Division of Oral and Maxillofacial Surgery, Tohoku University Graduate School of Dentistry, Sendai, Japan; Division of Craniofacial Function Engineering, Tohoku University Graduate School of Dentistry, Sendai, Japan.
Division of Craniofacial Function Engineering, Tohoku University Graduate School of Dentistry, Sendai, Japan; Liaison Center for Innovative Dentistry, Tohoku University Graduate School of Dentistry, Sendai, Japan.
Acta Biomater. 2019 Apr 1;88:514-526. doi: 10.1016/j.actbio.2019.02.021. Epub 2019 Feb 15.
Effect of octacalcium phosphate/gelatin composite (OCP/Gel) on angiogenesis was studied by its implantation in rat calvaria critical-sized defect in relation to bone regeneration for 2 and 4 weeks. The implantation of OCP/Gel disks was analyzed by radiomorphometry using a radiopaque material perfusion (Microfil®) method and histomorphometry by hematoxylin and eosin-staining before and after the decalcification. Effect of the OCP dose in the range up to 4 mg per well on the capillary-like tube formation by human umbilical vein endothelial cells (HUVECs) was also examined in a transwell cell culture. The results showed that the blood vessels formation by OCP/Gel group was significantly higher at 2 weeks than other groups but decreased at 4 weeks during the advancement of new bone formation. The capillary-like tube formation was highest in an OCP dose of 1 mg per well while other OCP doses above or below 1 mg did not show such a stimulatory effect. The results established both in vivo and in vitro confirmed that OCP has a positive effect on angiogenesis during bone regeneration in a suitable dose ranges, suggesting that the angiogenesis stimulated by OCP could be involved in the OCP/Gel-enhanced bone regeneration. STATEMENT OF SIGNIFICANCE: We have reported that octacalcium phosphate (OCP) materials display stimulatory capacities on the bone tissue-related cells. However, the effect of OCP on the angiogenesis and its relation to the OCP-enhanced bone regeneration is unknown. This study confirmed the capacity of OCP on angiogenesis before increasing the new bone mass after the implantation of a composite of OCP and gelatin (OCP/Gel). The blood vessels formation took place associated with the area beginning of the new bone formation, which finally decreased together with development of bone formation. Because OCP was ascertained stimulating the capillary-like tube formation in HUVEC culture with a certain OCP dose, the present study is the first report showing the capacity of OCP on angiogenesis during the OCP/Gel-enhanced bone regeneration.
研究了八钙磷/明胶复合材料（OCP/Gel）在大鼠颅骨临界尺寸缺损中的植入对骨再生的血管生成的影响，植入物的研究时间为 2 周和 4 周。使用放射性不透射性材料灌注（Microfil®）方法通过放射形态计量学和脱钙前后的苏木精和伊红染色的组织形态计量学分析 OCP/Gel 圆盘的植入。还在 Transwell 细胞培养中检查了 OCP 剂量在每个孔高达 4mg 范围内对人脐静脉内皮细胞（HUVEC）形成毛细血管样管的影响。结果表明，在新骨形成进展期间，OCP/Gel 组在 2 周时血管生成明显高于其他组，但在 4 周时减少。在每个孔 1mg 的 OCP 剂量下，毛细血管样管形成最高，而其他高于或低于 1mg 的 OCP 剂量则没有显示出这种刺激作用。体内和体外的结果均证实，在适当的剂量范围内，OCP 对骨再生中的血管生成具有积极作用，这表明 OCP 刺激的血管生成可能参与了 OCP/Gel 增强的骨再生。
我们已经报道了八钙磷（OCP）材料对骨组织相关细胞显示出刺激能力。然而，OCP 对血管生成的影响及其与 OCP 增强骨再生的关系尚不清楚。本研究在植入 OCP 和明胶（OCP/Gel）复合材料后增加新骨量之前，证实了 OCP 对血管生成的能力。血管生成发生在新骨形成开始的区域，随着骨形成的发展最终减少。因为已经确定 OCP 以一定的 OCP 剂量刺激 HUVEC 培养中的毛细血管样管形成，所以本研究首次报道了在 OCP/Gel 增强骨再生过程中 OCP 对血管生成的能力。
