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Sustained bFGF-Release Tubes for Peripheral Nerve Regeneration: Comparison with Autograft

Takagi, Takehiko M.D., Ph.D.; Kimura, Yu Ph.D.; Shibata, Shinsuke M.D., Ph.D.; Saito, Harukazu M.D., Ph.D.; Ishii, Ken M.D., Ph.D.; Okano, Hirotaka J. M.D., Ph.D.; Toyama, Yoshiaki M.D., Ph.D.; Okano, Hideyuki M.D., Ph.D.; Tabata, Yasuhiko Ph.D., D.Med.Sci., D.Pharm.; Nakamura, Masaya M.D., Ph.D.

Plastic and Reconstructive Surgery: October 2012 - Volume 130 - Issue 4 - p 866–876
doi: 10.1097/PRS.0b013e318262f36e
Hand/Peripheral Nerve: Original Articles

Background: Despite numerous articles on the use of artificial nerve conduits, autologous nerve transplants remain the most effective for nerve repair. To improve this technique, the authors examined conduits containing gelatin hydrogel as a carrier enabling the sustained release of basic fibroblast growth factor (bFGF).

Methods: To confirm sustained bFGF release in vivo, nerve-guide tubes containing iodine-125–labeled bFGF with or without gelatin hydrogel were implanted under the skin of mice, and the remaining radioactivity was measured. Next, a 15-mm segment of the sciatic nerve was resected and repaired with autologous nerve (group 1), a tube with gelatin hydrogel and bFGF (group 2), a tube with bFGF alone (group 3), or a tube only (group 4). Histologic and functional analyses were performed for 16 weeks after surgery.

Results: The radioactivity from iodine-125–labeled bFGF incorporated into gelatin hydrogel decreased more slowly than iodine-125–labeled bFGF alone. Four weeks after surgery, significantly more regenerating axons were detected in group 2 than in groups 3 and 4, but the axonal density in group 2 was lower than in group 1. Similarly, the animals in group 2 showed significantly better motor performance than those in groups 3 and 4, but worse than those in group 1. The animals in groups 1 and 2 showed significantly better sensory recovery than those in groups 3 and 4.

Conclusions: The nerve-guide tube containing gelatin hydrogel and bFGF promoted axonal regeneration after peripheral nerve injury, but not as well as autologous transplants. Understanding the limitations of this technique will facilitate its improvement for clinical applications.

Tokyo and Kyoto, Japan

From the Departments of Orthopedic Surgery and Physiology, Keio University School of Medicine; the Advanced Biomedical Engineering Research Unit and the Institute for Frontier Medical Sciences, Kyoto University; and the Department of Orthopedic Surgery, Murayama Medical Center, National Hospital Organization.

Received for publication April 5, 2012; accepted April 9, 2012.

Disclosure:None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this article.

Masaya Nakamura, M.D., Ph.D., Department of Orthopedic Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan,

©2012American Society of Plastic Surgeons