4D anisotropic skeletal muscle tissue constructs fabricated by staircase effect strategy
4D anisotropic skeletal muscle tissue constructs fabricated by staircase effect strategy
复制标题
DOI：
10.1088/1758-5090/ab1d07
复制
发表时间：
2019-07-01
期刊：
影响因子：
9
通讯作者：
Zhang, Lijie Grace
中科院分区：
文献类型：
--
作者：
Miao, Shida;Nowicki, Margaret;Zhang, Lijie Grace
与天然组织纤维排列形态（如骨骼肌）一样，在各向异性组织工程中，单向各向异性支架作为一种指导细胞行为的手段是非常需要的。相比之下，等高线状楼梯表现出定向地形线索，被认为是熔融沉积建模（FDM）不可避免的缺陷。在这项研究中，我们将通过FDM和表面涂层技术（FCT）的结合，将这种阶梯缺陷转化为一种有效的生物工程策略，研究地形线索对调节人间充质干细胞（hMSCs）向骨骼肌组织的行为的影响。这种综合方法可以使用不同的生物材料来制造形状特定的、多维的、各向异性的支架。二维各向异性支架，首次展示了不同的聚己内酯浓度，有效地指导hMSC排列，特别是当支架固定在支撑环上时。通过在fdm打印的牺牲结构内表面涂覆聚合物溶液，开发出具有薄壁特征的3D各向异性支架，并通过自建的旋转生物反应器调节种子间质干细胞。使用逐层涂层，与形状记忆聚合物一起，准备了展示形状固定和恢复过程的智能结构，将这项研究带入了4D打印领域。免疫荧光染色和实时定量聚合酶链反应分析证实，通过FCT产生的地形线索显著增强了肌生成基因的表达，包括成肌细胞分化蛋白-1、desmin和肌球蛋白重链-2。我们认为，由于包括骨骼肌在内的许多组织和器官具有高度组织化和各向异性的细胞外基质成分，因此FCT策略在组织工程中具有广泛的应用潜力。
Like the morphology of native tissue fiber arrangement (such as skeletal muscle), unidirectional anisotropic scaffolds are highly desired as a means to guide cell behavior in anisotropic tissue engineering. In contrast, contour-like staircases exhibit directional topographical cues and are judged as an inevitable defect of fused deposition modeling (FDM). In this study, we will translate this staircase defect into an effective bioengineering strategy by integrating FDM with surface coating technique (FCT) to investigate the effect of topographical cues on regulating behaviors of human mesenchymal stem cells (hMSCs) toward skeletal muscle tissues. This integrated approach serves to fabricate shape-specific, multiple dimensional, anisotropic scaffolds using different biomaterials. 2D anisotropic scaffolds, first demonstrated with different polycaprolactone concentrations herein, efficiently direct hMSC alignment, especially when the scaffold is immobilized on a support ring. By surface coating the polymer solution inside FDM-printed sacrificial structures, 3D anisotropic scaffolds with thin wall features are developed and used to regulate seeded hMSCs through a self-established rotating bioreactor. Using layer-by-layer coating, along with a shape memory polymer, smart constructs exhibiting shape fix and recovery processes are prepared, bringing this study into the realm of 4D printing. Immunofluorescence staining and real-time quantitative polymerase chain reaction analysis confirm that the topographical cues created via FCT significantly enhance the expression of myogenic genes, including myoblast differentiation protein-1, desmin, and myosin heavy chain-2. We conclude that there are broad application potentials for this FCT strategy in tissue engineering as many tissues and organs, including skeletal muscle, possess highly organized and anisotropic extracellular matrix components.