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

Abstract

Polypropylene (PPL) mesh is widely used in pelvic floor reconstructive surgery for prolapse and stress urinary incontinence. However, some women, particularly those 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, as well as mandatory mesh registries and the longitudinal surveillance of patients.

Key points

  • Current evidence suggests that risk factors for developing complications following transvaginal mesh placement include pro-inflammatory conditions such as patient age, smoking and diabetes, as well as surgical technique and experience.

  • Explanted mesh following transvaginal pelvic organ prolapse repair from women with complications shows poorly regulated inflammation with a fibrous capsule and a dense cellular infiltrate of predominantly macrophages.

  • Differences in the abdominal and vaginal biological niche probably contribute to dissimilar immune responses to polypropylene mesh and consequently the extent to which mesh can integrate.

  • Mesh with large pore diameters, low surface area and low local stiffness might be less likely to induce an adverse foreign body response, but this supposition has not been evaluated longitudinally.

  • A lack of transparency in pelvic floor preclinical testing and post-marketing surveillance are regulatory failings that have probably contributed to the inappropriate repurposing of meshes for some patient groups.

  • The ability to assess factors driving negative outcomes will rely on longitudinal studies to ascertain baseline drivers of tissue response in women who develop complications and those who do not.

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Fig. 1: The host immune response to PPL mesh cumulating in a foreign body reaction.
Fig. 2: Polypropylene material properties and processes that could influence the host immune response.
Fig. 3: Regulated inflammation and mesh complications are influenced by the complex interaction between the patient (host factors), tissue niche and mesh material properties.

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R.E.A., H.L.M. and S.J.B.S. researched data for the article, R.E.A., M.L.I.-K., R.C. and S.J.B.S. made substantial contributions to the discussion of the content of the article, R.E.A., M.I., H.L.M. and S.S. wrote the article, R.E.A., M.I., H.L.M., R.C. and S.S. reviewed/edited the manuscript before submission.

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Correspondence to Roxanna E. Abhari.

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Glossary

Biocompatible

Biocompatibility is the ability of a material to perform its intended function with an appropriate host immune response for a specific application.

Microporous meshes

According to the widely used Amid classification, microporous mesh refers to mesh that contains pores that are <10 microns in size.

M1 macrophages

Classically activated macrophages typically associated with pro-inflammatory responses in in vitro studies.

M2 macrophages

Alternatively activated macrophages that typically induce pro-resolving and anti-inflammatory responses in in vitro studies.

TH1 cytokines

For example, IFNγ and TNF are typically associated with pro-inflammatory responses driving immune cell activation and maturation.

Vroman effect

The sequence in which serum proteins adsorb to a surface; proteins that adsorb earlier are competitively displaced by other proteins with stronger binding affinities.

Mesh knot

Refers to a dense area of mesh fibres immediately adjacent to each other.

510k route

Refers to a premarket submission process made to the FDA, demonstrating that the device that is to be marketed is as safe and effective (that is, substantially equivalent) to a legally marketed device.

Predicate device

A medical device that is used as a point of comparison for new medical devices seeking approval through the FDA’s 510k premarket clearance pathway.

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Abhari, R.E., Izett-Kay, M.L., Morris, H.L. et al. Host–biomaterial interactions in mesh complications after pelvic floor reconstructive surgery. Nat Rev Urol 18, 725–738 (2021). https://doi.org/10.1038/s41585-021-00511-y

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