The stiffness of hydrogel-based bioink impacts mesenchymal stem cells differentiation toward sweat glands in 3D-bioprinted matrix
The stiffness of hydrogel-based bioink impacts mesenchymal stem cells differentiation toward sweat glands in 3D-bioprinted matrix
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DOI：
10.1016/j.msec.2020.111387
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发表时间：
2021-01-01
影响因子：
7.9
通讯作者：
Fu, Xiaobing
中科院分区：
文献类型：
--
作者：
Liu, Yufan;Li, Jianjun;Fu, Xiaobing
可打印水凝胶的力学方面可以影响3d生物打印结构中的细胞行为，在这种情况下，基于水凝胶的生物链接的刚度可以作为调节细胞分化的重要物理线索。本研究采用海藻酸盐-明胶（algo -gel）混合物生物打印间充质干细胞（MSCs），研究硬度对间充质干细胞向汗腺分化的影响。通过压缩测试评估力学性能，发现较高的压缩模量与较高的Alg-Gel浓度相关。使用这些海藻-凝胶混合物进行生物打印，我们证明了硬度变化不会导致细胞扩散、粘附和活力的差异。然而，更硬的水凝胶打印的MSCs进一步上调了汗腺细胞表型、功能和信号通路发育的蛋白和基因表达。此外，我们发现当用更硬的水凝胶进行生物打印时，骨髓间充质干细胞中细胞核中yes相关蛋白（YAP）的定位增加。这些结果表明，Alg-Gel混合物的硬度是MSC分化的有效调节剂，这可能是通过yap依赖的机械转导机制实现的。
Mechanical aspects of printable hydrogels can impact cell behavior in 3D-bioprinted constructs, and in this context the stiffness of hydrogel-based bioink can serve as an important physical cue in regulating cell differentiation. Here we bioprinted mesenchymal stem cells (MSCs) by the commonly used bioink alginate-gelatin (Alg-Gel) blends and investigated the influence of stiffness on MSC differentiation toward sweat glands. Mechanical properties were assessed through compression testing and it was found that higher compressive modulus was associated with the higher Alg-Gel concentrations. Using these Alg-Gel blends for bioprinting, we demonstrated that stiffness variance cannot cause differences in cell spreading, adhesion and viability. However, MSCs bioprinted by stiffer hydrogels were found to further upregulate the protein and gene expression of sweat gland cell phenotype, function and development of signaling pathways. Furthermore, we found that the increased Yes-associated protein (YAP) localization of nuclei in MSCs when bioprinted by stiffer hydrogels. These results illustrated that the stiffness of Alg-Gel blends is a potent regulator of MSC differentiation, which was possibly achieved through a YAP-dependent mechanotransduction mechanism.