Influence of 3D printed porous architecture on mesenchymal stem cell enrichment and differentiation
Influence of 3D printed porous architecture on mesenchymal stem cell enrichment and differentiation
复制标题
3D打印多孔结构对间充质干细胞富集与分化的影响
DOI：
10.1016/j.actbio.2016.01.007
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发表时间：
2016-03-01
影响因子：
9.7
通讯作者：
Fisher, John P.
中科院分区：
文献类型：
--
作者：
Ferlin, Kimberly M.;Prendergast, Margaret E.;Fisher, John P.
细胞和底层生物材料之间的相互作用对于促进细胞粘附、增殖和功能是重要的。间充质干细胞（MSCs）是一种具有多向分化潜能的成体干细胞，具有巨大的临床应用潜力。MSC的行为和几种材料的性能，包括基板的刚度和孔径之间的关系进行了很好的研究，但很少有研究的多孔结构的影响，在一个三维支架具有良好的控制架构。在这里，我们研究了两种不同的三维打印的孔几何形状对MSC富集和分化的影响。具有有序立方孔几何形状的3D打印支架支持来自未加工骨髓的MSC富集，导致细胞表面标志物表达与组织培养聚苯乙烯的典型粘附相当，这是MSC培养的金标准。结果还显示，与具有有序圆柱形孔的支架相比，具有有序立方孔的支架显著增加经历脂肪形成和软骨形成的MSC的基因表达。然而，在蛋白质表达水平上，这些差异是适度的。对于经历成骨的MSC，基因表达结果表明，圆柱形孔最初可能增加早期成骨标志物表达，而对于具有有序立方孔的支架，在稍后时间点的蛋白质水平表达增加。综上所述，这些结果表明，具有有序立方孔的3D打印支架可能是一个适合的培养系统，用于一步MSC富集和分化。重要性声明间充质干细胞（MSC）具有巨大的治疗潜力，因为它们能够多向分化。MSC的行为，包括谱系定型，可能会受到生物材料特性的影响，包括基质硬度和孔径。通过三维（3D）打印，我们可以在3D培养系统中研究这些关系。在这里，我们制造了两种不同的良好控制的孔几何形状的支架，并研究了对MSC富集和分化的影响。结果表明，具有有序立方孔几何形状的支架支持来自未加工骨髓的MSC富集以及MSC分化，导致脂肪形成和软骨形成期间基因表达增加。这些结果表明，具有有序立方孔的3D打印支架可能是一种适合于单步MSC富集和分化的培养系统。(C)2016 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
The interactions between cells and an underlying biomaterial are important for the promotion of cell adhesion, proliferation, and function. Mesenchymal stem cells (MSCs) have great clinical potential as they are an adult stem cell population capable of multilineage differentiation. The relationship between MSC behavior and several material properties including substrate stiffness and pore size are well investigated, but there has been little research on the influence of porous architecture in a three-dimensional scaffold with a well-controlled architecture. Here, we investigate the impact of two different three-dimensionally printed, pore geometries on the enrichment and differentiation of MSCs. 3D printed scaffolds with ordered cubic pore geometry were supportive of MSC enrichment from unprocessed bone marrow, resulting in cell surface marker expression that was comparable to typical adhesion to tissue culture polystyrene, the gold standard for MSC culture. Results also show that scaffolds fabricated with ordered cubic pores significantly increase the gene expression of MSCs undergoing adipogenesis and chondrogenesis, when compared to scaffolds with ordered cylindrical pores. However, at the protein expression level, these differences were modest. For MSCs undergoing osteogenesis, gene expression results suggest that cylindrical pores may initially increase early osteogenic marker expression, while protein level expression at later timepoints is increased for scaffolds with ordered cubic pores. Taken together, these results suggest that 3D printed scaffolds with ordered cubic pores could be a suitable culture system for single-step MSC enrichment and differentiation.Statement of SignificanceMesenchymal stem cells (MSCs) have great therapeutic potential, as they are capable of multilineage differentiation. MSC behavior, including lineage commitment, may be influenced by biomaterial properties including substrate stiffness and pore size. With three-dimensional (3D) printing, we can investigate these relationships in 3D culture systems. Here, we fabricated scaffolds with two different well controlled pore geometries, and investigated the impact on MSC enrichment and differentiation. Results show that scaffolds with ordered cubic pore geometry were supportive of both MSC enrichment from unprocessed bone marrow as well as MSC differentiation, resulting in increased gene expression during adipogenesis and chondrogenesis. These results suggest that 3D printed scaffolds with ordered cubic pores could be a suitable culture system for single-step MSC enrichment and differentiation. (C) 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.