Evaluation of a polyacrylamide hydrogel in the treatment of induced osteoarthritis in a goat model: a randomized controlled pilot study

Purpose: Polyacrylamide hydrogel (PAAG) is an inert, non-degradable, non-immunogenic polymer gel with high viscoelasticity consisting of 97.5% sterile water and 2.5% cross-linked polyacrylamide. Its biocompatibility in soft tissues has been demonstrated. PAAG has recently been tested for the treatment of osteoarthritis (OA) in horses with highly encouraging results; however no standardized experimental studies have been done to explore its efficacy. The purpose of this study was to evaluate PAAG in the treatment of induced OA in a goat model.

Methods: A randomized controlled study was conducted involving goats with induced OA on the left stifle (knee) joint. OA was surgically induced by the transection of the medial collateral ligament, the bisection of the medial meniscus at its midpoint and partial-thickness incisions of the cartilage of the medial tibial plateau. Goats were allowed free exercise, and 3 months after surgery they were randomly divided into 2 groups: group 1 (n = 4): PAAG and group 2 (n = 2): saline solution (control). Treatments were injected intraarticularly. MRI of the left knee had been performed prior to surgery, at the time of injection (3 months) and 4, 5 and 7 months post-surgery. T1, T2/PD and Stir weighted MRI images were used to assess OA. All goats were clinically evaluated on ground and on treadmill and videotaped for evaluation by 3 blinded observers. Haematology, biochemistry and acute phase proteins were also assessed. The goats were euthanized 7 months after surgery, and gross pathology and histopathology, including immunohistochemistry for nerve endings (n = 3 joints), were performed on both femorotibial joints. The hardness of the joint capsule was measured in both groups using Instron ® 5564 testing system (HIS GlobalSpec, MA, USA).

Results: At the end of the study, 75 % of the goats treated with PAAG were clinically sound, and 25 % of them had not improved, whereas the 2 control goats were still lame. In both groups, the values of haematology, biochemistry, or acute phase proteins were within normal range. MRI showed that in group one, 3 out of 4 goats had a decrease followed by a stabilization of OA lesions, while 1 goat had a mild progression of the OA lesions. In group 2, both goats had a mild or marked increase of OA lesions. Gross pathology inspection in group 1 demonstrated that all the operated knees showed typical signs of OA. The inner synovial lining was thickened, and the cartilage surface was uneven in all cases. The gel was seen in various amounts adhering to the inner side of the joint capsule in all the goats of group 1. Gross inspection of both goats in group 2 also showed cartilage lesions and synovial thickening, but the histopathological investigations revealed this to be more prominent in group 1 than in group 2. It comprised angiogenesis, collagen and synovial cell increase, and in the injected goats, also the gel. The nerve endings were normal looking and in normal numbers. The investigation of the joint capsule hardness showed that in the treated knee of the goats of group 1, the medial side (injected with PAAG) was always less hard than the lateral side.

Conclusions: This study demonstrated the efficacy of a novel treatment of OA, with 75 % of the goats treated with PAAG being clinically sound. Treatment with PAAG did not have any influence on haematology, biochemistry, or acute phase proteins. It induced a moderate synovial hyperplasia of the inner side of the capsule with trapped (integrated) gel, increased angiogenesis and collagen production. Preliminary pathology and joint capsule hardness data suggest that PAAG might act mainly on the joint soft tissue and especially the synovial membrane. PAAG might have 2 effects on OA joints: 1- Joint capsule was less hard on the treated (medial) than on the non-treated (lateral) side and had a lower hardness when compared to group 2. OA joints typically show joint stiffness - a major source of pain in OA. By decreasing the joint capsule hardness, and thus joint stiffness, PAAG might relieve the pain in the OA joint (“disease-modifying” effect). 2- MRI and pathology investigations have revealed a stabilization of OA lesions in the goats of group 1, which might be explained by the mechanical effect through the high viscosupplementation provided by PAAG that was still present in the joint cavity (“disease-stabilizing” effect). No adverse reaction was seen following intraarticular injection of PAAG. More investigations are needed to fully understand the mechanism of action of PAAG in improving clinical signs and in stabilizing OA. This pilot study may be used as a basis for further studies using larger animal numbers.