Arthrofibrosis After Total Knee Arthroplasty: Insight Into Molecular Mechanism

Knee stiffness is a disabling condition that can affect 3% to 4% of patients undergoing total knee arthroplasty. Although a number of factors are known to result in this undesirable complication, stiffness after knee arthroplasty can develop in patients for whom no “identifiable” cause exists. The cause of “idiopathic” stiffness after knee arthroplasty remains elusive. This study represents the findings of a series of molecular studies performed on periarticular tissue samples retrieved from patients with arthrofibrosis undergoing revision surgery. We have demonstrated that activation of inflammatory cells results in the production of reactive oxygen and nitrogen species (RONS) such as superoxide anion, H₂O₂, hypochlorous acid/chlorine gas (HOCl/Cl₂), and nitric oxide. These products can in turn lead to the breakdown and disorganization of periarticular proteins, in particular collagen. We have also shown that extensive scar formation around the knee joint is initiated and propagated, at least in part, by the release of ROS products in susceptible patients. Some individuals with a deficiency in the degradation pathway or others with exaggerated production, all leading to relative abundance of ROS, are at risk of aggressive scar formation during tissue repair that can lead to stiffness after knee surgery. A series of preliminary genetic studies have been performed to identify potential biomarkers. We believe understanding the molecular mechanism of arthrofibrosis can lead to design and administration of treatment protocols, aimed at reducing ROS accumulation, that can potentially minimize or prevent this undesirable complication.