Vascular remodelling and fibrotic changes in the joint capsule during periprosthetic knee infections

Aims Periprosthetic joint infection (PJI) represents one of the most severe complications following joint arthroplasty, often associated with a high recurrence rate despite appropriate therapeutic interventions. The underlying mechanisms contributing to this persistent risk remain incompletely understood. We hypothesize that alterations in joint capsule vascularization and fibrotic remodelling contribute to the pathophysiology of PJI and its recurrence. Methods A total of 69 patients undergoing joint arthroplasty surgery were included in the study (21 controls: primary total knee arthroplasty (TKA), 22 PJI revision: explantation, and 26 PJI revision: prosthesis reimplantation after temporary arthrodesis). Each knee joint capsule specimen was analyzed using haematoxylin and eosin (HE) staining, Masson’s trichrome, Sirius red staining, immunofluorescence staining, and real-time quantitative polymerase chain reaction (RT-qPCR). Results Mean vessel area, diameter, and perimeter were reduced in PJI specimens, despite an overall increase in the number of blood vessels. A significant reduction in smooth muscle cell (SMC) and pericyte layer thickness, along with decreased pericyte coverage of vessel walls, was observed following both explantation and reimplantation. Fibrotic remodelling, indicated by increased collagen deposition, was markedly elevated in PJI samples at both stages. Gene expression analysis revealed upregulation of PDGFB, MIG, MMP-9, and COL1A1 at explantation or reimplantation, while PDGFA and FN1 were downregulated at explantation and significantly upregulated at reimplantation. VEGFA and FGF-2 expression remained consistently suppressed. Conclusion PJI is associated with profound vascular remodelling and fibrotic transformation of the joint capsule, marked by aberrant angiogenesis, disrupted vessel architecture, and distinct gene expression profiles. These alterations may impair tissue perfusion, compromise immune surveillance, and hinder antibiotic delivery, thereby contributing to recurrent infection. Targeting soft-tissue vascularization and fibrosis may represent a novel therapeutic strategy to reduce PJI recurrence and enhance surgical outcomes. Cite this article: Bone Joint Res 2026;15(2):121–134.