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微尺度与纳米尺度支架结构对间充质干细胞软骨分化的影响。

Microscale versus nanoscale scaffold architecture for mesenchymal stem cell chondrogenesis.

机构信息

Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA.

出版信息

Tissue Eng Part A. 2011 Mar;17(5-6):831-40. doi: 10.1089/ten.TEA.2010.0409. Epub 2010 Dec 14.

DOI:10.1089/ten.TEA.2010.0409
PMID:20973751
Abstract

Nanofiber scaffolds, produced by the electrospinning technique, have gained widespread attention in tissue engineering due to their morphological similarities to the native extracellular matrix. For cartilage repair, studies have examined their feasibility; however these studies have been limited, excluding the influence of other scaffold design features. This study evaluated the effect of scaffold design, specifically examining a range of nano to micron-sized fibers and resulting pore size and mechanical properties, on human mesenchymal stem cells (MSCs) derived from the adult bone marrow during chondrogenesis. MSC differentiation was examined on these scaffolds with an emphasis on temporal gene expression of chondrogenic markers and the pluripotent gene, Sox2, which has yet to be explored for MSCs during chondrogenesis and in combination with tissue engineering scaffolds. Chondrogenic markers of aggrecan, chondroadherin, sox9, and collagen type II were highest for cells on micron-sized fibers (5 and 9 μm) with pore sizes of 27 and 29 μm, respectively, in comparison to cells on nano-sized fibers (300 nm and 600 to 1400 nm) having pore sizes of 2 and 3 μm, respectively. Undifferentiated MSCs expressed high levels of the Sox2 gene but displayed negligible levels on all scaffolds with or without the presence of inductive factors, suggesting that the physical features of the scaffold play an important role in differentiation. Micron-sized fibers with large pore structures and mechanical properties comparable to the cartilage ECM enhanced chondrogenesis, demonstrating architectural features as well as mechanical properties of electrospun fibrous scaffolds enhance differentiation.

摘要

纳米纤维支架通过静电纺丝技术制备,由于其形态与天然细胞外基质相似,在组织工程中得到了广泛关注。对于软骨修复,已有研究探讨了其可行性;然而,这些研究受到限制,未考虑到支架设计特征的其他影响。本研究评估了支架设计的影响,具体研究了纳米到微米大小的纤维以及由此产生的孔径和机械性能对骨髓间充质干细胞(MSCs)向软骨分化的影响。在这些支架上检测了 MSC 的分化,特别强调了软骨形成标志物和多能基因 Sox2 的时间基因表达,Sox2 在软骨形成过程中以及与组织工程支架结合使用时,尚未在 MSCs 中进行研究。与孔径分别为 2 和 3μm 的纳米纤维(300nm 和 600-1400nm)相比,在孔径分别为 27μm 和 29μm 的微米纤维(5μm 和 9μm)上,细胞的软骨聚集蛋白、软骨粘连蛋白、Sox9 和 II 型胶原等软骨形成标志物的表达最高。与未分化的 MSC 相比,在所有支架上(无论是否存在诱导因子),Sox2 基因的表达水平都很高,但表达水平都很低,这表明支架的物理特征在分化中起着重要作用。具有大孔结构和类似于软骨细胞外基质的机械性能的微米纤维增强了软骨形成,表明静电纺丝纤维支架的结构特征和机械性能增强了分化。

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