Topical cutaneous application of CO2 accelerates bone healing in a rat femoral defect model

BMC Musculoskeletal Disorders

Sang Yang Lee¹  Takehiko Matsushita²  Tomoaki Fukui²  Yohei Kumabe²  Ryosuke Kuroda²  Keisuke Oe²  Takahiro Niikura²  Takahiro Oda²  Yu Kuroiwa²  Michio Arakura²  Tomoyuki Matsumoto²  Toshihiro Akisue³  Yoshitada Sakai⁴  Shunsuke Takahara⁵ 

[1] 0000 0000 8864 3422, grid.410714.7, Department of Orthopaedic Surgery, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, 142-8666, Tokyo, Japan;0000 0001 1092 3077, grid.31432.37, Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, 650-0017, Kobe, Japan;0000 0001 1092 3077, grid.31432.37, Department of Rehabilitation Science, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-ku, 654-0142, Kobe, Japan;0000 0001 1092 3077, grid.31432.37, Division of Rehabilitation Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, 650-0017, Kobe, Japan;Department of Orthopaedic Surgery, Hyogo Prefectural Kakogawa Medical Center, 203 Kanno, Kanno-cho, 675-8555, Kakogawa, Japan;

关键词: CO;    Bone healing;    Bone defect;   

DOI  :  10.1186/s12891-019-2601-5

来源: publisher

【 摘 要 】

BackgroundBone defects may occur because of severe trauma, nonunion, infection, or tumor resection. However, treatments for bone defects are often difficult and have not been fully established yet. We previously designed an efficient system of topical cutaneous application of carbon dioxide (CO2) using a novel hydrogel, which facilitates CO2 absorption through the skin into the deep area within a limb. In this study, the effect of topical cutaneous application of CO2 on bone healing was investigated using a rat femoral defect model.MethodsIn this basic research study, an in vivo bone defect model, fixed with an external fixator, was created using a rat femur. The affected limb was shaved, and CO2 was applied for 20 min/day, 5 days/week. In the control animals, CO2 gas was replaced with air. Radiographic, histological, biomechanical, and genetic assessments were performed to evaluate bone healing.ResultsRadiographically, bone healing rate was significantly higher in the CO2 group than in the control group at 4 weeks (18.2% vs. 72.7%). The degree of bone healing scored using the histopathological Allen grading system was significantly higher in the CO2 group than in the control group at 2 weeks (1.389 ± 0.334 vs. 1.944 ± 0.375). The ultimate stress, extrinsic stiffness, and failure energy were significantly greater in the CO2 group than in the control group at 4 weeks (3.2 ± 0.8% vs. 38.1 ± 4.8%, 0.6 ± 0.3% vs. 41.5 ± 12.2%, 2.6 ± 0.8% vs. 24.7 ± 5.9%, respectively.). The volumetric bone mineral density of the callus in micro-computed tomography analysis was significantly higher in the CO2 group than in the control group at 4 weeks (180.9 ± 43.0 mg/cm3 vs. 247.9 ± 49.9 mg/cm3). Gene expression of vascular endothelial growth factor in the CO2 group was significantly greater than that in the control group at 3 weeks (0.617 ± 0.240 vs. 2.213 ± 0.387).ConclusionsTopical cutaneous application of CO2 accelerated bone healing in a rat femoral defect model. CO2 application can be a novel and useful therapy for accelerating bone healing in bone defects; further research on its efficacy in humans is warranted.

【 授权许可】

CC BY