Non-Titanised Compared to Titanised Polypropylene Meshes Induce a Pro-Inflammatory and Anti-Angiogenic Response in Fibroblast Co-Cultures

Abstract

Pelvic organs prolapse (POP) can be treated surgically with native tissue or by placing mesh implants in the pelvic floor and vaginal wall. Mesh implants are manufactured from different materials. We previously demonstrated that titanised polypropylene meshes induced different macrophage polarization compared to pure polypropylene meshes. However, these differences were only observed in cell cultures where the meshes were encapsulated by human dermal fibroblasts (NHDF). In this study, we co-cultivated titanised and non-titanised polypropylene meshes with NHDF alone to analyze the immune response of NHDF against different mesh materials. Concentration of proteins in cell culture supernatants were analyzed using multiplex ELISA. We identified a significant increase of VEGF and VEGF-C ( p = 0.001) for both meshes, and the polypropylene meshes induced significant ( p < 0.001) upregulation of sFlt-1, a vascularization inhibitor. Titanised meshes significantly downregulated ( p = 0.034) the pro-inflammatory cytokine IL-16, whereas polypropylene meshes showed no effect on IL-16. Polypropylene meshes significantly reduced ( p = 0.011) the anti-inflammatory cytokine IL-4, while titanised meshes had no effect on IL-4. Polypropylene meshes induce an anti-angiogenic (sFlt-1 upregulation) and pro-inflammatory response. Titanised coating of polypropylene implants reduced proinflammatory cytokines and promoted angiogenesis. These findings have important clinical implications for the postoperative period where fibroblasts play a key role.

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