Biodegradable Gelatin Hydrogels Incorporating Fibroblast Growth Factor 2 Promote Healing of Horizontal Tears in Rabbit Meniscus

Abstract

The purpose of this study was to investigate the in vivo effects of gelatin hydrogels (GHs) incorporating fibroblast growth factor 2 (FGF-2) on meniscus repair in a rabbit model. FGF-2 was biologically stabilized by incorporation into GHs. This system enables FGF-2 to be released with its biologic activity intact. A total of 64 skeletally mature female Japanese white rabbits were used. A horizontal tear was made in the medial meniscus, and these tears were divided into 4 groups: GH-FGF, GH-no FGF, FGF (FGF-2 alone), and no treatment. The meniscus was evaluated histologically at 2, 4, 8, and 12 weeks after surgery. Cell density and the percentages of proliferating cell nuclear antigen-positive cells and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells were measured, and a scoring system ranging from 5 points (complete healing) to 0 points (no evidence of healing) was used. Cell density was significantly higher in the GH-FGF group than in the other 3 groups at 2, 4, 8, and 12 weeks (P < .01). The percentage of proliferating cell nuclear antigen-positive cells was significantly higher whereas the percentage of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells was significantly lower in the GH-FGF group at 2 and 4 weeks after surgery (P < .05). At 4, 8, and 12 weeks after surgery, healing scores were significantly higher in the GH-FGF group (2.5 points, 2.7 points, and 3.0 points, respectively) than in the GH-no FGF group (1.3 points, 1.4 points, and 2.0 points, respectively) (P < .05). GHs incorporating FGF-2 significantly stimulated proliferation and inhibited the death of meniscal cells until 4 weeks, thereby increasing meniscal cell density and enhancing meniscal repair in a rabbit model. GHs incorporating FGF-2 are able to enhance the healing of meniscal injury.