Profiling the T cell response to polypropylene mesh in a non-human primate sacrocolpopexy model

Polypropylene mesh (PPM) improves anatomic outcomes in pelvic organ prolapse (POP) repair, yet complications-most commonly pain and mesh exposure-occur in ∼10 % of cases. Clinically, meshes that are implanted flat often demonstrate striking deformation at explanation, including pore collapse and wrinkling. Both computational models and in vivo studies confirm that mesh geometry changes substantially after tensioning during prolapse repair. Although T cells have been implicated in mesh-related complications, the specific impact of mesh deformation on adaptive immunity is not fully understood. To address this gap, a lightweight PPM (Restorelle) was implanted in nonhuman primates either in its flat configuration (stable, R0) or engineered into two progressively deformed geometries: R45 (unstable: pore collapsed) and RD (predeformed: pore collapsed + wrinkled). Sham-operated animals served as controls. Twelve weeks post-implantation, mesh-tissue complexes were analyzed to quantify T-cell phenotypes, tissue remodeling, and downstream healing outcomes. Findings were integrated with a comparative proteomic analysis of flat versus deformed human mesh explants. Mesh burden increased stepwise with deformation (R0 < R45 < RD). Deformation amplified T-cell infiltration within the vaginal adventitia, with helper T cells dominating and cytotoxic T cells contributing minimally. T_regs were enriched in the moderately deformed R45 group-consistent with injury resolution-but were markedly reduced in RD, indicating a shift toward chronic, non-resolving inflammation. Whereas flat meshes maintained organized collagen and physiologic fibrotic encapsulation, deformed meshes-particularly RD-exhibited loss of organized ECM, increased fibroblast-driven remodeling, and elevated fibroblast growth factor-2 (FGF-2). Cytokine profiling revealed increased IL-1β and CXCL12 across all mesh groups, but RD uniquely showed suppression of Th2 cytokines (IL-4, IL-5), a signature of impaired immune resolution. Human explants mirrored key primate findings: CD99, a marker of T-cell trafficking and persistent activation, was elevated in specimens from patients with complications, while CD84, which mediates T:B-cell interactions and memory formation, was reduced-suggesting repetitive T-cell activation without durable immune regulation. Together, these results demonstrate that increasing mesh deformation drives a shift from a Th2/Treg-dominant, pro-resolution immune response toward chronic inflammation characterized by persistent T-cell activation and fibroblast-mediated ECM disruption. This work directly links mesh geometry-induced mechanical stress to adaptive immune dysregulation and disordered collagen remodeling and validates these signatures in human specimens. The findings highlight actionable opportunities for geometry-preserving mesh designs and targeted T-cell-directed immunomodulation to prevent complications.