Characterization of the T-Cell Response to Polypropylene Mesh in Women With Complications

Tennyson, Lauren; Rytel, Matthew; Palcsey, Stacy; Meyn, Leslie A.; Liang, Rui; Moalli, Pamela

doi:10.1097/01.ogx.0000557738.46753.6a

Cited by 4 publications

(10 citation statements)

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“…The abundant expression of CD68, CD45, as well as CD8 within the FBG, suggested the possibility that macrophages alone may not be playing the decisive part. Consistently, Tennyson et al (2018) analyzed tissue reactions to explanted pelvic floor meshes and confirmed the presence of abundant lymphocytes, for example, CD4+ helper T cells, CD8+ cytotoxic T cells, or FOXP3+ regulatory T cells. Furthermore, our observation of widespread positive staining of different markers suggested that cells may co‐express some of them.…”

Section: Introductionmentioning

confidence: 65%

CD68+ macrophages as crucial components of the foreign body reaction demonstrate an unconventional pattern of functional markers quantified by analysis with double fluorescence staining

et al. 2020

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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.

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Section: Introductionmentioning

confidence: 65%

CD68+ macrophages as crucial components of the foreign body reaction demonstrate an unconventional pattern of functional markers quantified by analysis with double fluorescence staining

et al. 2020

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“…Moreover, underlying pro-inflammatory conditions, such as obesity, diabetes, smoking, and ageing contribute to complications in other biomaterial applications, such as breast or orthopaedic implants 61,62 , but have not been investigated specifically in POP or SUI mesh complications. 59,63 [H1] Surgical risk factors Surgical risk factors, such as the experience of the surgeon and surgical technique, have been linked to rates of mesh complications following pelvic floor reconstructive surgery. 18,53 Some clinical studies demonstrate that avoiding a vaginal incision suture line being in direct contact with the mesh material could decrease mesh exposure.…”

Section: [H1] Patient-specific Risk Factorsmentioning

confidence: 99%

“…However, some studies have examined explanted PPL mesh and vaginal tissue from patients treated for POP or SUI who had mesh removal because of pain or exposure. 29,46,63,[81][82][83][84] These studies often combine patients with SUI and POP, so understanding how responses differ between biological niches is not always possible. Typical of the FBR, a fibrous capsule and a dense cellular infiltrate of predominantly macrophages has been observed around the excised tissues (Figure 1).…”

Section: [H1] Patient-specific Risk Factorsmentioning

confidence: 99%

“…86 Mesh-tissue complexes from patients in either pain or exposure groups have demonstrated similar histological properties (such as extent and location of fibrotic tissue), but studies examining immune cell populations suggest that these two symptoms could represent different pathophysiological responses to mesh. 46,63 In PPL mesh and tissue explanted from women with a primary report of pain following pelvic surgery, a progressive fibrotic response has been observed, characterised by a high proportion of collagen type I and III fibres and high levels of transforming growth factor β (TGFß). 29,46,63 The percentage of profibrotic and/or remodelling M2 macrophages was found to positively correlate with the amount of interleukin 4 (IL-4) and interleukin 10 (IL-10) in these patients, consistent with tissue deposition and encapsulation.…”

Section: [H1] Patient-specific Risk Factorsmentioning

confidence: 99%

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Host–biomaterial interactions in mesh complications after pelvic floor reconstructive surgery

et al. 2021

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Polypropylene (PPL) mesh is widely used in pelvic floor reconstructive surgery for prolapse and stress urinary incontinence. However, some women, particularly those women treated using transvaginal PPL mesh placement for prolapse, experience intractable pain and mesh exposure or extrusion. Explanted tissue from patients with complications following transvaginal implantation of mesh is typified by a dense fibrous capsule with an immune-cell rich infiltrate suggesting that the host immune response has a role in transvaginal PPL mesh complications through the separate contributions of the host (patient), the biological niche within which the material is implanted, and biomaterial properties of the mesh. This immune response might be strongly influenced by both the baseline inflammatory status of the patient, surgical technique and experience, and the unique hormonal, immune and microbial tissue niche of the vagina. Mesh porosity, surface area and stiffness also might have an effect on the immune and tissue response to transvaginal mesh placement. Thus, a regulatory pathway is needed for mesh development that recognizes the roles of host and biological factors in driving the immune response to mesh alongside mandatory mesh registries and the longitudinal surveillance of patients.

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“…Although the mechanism of such post-surgical complications is poorly understood, recent studies in non-human primates have shown that such complications stem from undesirable and prolonged immune responses and may also be associated with decreased vaginal collagen, elastin, and smooth muscles [ 9 , 40 ]. Explanted meshes from women also suggested that sub-optimal meshes that lead to erosion and pain pique both the innate and adaptive immune systems of the body [ 19 , 118 ]. Furthermore, it is now becoming clear that even lightweight microporous stiff meshes are associated with exposures and erosions, with increased matrix metalloproteinase (MMP) activity, which leads to degradation of muscularis layer/smooth muscle content and an increase in the ratio of collagen subtypes III/I [ 42 , 45 ].…”

Section: Practical Considerations In the Design Of New-generation mentioning

confidence: 99%

Emerging Nano/Micro-Structured Degradable Polymeric Meshes for Pelvic Floor Reconstruction

et al. 2020

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Pelvic organ prolapse (POP) is a hidden women’s health disorder that impacts 1 in 4 women across all age groups. Surgical intervention has been the only treatment option, often involving non-degradable meshes, with variable results. However, recent reports have highlighted the adverse effects of meshes in the long term, which involve unacceptable rates of erosion, chronic infection and severe pain related to mesh shrinkage. Therefore, there is an urgent unmet need to fabricate of new class of biocompatible meshes for the treatment of POP. This review focuses on the causes for the downfall of commercial meshes, and discusses the use of emerging technologies such as electrospinning and 3D printing to design new meshes. Furthermore, we discuss the impact and advantage of nano-/microstructured alternative meshes over commercial meshes with respect to their tissue integration performance. Considering the key challenges of current meshes, we discuss the potential of cell-based tissue engineering strategies to augment the new class of meshes to improve biocompatibility and immunomodulation. Finally, this review highlights the future direction in designing the new class of mesh to overcome the hurdles of foreign body rejection faced by the traditional meshes, in order to have safe and effective treatment for women in the long term.

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Characterization of the T-Cell Response to Polypropylene Mesh in Women With Complications

Cited by 4 publications

References 0 publications

CD68+ macrophages as crucial components of the foreign body reaction demonstrate an unconventional pattern of functional markers quantified by analysis with double fluorescence staining

CD68+ macrophages as crucial components of the foreign body reaction demonstrate an unconventional pattern of functional markers quantified by analysis with double fluorescence staining

Host–biomaterial interactions in mesh complications after pelvic floor reconstructive surgery

Emerging Nano/Micro-Structured Degradable Polymeric Meshes for Pelvic Floor Reconstruction

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