Pathophysiology of Arthrofibrosis After Total Knee Arthroplasty: Current Concepts and Future Directions

Abstract

Arthrofibrosis is a common complication following total knee arthroplasty (TKA), characterized by excessive fibrous tissue formation within the joint, leading to restricted range of motion, pain, and functional limitations. This review focuses on three key areas: (1) dysregulated wound healing processes and molecular risk factors; (2) histopathological and immunohistochemical features; and (3) emerging molecular targets and potential personalized treatment strategies. Dysregulated wound healing after TKA leads to persistent fibroblast and myofibroblast activation, excessive extracellular matrix deposition, and joint capsule contracture. Key molecular mediators, such as transforming growth factor-β 1 (TGF-β1), xylosyltransferase-I (XT-I), and β-catenin (β-catenin), drive these processes, exacerbating fibrosis. Genetic predisposition, inflammatory signaling, and immune cell infiltration further contribute to the progression of arthrofibrosis. Histopathologically, arthrofibrotic tissue shows increased collagen types I and III deposition, along with upregulated markers such as α-smooth muscle actin and TGF-β1 receptor 1, reflecting myofibroblast activation and inflammation. Immunohistochemical analysis reveals abundant CD68+ macrophages and T cell infiltration, supporting the inflammatory microenvironment. Recent advances in molecular profiling have identified potential biomarkers and therapeutic targets, including bromodomain-containing protein 4 and XT-I, offering hope for personalized medicine. Despite promising preclinical findings, clinical translation remains in its early stages. Future research should prioritize the validation of these biomarkers and explore genetic and epigenetic stratification to improve management and outcomes for high-risk patients.

Keywords

arthrofibrosis - TKA - pathophysiology

Publication History

Received: 02 November 2025

Accepted: 25 November 2025

Accepted Manuscript online:
27 November 2025

Article published online:
17 December 2025

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