Reduction of intraarticular adhesion of knee by local application of rapamycin in rabbits via inhibition of fibroblast proliferation and collagen synthesis

Abstract

Background: The formation of intraarticular adhesion is a common complication after total knee arthroplasty or anterior cruciate ligament reconstruction. Previously, little research was reported regarding whether the local application of rapamycin (RAPA) could reduce intraarticular adhesion following knee surgery. In our present study, we determined the therapeutic effect of RAPA by local application on the reduction of intraarticular adhesion following knee surgery in rabbits.

Methods: In this study, we built the model of knee surgery according to a previous study. The decorticated areas of the cortical bone were exposed and covered with cotton pads soaked with different concentrations of RAPA or physiological saline for 10 min. All of the rabbits were euthanized 4 weeks after the surgery. Macroscopic evaluation of the hydroxyproline content, the histological morphological analysis and collagen density and fibroblast density were used to evaluate the effect of RAPA on reducing intraarticular adhesion.

Results: The results shown that RAPA could significantly inhibit the proliferation of fibroblasts and reduce collagen synthesis; in the rabbit model of knee surgery, there were weak scar tissues around the decorticated areas in the 0.2 mg/ml RAPA group; moderate scar tissues were found in the 0.1 mg/ml RAPA group. However, severe fibrous adhesions were found in the 0.05 mg/ml RAPA group and the control group. The hydroxyproline content and the fibroblast density in the 0.2 mg/ml and 0.1 mg/ml RAPA groups were significantly less than those of the control group.

Conclusions: We concluded that the local application of RAPA could reduce intraarticular adhesion after knee surgery in the rabbit model; this effect was mediated by inhibition of fibroblast proliferation and collagen synthesis, which may provide a new method for reducing intraarticular adhesion after clinical knee surgery.

Keywords: Collagen synthesis; Fibroblast; Intraarticular adhesion; Rapamycin.

Fig. 1

Hydroxyproline content in intraarticular scar tissue in the RAPA-treated groups and the control group. The hydroxyproline content is expressed as micrograms per milligram (μg/mg). *P < 0.05, compared with control group; #P < 0.05, and the 0.2 mg/ml RAPA group compared with the other RAPA groups

Fig. 2

The histological view of the intraarticular adhesion issues in the decorticated areas treated with RAPA (0.2 mg/ml (a), 0.1 mg/ml (b) and 0.05 mg/ml (c)) and saline (d). Note that loose scar tissues were found in the decorticated areas treated with the 0.1 mg/ml group and 0.2 mg/ml RAPA group. Dense scar tissue was found in the decorticated areas treated with saline. The sections were stained with HE (×200)

Fig. 3

The collagen density of intraarticular adhesion tissue in the RAPA groups (0.2mg/ml (a), 0.1mg/ml (b), 0.05mg/ml (c) and the control group (d). The collagen tissues show blue in the section with Masson’s trichrome staining under the light microscope (×200). RAPA could reduce collagen synthesis and fibrosis. The density of collagen tissue in the 0.2 mg/ml RAPA group and the 0.1 mg/ml RAPA group revealed a significant decrease compared with those in the 0.05 mg/ml RAPA group and control group

Fig. 4

The collagen optical density in each group. *P < 0.05, compared with the control group; #P < 0.05, and the 0.2 mg/ml RAPA group compared with the other RAPA groups

Fig. 5

Fibroblast counts of scar adhesion tissues from each group. *P < 0.05, compared with the control group; #P < 0.05, the 0.2 mg/ml RAPA group compared with the other RAPA-treated groups