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

Narita, Atsushi; Takahara, Masatoshi; Sato, Daisuke; Ogino, Toshihiko; Fukushima, Shigenobu; Kimura, Yu; Tabata, Yasuhiko

doi:10.1016/j.arthro.2011.08.294

« Previous Next »Arthroscopy: The Journal of Arthroscopic and Related Surgery
Volume 28, Issue 2 , Pages 255-263, February 2012

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

Atsushi Narita, M.D., Ph.D.
- Department of Orthopaedic Surgery, Yamagata University School of Medicine, Yamagata, Japan
- Address correspondence to Atsushi Narita, M.D., Ph.D., Department of Orthopaedic Surgery, Yamagata University School of Medicine, Iida-Nishi-2-2-2, Yamagata 990-9585, Japan
Masatoshi Takahara, M.D., Ph.D.
- Department of Orthopaedic Surgery, Yamagata University School of Medicine, Yamagata, Japan
Daisuke Sato, M.D.
- Department of Orthopaedic Surgery, Yamagata University School of Medicine, Yamagata, Japan
Toshihiko Ogino, M.D., Ph.D.
- Department of Orthopaedic Surgery, Yamagata University School of Medicine, Yamagata, Japan
Shigenobu Fukushima, M.D.
- Department of Orthopaedic Surgery, Saiseikai Yamagata Hospital, Yamagata, Japan
Yu Kimura, M.Eng.
- Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
Yasuhiko Tabata, Ph.D., D.M.Sc., D.Pharm.
- Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan

Received 24 March 2011; accepted 11 August 2011. published online 28 November 2011.

Purpose

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.

Methods

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.

Results

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).

Conclusions

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.