Three-dimensional printed PLA scaffold and human gingival stem cell-derived extracellular vesicles: a new tool for bone defect repair.
Three-dimensional printed PLA scaffold and human gingival stem cell-derived extracellular vesicles: a new tool for bone defect repair.
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DOI：
10.1186/s13287-018-0850-0
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发表时间：
2018-04-13
影响因子：
7.5
通讯作者：
Trubiani O
中科院分区：
文献类型：
--
作者：
Diomede F;Gugliandolo A;Cardelli P;Merciaro I;Ettorre V;Traini T;Bedini R;Scionti D;Bramanti A;Nanci A;Caputi S;Fontana A;Mazzon E;Trubiani O
骨组织工程在再生医学领域的作用是近年来的研究热点。近年来，利用人牙龈间充质干细胞（hGMSCs）复合三维（3D）工程支架（PLA）作为促进骨组织再生的一种新的治疗策略受到了广泛关注。这些装置可以通过提供能够支持细胞存活、增殖和分化的3D基底来模拟体内细胞的更有利的内源性微环境。本研究在以下实验组中评价3D PLA、hGMSCs、细胞外囊泡（EV）或聚乙烯亚胺（PEI）工程化EV（PEI-EV）的体外和体内骨缺损再生能力：3D-PLA、3D-PLA + hGMSCs、3D-PLA + EV、3D-PLA + EVs + hGMSCs、3D-PLA + PEI-EV、3D-PLA + PEI-EVs + hGMSCs。使用扫描电子显微镜和非破坏性显微计算机断层扫描的支架的结构参数进行了评价。纳米形貌的表面特征进行了研究，通过原子力显微镜。支架在112天的评价中显示出统计学显著的质量损失沿着。我们的体外结果显示3D-PLA + EV + hGMSCs和3D-PLA + PEI-EV + hGMSCs均未显示细胞毒性。然而，3D-PLA + PEI-EV + hGMSC表现出更大的成骨诱导性，如通过下一代测序（NGS）进行的形态学评价和转录组学分析所揭示的。此外，体内结果显示，植入到受到颅骨皮质骨组织损伤的大鼠中的3D-PLA + PEI-EV + hGMSC和3D-PLA + PEI-EV支架能够通过显示更好的成骨特性来改善骨愈合。这些结果也得到了计算机断层扫描评价的支持，该评价显示了颅骨损伤的修复。重建骨损伤的完整性可能是治疗意外或手术创伤，特别是颅骨创伤的一种有前途的策略。本文的在线版本（10.1186/s13287-018-0850-0）包含补充材料，可供授权用户使用。
The role of bone tissue engineering in the field of regenerative medicine has been a main research topic over the past few years. There has been much interest in the use of three-dimensional (3D) engineered scaffolds (PLA) complexed with human gingival mesenchymal stem cells (hGMSCs) as a new therapeutic strategy to improve bone tissue regeneration. These devices can mimic a more favorable endogenous microenvironment for cells in vivo by providing 3D substrates which are able to support cell survival, proliferation and differentiation. The present study evaluated the in vitro and in vivo capability of bone defect regeneration of 3D PLA, hGMSCs, extracellular vesicles (EVs), or polyethyleneimine (PEI)-engineered EVs (PEI-EVs) in the following experimental groups: 3D-PLA, 3D-PLA + hGMSCs, 3D-PLA + EVs, 3D-PLA + EVs + hGMSCs, 3D-PLA + PEI-EVs, 3D-PLA + PEI-EVs + hGMSCs. The structural parameters of the scaffold were evaluated using both scanning electron microscopy and nondestructive microcomputed tomography. Nanotopographic surface features were investigated by means of atomic force microscopy. Scaffolds showed a statistically significant mass loss along the 112-day evaluation. Our in vitro results revealed that both 3D-PLA + EVs + hGMSCs and 3D-PLA + PEI-EVs + hGMSCs showed no cytotoxicity. However, 3D-PLA + PEI-EVs + hGMSCs exhibited greater osteogenic inductivity as revealed by morphological evaluation and transcriptomic analysis performed by next-generation sequencing (NGS). In addition, in vivo results showed that 3D-PLA + PEI-EVs + hGMSCs and 3D-PLA + PEI-EVs scaffolds implanted in rats subjected to cortical calvaria bone tissue damage were able to improve bone healing by showing better osteogenic properties. These results were supported also by computed tomography evaluation that revealed the repair of bone calvaria damage. The re-establishing of the integrity of the bone lesions could be a promising strategy in the treatment of accidental or surgery trauma, especially for cranial bones. The online version of this article (10.1186/s13287-018-0850-0) contains supplementary material, which is available to authorized users.
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影响因子：
14
作者：
Ishaug-Riley, SL;Crane-Kruger, GM;Mikos, AG
通讯作者：
Mikos, AG
影响因子：
3.1
作者：
Diomede, F.;Zini, N.;Trubiani, O.
通讯作者：
Trubiani, O.
影响因子：
6.1
作者：
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影响因子：
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作者：
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通讯作者：
Hallett, MB
影响因子：
5.8
作者：
Aravindan, Latha;Bicknell, Katrina A.;Williams, Adrian C.
通讯作者：
Williams, Adrian C.