Department of Biomechatronic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University (SKKU), Suwon 16419, South Korea.
Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, South Korea.
Theranostics. 2021 Jan 16;11(7):3331-3347. doi: 10.7150/thno.53928. eCollection 2021.
A spheroid is an aggregation of single cells with structural and functional characteristics similar to those of 3D native tissues, and it has been utilized as one of the typical three-dimensional (3D) cell models. Scaffold-free spheroids provide outstanding reflection of tissue complexity in a 3D -like environment, but they can neither fabricate realistic macroscale 3D complex structures without avoiding necrosis nor receive direct external stimuli (i.e., stimuli from mechanical or topographical cues). Here, we propose a spheroid-laden electrospinning process to obtain model achieved using the synergistic effect of the unique bioactive components provided by the spheroids and stimulating effects provided by the aligned nanofibers. To show the functional activity of the spheroid-laden structures, we used myoblast-spheroids to obtain skeletal muscle, comprising highly aligned myotubes, utilizing an uniaxially arranged topographical cue. The spheroid-electrospinning was used to align spheroids directly by embedding them in aligned alginate nanofibers, which were controlled with various materials and processing parameters. The spheroids laden in the alginate nanofibers showed high cell viability (>90%) and was compared with that of a cell-laden alginate nanofiber that was electrospun with single cells. Consequently, the spheroids laden in the aligned nanofibers showed a significantly higher degree of myotube formation and maturation. Results suggested that the model using electrospun spheroids could potentially be employed to understand myogenic responses for various drug tests.
球体是具有类似于 3D 天然组织的结构和功能特征的单细胞聚集体，它已被用作典型的 3D 细胞模型之一。无支架球体在类似于 3D 的环境中提供了对组织复杂性的出色反映，但它们既不能制造没有避免坏死的逼真的宏观 3D 复杂结构，也不能接收直接的外部刺激（即，来自机械或形貌线索的刺激）。在这里，我们提出了一种球体负载的静电纺丝工艺，以获得通过球体提供的独特生物活性成分的协同作用和取向纳米纤维提供的刺激作用来实现的模型。为了显示球体负载结构的功能活性，我们使用成肌细胞球体获得了骨骼肌，包含高度取向的肌管，利用单轴排列的形貌线索。通过将球体嵌入到受控的各种材料和处理参数的取向藻酸钠纳米纤维中，直接对球体进行静电纺丝排列。负载在藻酸钠纳米纤维中的球体表现出高细胞活力（>90％），并与用单细胞静电纺丝的负载藻酸钠纳米纤维中的细胞活力进行了比较。结果表明，使用静电纺丝球体的 模型可以潜在地用于理解各种 药物测试中的成肌反应。
