of silicone intraocular lenses to activate the complement system in human sera with that of polymethylmethacrylate intraocular lenses with polypropylene loops using a radioimmunoassay that measures levels of activated complement fragments. Sera incubated with polymethylmethacrylate lenses with polypropylene loops had higher levels of C3a and C5a, but not C4a, than control sera incubated without intraocular lenses. On the other hand, there were no differences in levels of C3a, C4a, and C5a between sera incubated with silicone lenses and control sera. These results suggest that polymethylmethacrylate lenses with polypropylene loops activate the alternative pathway of complement, while silicone lenses do not.