Oxygen-Tension Controlled Matrices for Enhanced Osteogenic Cell Survival and Performance
Oxygen-Tension Controlled Matrices for Enhanced Osteogenic Cell Survival and Performance
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DOI：
10.1007/s10439-014-0990-z
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发表时间：
2014-06-01
影响因子：
3.8
通讯作者：
Nukavarapu, S. P.
中科院分区：
文献类型：
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作者：
Amini, A. R.;Nukavarapu, S. P.
临床上可应用的骨组织工程构建体用于大面积骨缺损的成功取决于其允许在整个构建体中均匀骨再生的能力。在整个结构中，血管化不足以及因此导致的氧张力不足已被广泛引用为大面积缺损中成功骨再生所面临的最重要障碍。开发支持骨和血管形成细胞生长和在整个支架结构中发挥功能的构建体是大面积骨缺损修复所需的。在这里，我们开发了氧张力控制的基质，支持整个结构中更均匀的氧水平。具体而言，我们研究了具有优化的孔分布和孔体积百分比的聚乳酸-羟基乙酸共聚物（PLGA）支架，并证明了在体外长期细胞培养后，从结构外部到内部的氧气和pH梯度显著降低。我们通过活/死测定证实了这些优化的构建体支持细胞存活的能力。此外，我们检查了它们支持维持两个临床相关的祖细胞群用于骨组织工程和血管化的能力，即间充质干细胞（MSC）和内皮祖细胞（EPCs），并通过免疫荧光证实了关键骨和血管标志物的表达。
The success of a clinically-applicable bone tissue engineering construct for large area bone defects depends on its ability to allow for homogeneous bone regeneration throughout the construct. Insufficient vascularization, and consequently inadequate oxygen tension, throughout constructs has been largely cited as the most significant obstacle facing successful bone regeneration in large area defects. The development of constructs that support bone and vessel-forming cell growth and function throughout the scaffold structure are desired for large-area bone defect repair. Here, we developed oxygen tension-controlled matrices that support more homogenous oxygen levels throughout the constructs. Specifically, we examined polylactic co-glycolic acid (PLGA) scaffolds with optimized pore distribution and the percent pore volumes, and demonstrated significantly decreased oxygen and pH gradient from the exterior of the construct to the interior after long-term cell culture in vitro. We confirmed the ability of these optimized constructs to support the cellular survival via live/dead assay. In addition, we examined their ability to support the maintenance of two clinically relevant progenitor cell populations for bone tissue engineering and vascularization, namely mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs), and confirmed the expression of key bone and vascular markers via immunofluorescence.