A Look at the Cellular Changes in Equine Joints With 2.5% PAAG 

Researchers characterized 2.5% PAAG's synovial integration process to develop a safety profile.
Horse carpal joint injection with 2.5% PAAG
In this study, researchers injected 2.5% PAAG into horses’ fetlock and middle carpal joints, with the opposite limb serving as the untreated control. | Adobe Stock

Studies on 2.5% polyacrylamide gel (PAAG) for joint injections so far indicate it’s safe to use, does not cause fibrosis or granuloma formation, and does not leave free gel within the joint space. Nonseptic flare reactions are rare (0.04%) and predominantly driven by macrophage responses. 

2.5% PAAG Study Population

At the 2024 American Association of Equine Practitioners Convention, Jason Lowe, BVSc, Cert EP, MBA, described a study aiming to characterize PAAG’s synovial integration process so as to develop a safety profile. The study included 10 retired Thoroughbreds without osteoarthritis, aged 3-5 years. Researchers injected either 50 or 100 mg of 2.5% PAAG into the fetlock and middle carpal joints, with the opposite limb serving as an untreated control. They collected samples at either 14 or 42 days and from one horse at 90 days. 

The researchers evaluated the horses with clinical and lameness exams, measured effusion and synoviocentesis samples, and assessed horses’ reactions to flexion. They then conducted postmortem examinations, along with histology and scanning electron microscopy. 

Study Results

Lowe reported no adverse events at any time during the study. The results show: 

  • The gross postmortem exam confirmed no free gel in the synovial space. 
  • Synoviocentesis samples were all within normal laboratory limits throughout 42 days. 

The researchers noted a transient increase in total nucleated cell count—predominantly mononuclear cells—compared to controls. Lowe explained that macrophage infiltration occurs with an injection, and these cells treat the gel like a foreign body. Yet, the gel molecules are so large that without being able to encompass it, the initial influx of macrophages is transient; they become quiescent, die off, or move away. 

  • On histology, the gel is integrated into the superficial subintima. No gel was found overlying the synovium (i.e., there was no free gel in the joint cavity). Villous hypertrophy was noted. However, following a transient process of initial bulking of tissues, the gel is incorporated into the tissue. 
  • Scanning electron microscopy shows that over 14 days, the gel becomes fully integrated with the collagen fibers and cells coming in and the blood vessels from around the gel structure, with the gel being “planted” into the synovium. 

Lowe said the results of this study are encouraging for 2.5% PAAG’s safety profile.  

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