Failure of the physiological resolution of the foreign body response as a mechanism for persistent multisystem manifestations following polypropylene mesh implantation: a mechanistic hypothesis

Polypropylene mesh implantation elicits a foreign-body response that usually progresses toward tissue integration and long-term tolerance. However, a minority of recipients report persistent local or multisystem manifestations whose biological basis remains uncertain. We propose that the central event in these patients may not be persistent inflammation itself, but impaired physiological resolution of the foreign-body response. In this model, defective resolution is characterized by incomplete clearance of inflammatory cells, impaired efferocytosis, sustained macrophage activation, imbalance between pro-inflammatory and pro-resolving mediators, and ongoing extracellular-matrix remodeling, resulting in a biologically active peri-implant niche. This local phenotype may interact with host susceptibility and activate alternative or complementary amplification pathways, including trained immunity, immunometabolic adaptation, extracellular-vesicle signaling, and neuroimmune signaling. These mechanisms are not assumed to occur sequentially or in all patients, and their specific contribution after polypropylene mesh implantation remains unproven. The hypothesis can be tested by comparing symptomatic and asymptomatic mesh recipients using local tissue analysis, circulating biomarkers, longitudinal sampling, and integrative molecular profiling. Persistent inflammation in the presence of preserved pro-resolving mechanisms would weaken the model. This framework therefore provides a falsifiable approach for investigating biological heterogeneity after mesh implantation and for distinguishing impaired resolution from chronic inflammation alone.