Aoki Shimpo, Fujii Mao, Fujie Toshinori, Nishiwaki Keisuke, Miyazaki Hiromi, Saitoh Daizoh, Takeoka Shinji, Kiyosawa Tomoharu, Kinoshita Manabu
Department of Plastic Surgery, National Defense Medical College, Saitama, Japan.
Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.
Wound Repair Regen. 2017 Nov;25(6):1008-1016. doi: 10.1111/wrr.12604. Epub 2018 Feb 9.
Although human recombinant basic fibroblast growth factor (bFGF) is widely used for wound healing, daily treatment with bFGF is required because of its short half-life. An effective controlled-release system of bFGF is, therefore, desired in clinical settings. To investigate the efficacy of a bFGF-loaded nanosheet for wound healing, focusing on the controlled-release of bFGF, bFGF-loaded poly(lactic-co-glycolic acid) (PGLA) nanosheets were developed, and their in vitro release profile of bFGF and their in vivo efficacy for wound healing were examined. A polyion complex of positively charged human recombinant bFGF and negatively charged alginate was sandwiched between PLGA nanosheets (70 nm thick for each layer). The resulting bFGF-loaded nanosheet robustly adhered to silicon skin by observation using a microscratch test. bFGF was gradually and continuously released over three days in an in vitro incubation study. Treatment with the bFGF-loaded nanosheets (every 3 day for 15 days) as well as with a conventional bFGF spray effectively promoted wound healing of mouse dorsal skin defects with accelerated tissue granulation and angiogenesis, although the dose of bFGF used in the treatment with the bFGF nanosheets was approximately 1/20 of the sprayed bFGF. In conclusion, we developed a bFGF-loaded nanosheet that sustained a continuous release of bFGF over three days and effectively promoted wound healing in mice.
尽管人重组碱性成纤维细胞生长因子（bFGF）被广泛用于伤口愈合，但由于其半衰期短，需要每日进行bFGF治疗。因此，临床上需要一种有效的bFGF控释系统。为了研究负载bFGF的纳米片对伤口愈合的疗效，重点关注bFGF的控释，我们制备了负载bFGF的聚乳酸-乙醇酸共聚物（PGLA）纳米片，并检测了其bFGF的体外释放曲线及其对伤口愈合的体内疗效。带正电荷的人重组bFGF与带负电荷的海藻酸盐的聚离子复合物夹在PLGA纳米片之间（每层厚70nm）。通过微划痕试验观察，所得负载bFGF的纳米片牢固地粘附在硅皮肤上。在体外孵育研究中，bFGF在三天内逐渐持续释放。用负载bFGF的纳米片治疗（每3天一次，共15天）以及用传统的bFGF喷雾剂治疗均有效地促进了小鼠背部皮肤缺损的伤口愈合，加速了组织肉芽形成和血管生成，尽管在负载bFGF纳米片治疗中使用的bFGF剂量约为喷雾bFGF的1/20。总之，我们开发了一种负载bFGF的纳米片，其能在三天内持续释放bFGF，并有效地促进了小鼠的伤口愈合。
