Sulfasalazine Resolves Joint Stiffness in a Rabbit Model of Arthrofibrosis

Area of Science:

• Orthopaedic Research
• Cell Biology
• Pharmacology

Background:

• Joint stiffness from fibrosis/capsule contracture is a disabling complication of articular injury.
• Surgical interventions often fail to fully resolve this condition.
• Myofibroblasts, responsible for excessive collagen production and matrix contraction, are key contributors to fibrosis.

Purpose of the Study:

• To investigate the efficacy of intra-articular drugs targeting myofibroblast survival and collagen production in reducing joint stiffness in a rabbit model.
• To evaluate the safety of these drugs concerning cruciate ligament laxity.

Main Methods:

• Drugs (sulfasalazine, β-aminopropionitrile, cis-hydroxyproline) were encapsulated in poly[lactic-co-glycolic] acid pellets and implanted in rabbit joints post-fibrosis induction.
• Joint stiffness was measured using flexion-extension testing.
• Capsule α-smooth muscle actin (α-SMA) expression, intimal thickness, and fibroblast contractile activity were assessed.

Main Results:

• Sulfasalazine significantly reduced joint stiffness compared to controls (p=0.0065).
• None of the tested drugs induced significant cruciate ligament laxity.
• Sulfasalazine and β-aminopropionitrile inhibited fibroblast contractile activity in vitro, and sulfasalazine reduced α-SMA expression and intimal thickness in vivo.

Conclusions:

• Intra-articular sulfasalazine effectively reduces established joint stiffness in a rabbit model, likely by clearing myofibroblasts.
• These findings provide proof-of-concept for a non-surgical approach to resolving joint stiffness due to fibrosis.