Department of Bioengineering, Hanyang University, 222 Wangsimri-ro, Seongdong-gu, Seoul 04763, Republic of Korea.
BK21 FOUR, Education and Research Group for Biopharmaceutical Innovation Leader, Hanyang University, 222 Wangsimri-ro, Seongdong-gu, Seoul 04763, Republic of Korea.
Biofabrication. 2021 Apr 2;13(3). doi: 10.1088/1758-5090/abd56c.
Stem cell spheroids have been widely investigated to accelerate bone tissue regeneration. However, the directed differentiation of stem cells into osteoblastic lineage and the prevention of cells from damage by reactive oxygen species (ROS) remain challenge. Here, we developed osteoinductive and ROS scavenging extracellular matrix-mimicking synthetic fibers based on epigallocatechin gallate (EGCG) coating. They were then utilized to fabricate engineered spheroids with human adipose-derived stem cells (hADSCs) for bone tissue regeneration. The EGCG-mineral fibers (EMF) effectively conferred osteoinductive and ROS scavenging signals on the hADSCs within spheroids, demonstrating relative upregulation of antioxidant genes ((25.8 ± 2.1) and(3.3 ± 0.1) and greater level of expression of osteogenic markers,(5.8 ± 0.1) and(5.9 ± 0.1), compared to hADSCs in the spheroids without EMF. Theoverexpression of osteogenic genes from hADSCs was achieved from absence of osteogenic supplements. Furthermore,transplantation of hADSCs spheroids with the EMF significantly promoted calvarial bone regeneration (48.39 ± 9.24%) compared to that from defect only (17.38 ± 6.63%), suggesting that the stem cell spheroid biofabrication system with our novel mineralization method described here is a promising tool for bone tissue regeneration.
干细胞球体已被广泛研究用于加速骨组织再生。然而，将干细胞定向分化为成骨细胞谱系并防止细胞受到活性氧（ROS）的损伤仍然是一个挑战。在这里，我们开发了基于表没食子儿茶素没食子酸酯（EGCG）涂层的具有成骨诱导和 ROS 清除功能的细胞外基质模拟合成纤维。然后，我们利用这些纤维构建了人脂肪来源干细胞（hADSCs）工程化球体，用于骨组织再生。EGCG-矿化纤维（EMF）有效地向球体中的 hADSCs 传递了成骨诱导和 ROS 清除信号，与没有 EMF 的球体中的 hADSCs 相比，抗氧化基因的相对表达水平上调（(25.8 ± 2.1) 和(3.3 ± 0.1)），成骨标志物的表达水平更高（(5.8 ± 0.1) 和(5.9 ± 0.1)）。hADSCs 中成骨基因的过表达是在没有成骨补充剂的情况下实现的。此外，与仅缺陷部位（17.38 ± 6.63%）相比，具有 EMF 的 hADSCs 球体的移植显著促进了颅骨骨再生（48.39 ± 9.24%），这表明我们描述的新型矿化方法的干细胞球体生物制造系统是一种很有前途的骨组织再生工具。
