Influencing chondrogenic differentiation of human mesenchymal stromal cells in scaffolds displaying a structural gradient in pore size
Influencing chondrogenic differentiation of human mesenchymal stromal cells in scaffolds displaying a structural gradient in pore size
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DOI：
10.1016/j.actbio.2016.03.014
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发表时间：
2016-05-01
影响因子：
9.7
通讯作者：
Moroni, Lorenzo
中科院分区：
文献类型：
--
作者：
Di Luca, Andrea;Szlazak, Karol;Moroni, Lorenzo
关节软骨病变自身愈合能力有限。然而，软骨修复的黄金标准治疗方法，如钻孔、微骨折和镶嵌成形术，会造成进一步的损伤和不稳定的溶液，及时退化成纤维软骨。关节软骨在细胞数量和大小上有一定的梯度，细胞外基质（ECM）组成也有一定的结构梯度。因此，创造具有结构梯度的支架可能是软骨组织再生治疗的一个有吸引力的策略。在本研究中，利用增材制造技术制造了一种具有内置离散孔径梯度的支架。将人间充质基质细胞（hMSCs）植入梯度支架内，对比2个非梯度支架，观察其增殖、分化和ECM沉积情况。在梯度支架和孔径最小的非梯度支架中，糖胺聚糖（GAG）的沉积明显高于孔径最大的非梯度支架。在梯度结构中观察到随着孔径的减小，软骨标志物逐渐增加，同时ECM的形成也越来越紧密。因此，在孔径上显示结构梯度的支架似乎是一种很有前途的策略，可以帮助hMSC软骨分化过程，并可以考虑用于改善软骨组织再生的应用。我们提出了一种新的由增材制造获得的分层支架的发展。结构层次是通过改变表征制备支架的孔网络中的孔径而获得的，并且被证明是支架中影响成体干细胞在软骨谱系中分化的功能元件。具体来说，在孔洞较小的支架区域，干细胞向软骨分化的方向分化。因此，受关节软骨组织的带状组织的启发，孔径梯度可以被认为是设计用于再生医学应用的3D支架的一个新的和重要的元素，特别是对于所有存在梯度物理性质的组织。(C) 2016材料学报Elsevier Ltd.出版。版权所有。
Articular cartilage lesions have a limited ability to heal by themselves. Yet, golden standard treatments for cartilage repair such as drilling, microfracture and mosaicplasty provide further damage and an unstable solution that degenerates into fibrocartilage in time. Articular cartilage presents a number of gradients in cell number and size along with structural gradients in extra cellular matrix (ECM) composition. Therefore, creating scaffolds that display a structural gradient can be an appealing strategy for cartilage tissue regeneration treatments. In the present study, a scaffold with an in-built discrete gradient in pore size was produced by additive manufacturing. Human mesenchymal stromal cells (hMSCs) were seeded within the gradient scaffolds and their proliferation, differentiation and ECM deposition was evaluated with respect to 2 non-gradient scaffolds. Glycosaminoglycan (GAG) deposition was significantly higher in gradient scaffolds and non-gradient scaffolds with the smallest pore size compared to non-gradient scaffolds with the largest pore size. A gradual increase of chondrogenic markers was observed within the gradient structures with decreasing pore size, which was also accompanied by an increasingly compact ECM formation. Therefore, scaffolds displaying a structural gradient in pore size seem to be a promising strategy to aid in the process of hMSC chondrogenic differentiation and could be considered for improved cartilage tissue regeneration applications.Statement of SignificanceWe present the development of a novel hierarchical scaffold obtained by additive manufacturing. Structural hierarchy is obtained by changing pore size within the pore network characterizing the fabricated scaffolds and proves to be a functional element in the scaffold to influence adult stem cell differentiation in the chondrogenic lineage. Specifically, in regions of the scaffolds presenting smaller pores an increasing differentiation of stem cells toward the chondrogenic differentiation is displayed. Taking inspiration from the zonal organization of articular cartilage tissue, pore size gradients could, therefore, be considered as a new and important element in designing 3D scaffolds for regenerative medicine applications, in particular for all those tissues where gradient physical properties are present. (C) 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.