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由带血管化β-磷酸三钙支架和间充质干细胞构建的组织工程骨的成骨和成血管作用。

Osteogenesis and angiogenesis of tissue-engineered bone constructed by prevascularized β-tricalcium phosphate scaffold and mesenchymal stem cells.

机构信息

Institute of Orthopaedics and Traumatology, The Third Affiliated Hospital, Guangzhou Medical University, People's Republic of China.

出版信息

Biomaterials. 2010 Dec;31(36):9452-61. doi: 10.1016/j.biomaterials.2010.08.036. Epub 2010 Sep 24.

DOI:10.1016/j.biomaterials.2010.08.036
PMID:20869769
Abstract

Although vascularized tissue-engineered bone grafts (TEBG) have been generated ectopically in several studies, the use of prevascularized TEBG for segmental bone defect repair are rarely reported. In current study, we investigated the efficacy of prevascularized TEBG for segmental defect repair. The segmental defects of 15 mm in length were created in the femurs of rabbits bilaterally. In treatment group, the osteotomy site of femur was implanted with prevascularized TEBG, which is generated by seeding mesenchymal stem cells (MSCs) into β-TCP scaffold, and prevascularization with the insertion of femoral vascular bundle into the side groove of scaffold; whereas in the control group, only MSC mediated scaffolds (TEBG) were implanted. The new bone formation and vascularization were investigated and furthermore, the expression of endogenous vascular endothelial growth factor (VEGF) which might express during defect healing was evaluated, as well. At 4, 8, and 12 weeks postoperatively, the treatment of prevascularized TEBG led to significantly higher volume of regenerated bone and larger amount of capillary infiltration compared to non-vascularized TEBG. The expression of VEGF in mRNA and protein levels increased with implantation time and peaked at 4 weeks postoperatively, followed by a slow decrease, however, treatment group expressed a significant higher level of VEGF than control group throughout the whole study. In conclusion, this study demonstrated that prevascularized TEBG by insertion of vascular bundle could significantly promote the new bone regeneration and vascularization compared to non-vascularized TEBG, which could be partially explained by the up-regulated expression of VEGF.

摘要

尽管在几项研究中已经在外周异位生成了血管化组织工程骨移植物(TEBG),但很少有报道使用预血管化 TEBG 进行节段性骨缺损修复。在本研究中,我们研究了预血管化 TEBG 修复节段性骨缺损的效果。在双侧兔股骨中创建了 15mm 长度的节段性缺损。在治疗组中,将预先血管化的 TEBG 植入股骨的截骨部位,该 TEBG 通过将间充质干细胞(MSCs)接种到β-TCP 支架中并将股血管束插入支架侧槽中进行预血管化;而在对照组中,仅植入 MSC 介导的支架(TEBG)。研究了新骨形成和血管化情况,此外还评估了在缺损愈合过程中可能表达的内源性血管内皮生长因子(VEGF)的表达。术后 4、8 和 12 周时,与非血管化 TEBG 相比,预血管化 TEBG 的治疗导致再生骨体积明显增加,毛细血管渗透量也更大。VEGF 的表达在 mRNA 和蛋白水平上随植入时间的增加而增加,并在术后 4 周达到峰值,随后缓慢下降,但整个研究过程中治疗组的 VEGF 表达水平均显著高于对照组。总之,本研究表明,通过插入血管束的预血管化 TEBG 可显著促进新骨再生和血管化,这可以部分解释为 VEGF 的上调表达。

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