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Effects of CB-VEGF-A Injection in Rat Flap Models for Improved Survival

Akimoto, Minekatsu M.D., Ph.D.; Takeda, Akira M.D., Ph.D.; Matsushita, Osamu M.D., Ph.D.; Inoue, Joe Ph.D.; Sakamoto, Keiko; Hattori, Masakazu Ph.D., D.V.M.; Kounoike, Natsuko M.D.; Uchinuma, Eiju M.D., Ph.D.

Plastic and Reconstructive Surgery: April 2013 - Volume 131 - Issue 4 - p 717–725
doi: 10.1097/PRS.0b013e3182818b34
Experimental: Original Articles

Background: Various carriers have been tested as drug delivery systems in an attempt to sustain the action of growth factors. Gene therapy has also been adopted to achieve lasting effects but without satisfactory results. Because the authors believe that the angiogenic effect of vascular endothelial growth factor (VEGF) can be enhanced by anchoring the fusion protein composed of the Clostridium-derived collagen-binding domain and recombinant VEGF-A164 (CB-VEGF-A) in the tissue, they examined the changes in blood flow of random pattern flaps following treatment of the dorsal region of the rat with the fusion proteins before skin flap elevation.

Methods: The authors administered CB-VEGF-A subcutaneously into the dorsal region of Sprague-Dawley rats 7 days before creation of skin flaps, and compared the necrosis rate observed on the seventh day after flap elevation with that of vehicle controls. The authors also performed comparison with a group treated by subcutaneous administration of non–collagen-binding domain–binding VEGF. The skin flaps were also examined histologically.

Results: The flap necrosis rate was lower in the CB-VEGF-A group (36.7 ± 7.4 percent) than in the control group (48.2 ± 5.4 percent). However, no improvement was observed in the non–collagen-binding domain–binding VEGF group. Moreover, histologic examination revealed an increase in the subcutaneous blood vessel counts.

Conclusion: CB-VEGF-A has an angiogenic effect on rat dorsal skin flaps and improves flap survival.

Kanagawa, Okayama, and Kyoto, Japan

From the Department of Plastic and Aesthetic Surgery, Kitasato University School of Medicine; the Department of Bacteriology, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine; and the Department of Immunology and Cell Biology and the Center for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto University.

Received for publication June 26, 2012; accepted October 17, 2012.

Disclosure: The authors have no financial interest in any of the products or devices mentioned in this article.

Minekatsu Akimoto, M.D., Ph.D.; Department of Plastic and Aesthetic Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa 252-0344, Japan,

©2013American Society of Plastic Surgeons