¹Charité Universitätsmedizin, Berlin, Deutschland

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Objectives and questions: Reinfection risk remains significantly elevated after periprosthetic joint infection (PJI) of the knee, yet the underlying mechanisms are poorly understood. The prevailing assumption that bone and soft tissues recover post-explant revision surgery has been challenged by evidence suggesting persistent pathological changes. This study evaluates whether alterations in soft tissue vascularization and fibrosis contribute to PJI pathology and the heightened reinfection risk.

Material and methods: Soft tissue samples were analyzed from 65 patients undergoing joint replacement surgery, including those with primary knee osteoarthritis (control, n=19) and those undergoing two-stage surgical interventions for PJI (explantation, n=20; reimplantation, n=26). Histological assessment measured vessel count, density, and fibrosis (Sirius red, Masson). Immunohistochemical staining evaluated cell proliferation. Molecular analyses quantified angiogenesis-related gene expression (PDGFB, MIG, MMP9, HIF-1A, ANGPT-2, VEGFA, PDGFA, FN1, FGF2) and endothelial markers (MMP-2, PECAM-1) using PCR.

Results: PJI samples showed significant vascular and fibrotic changes. Vessel number and density were elevated at explantation (+29.6% and +42.2%) and reimplantation (+58.4% and +41.4%). Cell proliferation rates increased (+32.6% at explantation, +42.9% at reimplantation). Fibrosis was significantly increased at explantation (mean diff. -19.15, p=0.0053) and reimplantation (mean diff. -21.10, p=0.0014). PDGFB expression increased at reimplantation (2.47-fold), MIG at both explantation (5.74-fold) and reimplantation (3.70-fold), MMP9 at explantation (2.34-fold) and reimplantation (6.67-fold). HIF-1A and ANGPT-2 increased modestly, VEGFA, PDGFA, FN1, and FGF2 decreased. No significant changes in MMP-2 or PECAM-1.

Discussion and conclusions: These findings highlight vascular and fibrotic remodeling in infected periprosthetic soft tissues. Increased vessel density, fibrosis, and angiogenesis-related changes create a microenvironment favoring reinfection. We postulate that concurrent vascularization and fibrosis impair immune surveillance, promoting reinfection despite surgical intervention.