An in vivo comparative study of the gelatin microtissue-based bottom-up strategy and top-down strategy in bone tissue engineering application

An in vivo comparative study of the gelatin microtissue-based bottom-up strategy and top-down strategy in bone tissue engineering application
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基于明胶微组织的自下而上策略和自上而下策略在骨组织工程应用中的体内比较研究。

DOI:
10.1002/jbm.a.36587
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发表时间:
2019-03-01
影响因子:
4.9
通讯作者:
Wang, Zhenxing
Wang, Zhenxing
中科院分区:
工程技术3区
文献类型:
--
作者:
Luo, Chao;Fang, Huimin;Wang, Zhenxing

文献摘要

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组织工程化骨移植是治疗骨缺损的一种有效方法。然而,目前的构建策略(自上而下[TD]策略)的缺点,如营养物质的有限传输和接种细胞的不均匀分布,导致对大段骨缺损的治疗效果不令人满意。理论上,基于组织工程微组织(TEMT)的自底向上(BU)策略在保存种子细胞和血管化方面是有效的,因此被认为是TEBG的更好的替代方案。然而,很少有研究集中在比较由TD或BU策略制备的TEBG的体内性能。在这里,我们开发了一个异位骨形成大鼠模型,以比较这两种构建策略在体内的性能。将由明胶TEMT(BU策略)和大块组织(BT; TD策略)制成的TEBG接种相同数量的大鼠骨髓来源的间充质干细胞,并在5 mm聚二甲基硅氧烷室中制造。将移植物植入同一大鼠的皮下袋中。植入后4周,显微计算机断层扫描和苏木精-伊红染色结果表明,微组织(MT)组形成的骨组织多于BT组。CD 31染色进一步证实MT组中有更多的血管,表明BU策略在诱导血管生成方面具有上级优势。该对比研究为BU构建策略的体内应用和骨组织工程治疗骨缺损提供了证据。© 2018 Wiley Periodicals,Inc. J Biomed Mater Res Part A:107A:678-688,2019.
Tissue-engineered bone grafts (TEBGs) represent a promising treatment for bone defects. Nevertheless, drawbacks of the current construction strategy (top-down [TD] strategy) such as limited transmission of nutrients and nonuniform distribution of seeded cells, result in an unsatisfied therapeutic effect on large segmental bone defects. Theoretically, tissue-engineered microtissue (TEMT)-based bottom-up (BU) strategy is effective in preserving seed cells and vascularization, thus being regarded as a better alternative for TEBGs. Yet, there are few studies focusing on the comparison of the in vivo performance of TEBGs fabricated by TD or BU strategy. Here, we developed an ectopic bone formation rat model to compare the performance of these two construction strategies in vivo. TEBGs made from gelatin TEMT (BU strategy) and bulk tissue (BT; TD strategy) were seeded with equal number of rat bone marrow-derived mesenchymal stem cells and fabricated in 5 mm polydimethylsiloxane chambers. The grafts were implanted into subcutaneous pockets in the same rat. Four weeks after implantation, microcomputed tomography and hematoxylin and eosin staining results demonstrated that more bony tissue was formed in the microtissue (MT) group than in the BT group. CD31 staining further confirmed that there were more blood vessels in the MT group, indicating that the BU strategy was superior in inducing angiogenesis. This comparative study provides evidence that the BU construction strategy is more effective for in vivo application and bone defect treatment by bone tissue engineering. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 678-688, 2019.