Research Article: Chitosan-Hyaluronate Hybrid Gel Intraarticular Injection Delays Osteoarthritis Progression and Reduces Pain in a Rat Meniscectomy Model as Compared to Saline and Hyaluronate Treatment

Date Published: May 7, 2012

Publisher: Hindawi Publishing Corporation

Author(s): Shachar Patchornik, Edward Ram, Noah Ben Shalom, Zvi Nevo, Dror Robinson.


Chitosan-Hyaluronate hybrid gel (CHHG) is a self-forming thermo-responsive hydrogel. The current study was undertaken in order to assess the effect of CHHG on rat’s surgically induced osteoarthritis. Methods. Thirteen rats were included in the study. In all rats weight-bearing was assessed using a Linton Incapacitance tester. All rats underwent bilateral medial partial meniscectomy. Four rats received a saline injection in the control knee and a 200-microliter injection of CHHG in the experimental knee. Five rats received a high-molecular weight hyaluronate injection to the control knee and a 200-microliter injection of CHHG in the experimental knee. Four rats underwent the same surgical procedure, allowed to recuperate for seven days and then CHHG and hyaluronate were injected. The animals were followed for 6 weeks. Two weeks after injection of a therapeutic substance the amount of weight-bearing on each knee was evaluated using a Linton Incapacitance meter. Results. Two weeks after induction of osteoarthritis there is less pain in the CHHG-treated knee than in the control-treated knee, as determined using a Lintron Incapacitance meter. After six-weeks the histological appearance of the CHHG-treated knee was superior to that of the controls. This is indicated by thicker cartilage remaining on the medial femoral condyle as well as less cyst formation in the CHHG-treated knee. Discussion. CHHG appears to delay progression of osteoarthritis and lessen pain in a rat surgically-induced knee osteoarthritis model. These results support other published results, indicating that there is an ameliorative effect of chitosan on human and rabbit osteoarthritis.

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Chitin is a nitrogen containing polysaccharide with mechanical strength and stability to chemical degradation. It is formed in the lower phyla of both the animal kingdom (Fauna) as the exoskeleton of invertebra like arthropodes, insects, crabs, lobsters, and mollusks, and in the plant kingdom (Vegetative flora) as well as in fungi. Chitin is probably the most common polymer found in animals, and can be hydrolyzed by a strong alkali to yield chitosan, a substance with quite different properties. Chitosan’s unique features [1, 2] enable its use in various industries and medical applications.

Chitosan is a positively charged polymer and is biocompatible, non-toxic, and nonimmunogenic, allowing its use in the medical, pharmaceutical, cosmetic, and tissue reconstruction fields [19]. It has previously been shown to act as a coagulation agent in penetrating injuries [20]. The use of injectable chitosan has been limited to date due to its potential to cause neutrophil recruitment with inflammation-like effect and indeed prevents surgically induced immunosuppression [21]. Early work on chitosan back to 1999 demonstrated that intra-articular injection led to cartilage overgrowth and arthrofibrosis [22]. This was possible due to macrophage reaction observed when chitosan is degraded.




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