Chitosan-hyaluronate hybrid gel intraarticular injection delays osteoarthritis progression and reduces pain in a rat meniscectomy model as compared to saline and hyaluronate treatment

Abstract

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.

Figure 1

(a) rat knees following medial meniscectomy. Cartilage thickness is higher in the chitosan-hyaluronate-hybrid gel-treated knee than in the hyaluronate-treated knee. (b) environmental scanning electron microscopy seems to indicate that the hybrid gel has an internal structure. The authors hypothesize that the larger hyaluronate molecules (bright lines) appear to chaperon and organize the smaller chitosan molecules. (c) subcutaneous injection in rats does not evoke an inflammatory response macroscopically. The gel forms a discrete nodule (arrow head). This contrasts with the often observed intense inflammatory reaction previously reported with chitosan injection. The difference seems to be related to the method of preparation of the gel and its specific components. Histologically, the gel nodule (red) is surrounded by minimal fibrous capsule without inflammatory cells aggregation (original magnification ×10, Safranin red stain).