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Improved Survival of Full-Thickness Skin Graft With Low-Molecular Weight Heparin-Protamine Micro/Nanoparticles Including Platelet-Rich Plasma

Takabayashi, Yuki MD*; Ishihara, Masayuki PhD; Kuwabara, Masahiro MD*; Takikawa, Makoto MD, PhD; Nakamura, Shingo PhD; Hattori, Hidemi PhD; Kiyosawa, Tomoharu MD, PhD*

doi: 10.1097/SAP.0000000000001051
Research

Background: Activated platelet-rich plasma secrets many growth factors (GFs), and low-molecular weight heparin-protamine micro/nanoparticles (LMWH-P M/NPs) significantly interact with, enhance, and stabilize the secreted GFs.

Objective: The purpose of this study was to evaluate the effects of LMWH-P M/NPs and GFs (from platelet-rich plasma) on full-thickness skin graft (FTSG).

Methods: A total of 96 inbred male rats were anesthetized and 4-cm2 full-thickness skin wound were created on dorsal skin of rats. LMWH-P M/NPs and GFs, LMWH-P M/NPs, GFs and saline (control) were then injected evenly into cutaneous muscles at the wound. The next day, the rats underwent FTSG. On the indicated days after FTSG, blood flow of FTSG site (wound bed and FTSG) was examined by 2-dimensional laser Doppler blood flowmeter. On 10 days, pictures of FTSG site were taken and FTSG survival rate was evaluated. Histologic analyses of skin samples were performed on 4, 7, and 10 days.

Results: Treatment of full-thickness skin wound with LMWH-P M/NPs and GFs effectively promoted survival rate of FTSG and blood flow of FTSG site compared with those treated with GFs, LMWH-P M/NPs, and control. LMWH-P M/NPs and GFs also promoted new vessel formation at FTSG site.

Conclusions: The prior injection of LMWH-P M/NPs and GFs into wound bed increases FTSG survival rate, and promotes blood flow and angiogenesis at FTSG site.

From the *Department of Plastic and Reconstructive Surgery, National Defense Medical College, Tokorozawa; †Division of Biomedical Engineering, Research Institute, and ‡Department of Medical Engineering, National Defense Medical College, Tokorozawa, Saitama, Japan.

Received July 20, 2016, and accepted for publication, after revision January 3, 2017.

Conflicts of interest: none declared.

This study was partially supported by the Ministry of Education, Culture, Sports, Science and Technology of the Government of Japan (grant 1058500).

Y.T., M.I., and T.K. participated in the conception and design. Y.T., M.I., Y.S., M.K., M.T., S.N., and T.K. participated in analysis and interpretation. Y.T., H.H., M.K., M.T., and S.N. participated in data collection. Y.T., M.I., and T.K. participated in writing the article. Y.T., M.I., H.H., M.K., M.T., S.N., and T.K. participated in the critical revision of the article. Y.T., M.I., and T.K. participated in the final approval of the article. Y.T., H.H., M.K., M.T., and S.N. participated in the statistical analysis. M.I. and T.K. obtained funding. Y.T., M.I., and T.K. participated in the overall responsibility.

Reprints: Masayuki Ishihara, PhD, Division of Biomedical Engineering, Research Institute, National Defense Medical College 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan. E-mail: ishihara@ndmc.ac.jp.

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