Journal
JOURNAL OF BONE AND MINERAL RESEARCH
Volume 27, Issue 5, Pages 1118-1131Publisher
WILEY
DOI: 10.1002/jbmr.1558
Keywords
SIMVASTATIN; GELATIN-HYDROGEL; FRACTURE HEALING; ENDOTHELIAL PROGENITOR CELL; OSTEOGENESIS
Categories
Funding
- Merck Co., Inc.
- Grants-in-Aid for Scientific Research [22112001, 22112002] Funding Source: KAKEN
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Several reports have shown the therapeutic effect of statins on bone formation and neovascularization. However, the effect of the systemic administration of statins is limited due to its metabolism in the liver and clearance in the digestive system. In addition, high-dose administration may cause adverse side effects. To avoid low-efficacy/frequent side effects of high-dose statin treatment, we utilized biodegradable gelatin hydrogel as a drug delivery system of statin for fracture healing. A femoral fracture was created in rats with periosteum cauterization leading to nonunion at 8 weeks postfracture. Rats received local administration of either simvastatin-conjugated gelatin hydrogel (ST-Gel group) or gelatin hydrogel alone (Gel group). Approximately 70% of animals in the ST-Gel group achieved fracture union radiographically and histologically, while only 7% of animals achieved fracture healing in the Gel group. Functional bone healing was also significantly greater with increased angiogenesis- and osteogenesis-related growth factor expressions in periosteal granulation tissue in the ST-Gel group than in the Gel group. Simvastatin locally applied with gelatin hydrogel to fracture sites at a dose similar to that used in clinical settings successfully induced fracture union in a rat unhealing bone fracture model via its effect on both angiogenesis and osteogenesis. (c) 2012 American Society for Bone and Mineral Research.
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