Characterization of the T-cell response to polypropylene mesh in women with complications.

BACKGROUND: Polypropylene mesh is used widely for surgical treatment of pelvic organ prolapse and stress urinary incontinence. Although these surgeries demonstrate favorable functional and anatomic outcomes, their use has been limited by complications, the 2 most common being exposure and pain. Growing evidence suggests that T lymphocytes play a critical role in the regulation of the host response to biomaterials. OBJECTIVE: The purpose of this study was to define and characterize the T-cell response and to correlate the response to collagen deposition in fibrotic capsules in mesh tissue complexes that are removed for the complications of pain vs exposure. STUDY DESIGN: Patients who were scheduled to undergo a surgical excision of mesh for pain or exposure at Magee-Women's Hospital were offered enrollment. Forty-two mesh-vagina tissue complexes were removed for the primary complaint of exposure (n=24) vs pain (n=18). Twenty-one patients agreed to have an additional vaginal biopsy away from the site of mesh that served as control tissue. T cells were examined via immunofluorescent labeling for cell surface markers CD4+ (Th), CD8+ (cytotoxic) and foxp3 (T-regulatory cell). Frozen sections were stained with hematoxylin-eosin for gross morphologic condition and picrosirius red for collagen fiber analysis. Interrupted sodium-dodecyl sulfate gel electrophoresis was used to quantify the content of collagens type I and III, and the collagen III/I ratio. Transforming growth factor-ß and connective tissue growth factor, which are implicated in the development of fibrosis, were measured via enzyme-linked immunosorbent assays. Data were analyzed with the Student's t tests, mixed effects linear regression, and Spearman's correlation coefficients. RESULTS: Demographic data were not different between groups, except for body mass index, which was 31.7 kg/m2 for the exposure group and 28.2 kg/m2 for pain (P=.04). Tissue complexes demonstrated a marked, but highly localized, foreign body response. We consistently observed a teardrop-shaped fibroma that encapsulated mesh fibers in both pain and exposure groups, with the T cells localized within the tip of this configuration away from the mesh-tissue interface. All 3 T-cell populations were significantly increased relative to control: CD4+ T helper (P<.001), foxp3+ T regulatory (P<.001), and CD8+ cytotoxic T cell (P=.034) in the exposure group. In the pain group, only T-helper (P<.001) and T-regulatory cells (P<.001) were increased, with cytotoxic T cells (P=.520) not different from control. Picrosirius red staining showed a greater area of green (thin) fibers in the exposure group (P=.025) and red (thick) fibers in the pain group (P<.001). The ratio of area green/(yellow + orange + red) that represented thin vs thick fibers was significantly greater in the exposure group (P=.005). Analysis of collagen showed that collagen type I was increased by 35% in samples with mesh complications (exposure and pain) when compared with control samples (P=.043). Strong correlations between the profibrosis cytokine transforming growth factor-ß and collagen type I and III were found in patients with pain (r≥0.833; P=.01) but not exposure (P>.7). CONCLUSION: T cells appear to play a critical role in the long-term host response to mesh and may be a central pathway that leads to complications. The complexity of this response warrants further investigation and has the potential to broaden our understanding of mesh biology and clinical outcomes.

How have new bearing surfaces altered the local biological reactions to byproducts of wear and modularity?

BACKGROUND: The biologic reactions to byproducts of wear or corrosion can involve innate and adaptive processes and are dependent on many factors, including the composition, size, surface properties, shape, and concentration of debris. QUESTIONS/PURPOSES: We used a systematic literature review to compare the reported patterns of inflammation in tissues around total hip implants with the goal of identifying whether there are unique or characteristic patterns associated with the newer bearing options or modular components. METHODS: A search of the Ovid Medline database between 1996 and early December 2013 identified articles that compared the histology around six implant groups: (1) metal-on-metal; (2) ceramic-on-ceramic; (3) metal-on-crosslinked polyethylene; (4) metal-on-conventional polyethylene with or (5) without modularity; and (6) tissue obtained at primary arthroplasty. Our initial search yielded 865 citations. After excluding articles that lacked a quantitative or semiquantitative description of histologic findings in periprosthetic tissue, we reviewed 34 articles. RESULTS: No pattern of inflammation is specific for any given bearing combination. Histologic features suggestive of an adaptive immune response appear to be more frequent and of greater magnitude in failed metal-on-metal implants, but tissues around many failed metal-on-metal implants show features of an "innate" foreign body reaction without lymphocytes. Occasional nonmetal-on-metal implants show features of an immune reaction, possibly associated with metal particles. Modular connections are one source of metal debris in nonmetal-on-metal implants. Features of an immune reaction appear rare in ceramic-on-ceramic implants that lack corrosion. Insufficient reports are available to characterize the biologic response to crosslinked polyethylene. CONCLUSIONS: All total hip bearing combinations will wear in vivo, and modular interfaces are a likely source of metal that may be associated with a biological response regardless of the composition of the bearing surfaces. Surgeons must weigh the potential advantages of each articular combination and modular connection with the potential adverse tissue reactions in any given patient. Additional work is needed to clarify the implant and host-related factors associated with adverse tissue reactions and that seem to induce an immune reaction in some patients.

Biological activity and migration of wear particles in the knee joint: an in vivo comparison of six different polyethylene materials.

Wear of polyethylene causes loosening of joint prostheses because of the particle mediated activity of the host tissue. It was hypothesized that conventional and crosslinked polyethylene particles lead to similar biological effects around the knee joint in vivo as well as to a similar particle distribution in the surrounding tissues. To verify these hypotheses, particle suspensions of six different polyethylene materials were injected into knee joints of Balb/C mice and intravital microscopic, histological and immunohistochemical evaluations were done after 1 week. Whereas the biological effects on the synovial layer and the subchondral bone of femur and tibia were similar for all the polyethylenes, two crosslinked materials showed an elevated cytokine expression in the articular cartilage. Furthermore, the distribution of particles around the joint was dependent on the injected polyethylene material. Those crosslinked particles, which remained mainly in the joint space, showed an increased expression of TNF-alpha in articular cartilage. The data of this study support the use of crosslinked polyethylene in total knee arthroplasty. In contrast, the presence of certain crosslinked wear particles in the joint space can lead to an elevated inflammatory reaction in the remaining cartilage, which challenges the potential use of those crosslinked polyethylenes for unicondylar knee prostheses.

[Efficacy study of immunomodulator Gepon in treatment of oral membrane diseases in patients with complications in the form of filling material extrusion into mandibular canal].

Experience in new domestic immunomodulator Gepon application in practice of treatment of virus diseases and their manifestations in oral cavity of patients with complications in the form of filling material extrusion into mandibular canal is submitted. In a combination to traditional techniques of the treatment the preparation has shown high efficacy.