In a new study researchers have shown 2.5% injectable polyacrylamide hydrogel (iPAAG) injected into the joints causes a beneficial type of inflammation horses need for long-term relief from osteoarthritis, while providing bioscaffolding that might support healthy tissue regeneration.

The mild, microscopic-level inflammation lasts about 14 days after injection and appears to stimulate the immune system, which might help horses fight the degenerative disease process. The bioscaffolding, meanwhile, develops inside the synovial membrane (joint lining) as the tissue fully absorbs the drug-free gel, said Jason Lowe, MBA, BVSc, Cert EP, managing partner at Innovative Medical Solutions Vet, in Cambridge, New Zealand.

“In biology, there’s good inflammation and bad inflammation,” Lowe said. “Good inflammation is part of the body’s natural immune response. So, if we’re supporting the body’s natural immune response with products like this gel, we’re creating the environment for healing naturally.” This is in stark contrast to cortisone that artificially suppresses the immune response, he added.

While investigators on recent studies have shown that iPAAG injections seem to improve lameness in horses with osteoarthritis, experts still don’t understand exactly what is happening inside the joints on a microscopic level, Lowe said.

He and his fellow researchers injected 13 fetlock or central knee joints in 10 healthy Thoroughbreds with 2.5% synthetic cross-linked polyacrylamide gel at a dose of either 50 or 100 milligrams. These horses were 3 to 5 years old and had no signs of joint disease. For later comparison they aspirated synovial fluid from seven of the horses’ joints before injecting them.

The researchers examined each injected joint immediately after treatment and again either 14, 42, or 90 days later. During these exams the researchers aspirated synovial fluid for analysis. They euthanized four of the horses—two at Day 14 and two at Day 42—for more detailed tissue sample analyses, including microscopic examination. They also examined untreated opposite limbs in the euthanized horses.

All horses appeared normal during physical exams post-injection, with no lameness or obvious swelling, regardless of the dose. The researchers found no visible changes in the joints during dissection and no remaining free gel. They also found the synovial fluid cellular makeup was normal, except for a significant increase in macrophages, which are immune cells designed to “eat” foreign materials and debris, by Day 14.

In further analyses the researchers saw a microscopic inflammatory reaction, with swelling of protruding structures called the villi, filling with more macrophages. They also noticed more blood vessels in treated than untreated joints.

Future Implications for 2.5% iPAAG Use in Horses

Lowe said findings suggest the effects of the 2.5% gel aren’t merely mechanical—making joint structures slide more smoothly across each other—but are triggering a natural healing effect. Regarding synovial membrane inflammation, he explained, “it’s recruiting more synovial tissue macrophages—bringing in more firemen to fight the fire.”

As for the gel itself, the scientists found it had integrated fully and extensively into the joint tissue, creating 3D structures resembling scaffolds within 14 days of injection, he said. The numerous macrophages did not actually consume the hydrogel, meaning the product could remain in place as bioscaffolding, he added, for potentially rebuilding healthy tissues in the joint that might last for years.

Overall, the results show the injections provoked a minimal and nonirritating immune response that is the body’s typical reaction to a foreign substance, Lowe said. The researchers saw no signs of infection or of tissue toughening, hardening, or scarring. “This is just an incredibly safe product,” he said.

While the inflammation is minor, Lowe said he nonetheless recommends dialing back the exercise for horses treated with 2.5% iPAAG during that two-week process, with more emphasis on swimming, walking, and general rehabilitation. “You can keep them fit,” he said. “Just back them off a bit to give the body the chance to do what it needs to do.”

In addition, Lowe said the findings suggest the gel could be particularly beneficial to senior horses. That’s because it could safely help with arthritic pain without the insulin-related risks associated with steroid injections. “The beauty of it is that it’s nonpharmacological,” he said.

Editor’s note: The authors declared the research—which received funding from Innovative Medical Solutions (IMS) Ltd, the Market Authorization Holder for 2.5 iPAAG (ArthramidVet) in Australia and New Zealand—was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. See the full study and its disclosures in the study, Histologic and cytologic changes in normal equine joints after injection with 2.5% injectable polyacrylamide hydrogel reveal low-level macrophage-driven foreign body response, which appeared in the Journal of the American Veterinary Medical Association in February 2024.