Stiffness: Prevention and Treatment

Introduction

Motion loss after anterior cruciate ligament (ACL) reconstruction is a devastating complication that can compromise the patient’s ability to return to normal activity. It is a common complication of multiligament knee surgery but can also occur in the setting of isolated ACL reconstruction. An isolated cause of stiffness can sometimes be identified, but in many cases it is a combination of factors both mechanical and biologic. Arthrofibrosis occurs when fibrous cells proliferate in response to hemarthrosis caused by injury or surgery. This, in isolation or in combination with mechanical factors such as improper graft placement, can lead to severe stiffness and disability.

Etiology

The incidence of arthrofibrosis after ACL reconstruction reportedly ranges from 4% to 35%. It is more common when surgery is performed in the acute setting, less than 3 weeks after injury. A history of arthrofibrosis from previous surgery or trauma should alert the surgeon. The exact reason behind this excessive connective tissue proliferation is not known. Several mechanisms have been proposed. Two cytokines, the platelet-derived growth factor-β (PDGF-β) and the transforming growth factor-β (TGF-β), play a central role in the healing process. Further expression of TGF-β has been associated with unresolved inflammation and fibrotic events. In animal models, the neutralization of its isoforms (TGFβ-1 and TGFβ-2) has reduced scarring. A possible association between arthrofibrosis and certain human leukocyte antigen (HLA) types has been suggested. Skutek et al. performed HLA typing in a pool of patients who developed primary arthrofibrosis following ACL reconstruction. Patients with secondary reasons for arthrofibrosis, such as prolonged immobilization, infection, or other surgical complications, were excluded. In their patient group, the phenotype HLA-Cw∗08 was detected significantly more often, compared with the control group. Additionally, in the same group of patients, the phenotype’s HLA-Cw∗07 and HLA-DQB1 were detected significantly less frequently compared with the control group. The importance of the fat pad in the fibrotic process following surgical trauma to the knee has long been recognized. Adipose tissue is capable of releasing cytokines in an endocrine, autocrine, and paracrine manner. Ushiyama et al. demonstrated that the infrapatellar fat pad produces a variety of growth factors and proinflammatory cytokines such as basic fibroblast growth factor, vascular endothelial growth factor, tumor necrosis factor alpha, and interleukin 6, much like an endocrine organ. Additionally, Murukami et al. found elevated concentrations of PDGF-β and TGF-β in the fat pad after ACL reconstruction. From this research, it is evident that the knee fat pad is capable of mounting a response much like the articular synovium and enhances the inflammatory reaction to the surgical insult. Preservation and minimal disturbance of this structure during ACL reconstruction may minimize excessive scarring and motion loss.

More recently, efforts have been focused on determining whether blockade of some of these cytokines could actually prevent arthrofibrosis. A novel monoclonal antibody against vascular endothelial growth factors has been shown to have a dose dependent response in the reduction of arthrofibrosis in the animal model. In another study, gene delivery of TGFβ-1 was found to induce arthrofibrosis and chondral metaplasia of the synovium in vivo in rats. Therefore one might postulate that biologics developed to antagonize TGFβ-1 could also be useful in the prevention of arthrofibrosis.