Characterization of the host inflammatory response following implantation of prolapse mesh in rhesus macaque

Abstract

Objective To determine the predominant cell type (macrophage, T-lymphocyte, B-lymphocyte, mast cell) within the area of implantation of the prototypical polypropylene mesh, Gynemesh PS (Ethicon); and to determine the phenotypic profile (M1 pro-inflammatory, M2 anti-inflammatory) of the macrophage response to three different polypropylene meshes: Gynemesh PS (Ethicon), and two lower weight, higher porosity meshes, UltraPro (Ethicon) and Restorelle (Coloplast). Study Design Sacrocolpopexy was performed following hysterectomy in rhesus macaques. Sham-operated animals served as controls. At 12 weeks post-surgery, the vagina-mesh complex was excised and the host inflammatory response was evaluated. Hematoxylin and eosin was used to perform routine histomorphologic evaluation. Identification of leukocyte (CD45+) subsets was performed by immunolabeling for CD68 (macrophage), CD3 (T-lymphocyte), CD20 (B-lymphocyte), and CD117 (mast cell). M1 and M2 macrophage subsets were identified using immunolabeling (CD86+ and CD206+, respectively), and further evaluation was performed using ELISA for two M1 (TNF-α and IL-12) and two M2 (IL-4 and IL-10) cytokines. Results Histomorphologic evaluation showed a dense cellular response surrounding each mesh fiber. CD45+ leukocytes accounted for 21.4±5.4% of total cells within the peri-mesh area captured in a 20× field, with macrophages as the predominant luekocyte subset (10.5±3.9% of total cells) followed by T-lymphocytes (7.3±1.7%), B-lymphocytes (3.0±1.2%), and mast cells (0.2±0.2%). The response was observed to be more diffuse with increasing distance from the fiber surface. Few leukocytes of any type were observed in sham-operated animals. Immunolabeling revealed polarization of the macrophage response towards the M1 phenotype in all mesh groups. However, the ratio of M2:M1 macrophages was increased in the fiber area in UltraPro (P=0.033) and Restorelle (P=0.016) compared to Gynemesh PS. In addition, a shift towards increased expression of the anti-inflammatory cytokine IL-10 was observed in Restorelle as compared to Gynemesh PS (P=0.011). Conclusions The host response to mesh consists predominantly of activated, pro-inflammatory, M1 macrophages at 12 weeks post-surgery. However, this response is attenuated with implantation of lighter weight, higher porosity mesh. While additional work is required to establish causal relationships, these results suggest a link between the host inflammatory response, mesh textile properties, and clinical outcomes in the repair of pelvic organ prolapse.

Shifts in macrophage phenotype at the biomaterial interface via IL-4 eluting coatings are associated with improved implant integration

“…However, we note that recent published studies have demonstrated that density of the mesh is a local driver of the host macrophage response, where increased local mesh density is associated with an increased local pro-inflammatory response [30, 31]. While investigation of the differences in the host response between fibers and knots was beyond the scope of the present study, it will be important to evaluate the effects of IL-4 coated mesh knots in order to illustrate the effects in the host response of the released IL-4 and the coating in the presence of high density and complex geometry of the implant.…”

“…These materials have recently been shown to elicit a predominantly M1 type response which is associated with the potential for tissue degradation and downstream complications when unresolved [30, 31]. Macrophage modulation only in early-stages of the host response, but also localized to the tissue-implant interface was sought in the present study, representing an advantage over strategies promoting non-local and/or extended shifts in the host response as it limits the potential for adverse long-term interactions and exacerbation of conditions which may exist at distant sites.…”

The Design of a Randomized Trial of Vaginal Surgery for Uterovaginal Prolapse: Vaginal Hysterectomy With Native Tissue Vault Suspension Versus Mesh Hysteropexy Suspension (The Study of Uterine Prolapse Procedures Randomized Trial)

“…Meshes with these characteristics have been shown to have less of a negative impact on the vagina in a primate model than their heavier weight, less porous counterparts. 22–24 Second, all additional prolapse repairs performed in this trial will be native tissue further minimizing possible mesh-load and possible mesh-related complications…”

Comparación in vitro de la citocompatibilidad entre los biomateriales fibroína y polipropileno

“…In a study conducted in Macacus rhesus, the post-implant inflammatory response to prolapse was characterized, elucidating the presence of proinflammatory cells after the PP mesh implantation [22]; in this study, the cellular immune response generated by the polypropylene mesh showed a predominance of proinflammatory cells type M1 macrophages within a few weeks of the surgical procedure; the researchers also found other proinflammatory cells to a lesser extent, such as CD45 (panleucocytes) that were distributed in the interstitium between the PP mesh and the host tissue, in addition to CD68-type macrophages that were widely distributed in each fiber of the mesh, while other cells were distributed in the periphery of its surface [22]. Several researchers have studied the post implantation effect with various polymeric materials, and have consistently observed the presence of inflammatory cells in polypropylene mesh tissue samples up to 8 years after their implantation; other researchers have observed the degradation of this material after implantation in humans [20].…”