Liu Yufan, Li Jianjun, Yao Bin, Wang Yihui, Wang Rui, Yang Siming, Li Zhao, Zhang Yijie, Huang Sha, Fu Xiaobing
Research Center for Tissue Repair and Regeneration affiliated to the Medical Innovation Research Department, PLA General Hospital and PLA Medical College, 28 Fu Xing Road, Beijing 100853, PR China; PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration, Research Unit of Trauma Care, Tissue Repair and Regeneration, Chinese Academy of Medical Sciences, 2019RU051, 51 Fu Cheng Road, Beijing 100048, PR China.
Research Center for Tissue Repair and Regeneration affiliated to the Medical Innovation Research Department, PLA General Hospital and PLA Medical College, 28 Fu Xing Road, Beijing 100853, PR China; PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration, Research Unit of Trauma Care, Tissue Repair and Regeneration, Chinese Academy of Medical Sciences, 2019RU051, 51 Fu Cheng Road, Beijing 100048, PR China.
Mater Sci Eng C Mater Biol Appl. 2021 Jan;118:111387. doi: 10.1016/j.msec.2020.111387. Epub 2020 Aug 22.
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.
可打印水凝胶的力学特性会影响三维生物打印构建体中的细胞行为，在此背景下，基于水凝胶的生物墨水的硬度可作为调节细胞分化的重要物理信号。在这里，我们使用常用的生物墨水藻酸盐-明胶（Alg-Gel）混合物对间充质干细胞（MSC）进行生物打印，并研究硬度对MSC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Alg-Gel混合物进行生物打印，我们证明硬度差异不会导致细胞铺展、黏附和活力的差异。然而，发现用较硬水凝胶生物打印的MSC会进一步上调汗腺细胞表型、功能和信号通路发育的蛋白质和基因表达。此外，我们发现当用较硬水凝胶生物打印时，MSC中Yes相关蛋白（YAP）在细胞核中的定位增加。这些结果表明，Alg-Gel混合物的硬度是MSC分化的有效调节因子，这可能是通过依赖YAP的机械转导机制实现的。
