Host response to synthetic mesh in women with mesh complications.
Despite good anatomic and functional outcomes, urogynecologic polypropylene meshes that are used to treat pelvic organ prolapse and stress urinary incontinence are associated with significant complications, most commonly mesh exposure and pain. Few studies have been performed that specifically focus on the host response to urogynecologic meshes. The macrophage has long been known to be the key cell type that mediates the foreign body response. Conceptually, macrophages that respond to a foreign body can be dichotomized broadly into M1 proinflammatory and M2 proremodeling subtypes. A prolonged M1 response is thought to result in chronic inflammation and the formation of foreign body giant cells with potential for ongoing tissue damage and destruction. Although a limited M2 predominant response is favorable for tissue integration and ingrowth, excessive M2 activity can lead to accelerated fibrillar matrix deposition and result in fibrosis and encapsulation of the mesh.



The purpose of this study was to define and compare the macrophage response in patients who undergo mesh excision surgery for the indication of pain vs a mesh exposure.



Patients who were scheduled to undergo a surgical excision of mesh for pain or exposure at Magee-Womens Hospital were offered enrollment. Twenty-seven mesh-vagina complexes that were removed for the primary complaint of a mesh exposure (n = 15) vs pain in the absence of an exposure (n = 12) were compared with 30 full-thickness vaginal biopsy specimens from women who underwent benign gynecologic surgery without mesh. Macrophage M1 proinflammatory vs M2 proremodeling phenotypes were examined via immunofluorescent labeling for cell surface markers CD86 (M1) vs CD206 (M2) and M1 vs M2 cytokines via enzyme-linked immunosorbent assay. The amount of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) proteolytic enzymes were quantified by zymography and substrate degradation assays, as an indication of tissue matrix degradation. Statistics were performed with the use of 1-way analysis of variance with appropriate post hoc tests, t-tests, and Fisher's Exact test.



Twenty-seven mesh-vaginal tissue complexes were excised from 27 different women with mesh complications: 15 incontinence mid urethral slings and 12 prolapse meshes. On histologic examination, macrophages surrounded each mesh fiber in both groups, with predominance of the M1 subtype. M1 and M2 cytokines/chemokines, MMP-9 (pro- and active), and MMP-2 (active) were increased significantly in mesh-vagina explants, as compared with vagina without mesh. Mesh explants that were removed for exposure had 88.4% higher pro-MMP-9 (P = .035) than those removed for pain. A positive correlation was observed between the profibrotic cytokine interleukin-10 and the percentage of M2 cells (r = 0.697; P = .037) in the pain group.



In women with complications, mesh induces a proinflammatory response that persists years after implantation. The increase in MMP-9 in mesh explants that were removed for exposure indicates degradation; the positive association between interleukin-10 and M2 macrophages in mesh explants that are removed for pain is consistent with fibrosis.
Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA.
Alexis L
AL
Nolfi
Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA.
Bryan N
BN
Brown
Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA; Department of Obstetrics, Gynecology, and Reproductive Sciences, School of Medicine, University of Pittsburgh, Pittsburgh, PA.
Rui
R
Liang
Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA.
Stacy L
SL
Palcsey
Department of Obstetrics, Gynecology, and Reproductive Sciences, School of Medicine, University of Pittsburgh, Pittsburgh, PA.
Michael J
MJ
Bonidie
Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA.
Steven D
SD
Abramowitch
Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA; Department of Obstetrics, Gynecology, and Reproductive Sciences, School of Medicine, University of Pittsburgh, Pittsburgh, PA. Electronic address: pmoalli@mail.magee.edu.
Pamela A
PA
Moalli
D000328:Adult; D005260:Female; D013509:Gynecologic Surgical Procedures / Q000009:adverse effects*; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D056887:Pelvic Organ Prolapse / Q000378:metabolism / Q000601:surgery*; D013526:Surgical Mesh / Q000009:adverse effects*; D014550:Urinary Incontinence, Stress / Q000378:metabolism / Q000601:surgery*; D014621:Vagina / Q000378:metabolism* / Q000601:surgery
D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
cytokine; inflammatory response; macrophage phenotype; polypropylene mesh