Background/Purpose:

Chitosan, a glucosamine polysaccharide, is a good candidate for viscosupplementation in OA joints. Herein, we report the physico-chemical properties and the effects of an innovative chitosan hydrogels in the rabbit anterior cruciate ligament model ACLT model of OA.

Methods:

The mechanical and rheological properties of animal-free ultrapure chitosan hydrogels (Vegetech inside™, Synolyne Pharma, Belgium) were characterized using a mechanical compression equipment (Instron, US) and the Discovery Hybrid DHR-2 rheometer (TA Instruments, US). The properties were compared with those of synovial fluids and of hyaluronan: injection force, capacity to absorb shocks at walk frequency, ability to lubricate (viscosity at rest), and biodegradation kinetics. In addition, the chitosan hydrogels were mixed with patient synovial fluid (in a 1:1 ratio, v/v), and the ex vivo rheological properties of the mix were characterized.

OA was surgically induced by the transection of the anterior cruciate ligament (ACLT) in female HYLA albino rabbits. One week after surgery, animals were randomly divided into 2 groups. One group (n=9) was injected intra-articularly (right knee) with 600ml saline solution (control) and the other group (n=10) with 600ml of a chitosan hydrogel (VI002, Synolyne Pharma, Belgium). X-rays from the right knee were performed at the time of sacrifice and scored with the Kellgren and Lawrence (K&L) scale. Animals were euthanized 9 weeks after surgery and a macroscopic evaluation of cartilage was done. Histological sections of cartilage areas and of synovial membrane were evaluated according to the OARSI histopathology initiative.

Results:

Chitosan hydrogels were less prone to in vitro oxidative biodegradation than crosslinked and non crosslinked hyaluronan viscosupplements. Their mechanical and lubrication capacity are higher than those of synovial fluid and of hyaluronan viscosupplements. In addition, chitosan hydrogels were easily injected through 25G to 27G needles, with an injection force lower than that of a highly cohesive hyaluronan viscosupplement. Interestingly, when the chitosan hydrogels were mixed with the synovial fluid of OA patients, the mechanical and lubrication capacity were found to be restored.

The X-rays analysis showed a significant decrease (p=0.0079) of the K&L score in rabbits injected with the VI002 chitosan hydrogel (0.40±0.30) compared with control (1.78±0.32). The macroscopic OA cartilage lesions significantly decreased in the lateral compartment in animals treated with VI002 compared to control (21.40±2.67 with VI002 vs. 36.89±3.79 with control; p=0.0041). The synovitis histological scores, mostly synoviocytes hyperplasia and inflammatory infiltrate criteria, were significantly reduced by VI002 (13.25±0.51 with VI002 vs. 14.79±0.35 with control, p=0.0040). Finally, the injection of VI002 hydrogel significantly improved the structure of cartilage (6.54±0.35 with VI002 vs. 8.42±0.38 with control; p =0.0017).

Conclusion:

These results are confirming the high potential of the mono-dose viscosupplementation with non crosslinked chitosan hydrogels specifically designed to protect cartilage and decrease the symptoms associated with OA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/novel-chitosan-hydrogels-for-the-treatment-of-osteoarthritis-mechanical-support-lubrication-and-prevention-of-cartilage-degradation-in-a-rabbit-model-of-osteoarthritis/