Kim Eun Mi, Lee Gyeong Min, Lee Sangmin, Kim Se-Jeong, Lee Dongtak, Yoon Dae Sung, Joo Jinmyoung, Kong Hyunjoon, Park Hee Ho, Shin Heungsoo
Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea.
Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea; BK21 FOUR Education and Research Group for Biopharmaceutical Innovation Leader, Department of Bioengineering, College of Engineering, Hanyang University, Republic of Korea.
Int J Biol Macromol. 2022 Jan 1;194:903-913. doi: 10.1016/j.ijbiomac.2021.11.145. Epub 2021 Nov 25.
Cell spheroids are three-dimensional cell aggregates that have been widely employed in tissue engineering. Spheroid encapsulation has been explored as a method to enhance cell-cell interactions. However, the effect of hydrogel mechanical properties on spheroids, specifically soft hydrogels (<1 kPa), has not yet been studied. In this study, we determined the effect of encapsulation of stem cell spheroids by hydrogels crosslinked with different concentrations of gelatin methacryloyl (GelMA) on the functions of the stem cells. To this end, human adipose-derived stem cell (ADSC) spheroids with a defined size were prepared, and spheroid-laden hydrogels with various concentrations (5, 10, 15%) were fabricated. The apoptotic index of cells from spheroids encapsulated in the 15% hydrogel was high. The migration distance was five-fold higher in cells encapsulated in the 5% hydrogel than the 10% hydrogel. After 14 days of culture, cells from spheroids in the 5% hydrogel were observed to have spread and proliferated. Osteogenic factor and pro-angiogenic factor production in the 15% hydrogel was high. Collectively, our results indicate that the functionality of spheroids can be regulated by the mechanical properties of hydrogel, even under 1 kPa. These results indicate that spheroid-laden hydrogels are suitable for use in 3D tissue construction.
细胞球体是三维细胞聚集体，已在组织工程中得到广泛应用。球体包封已被探索为一种增强细胞间相互作用的方法。然而，水凝胶力学性能对球体，特别是软水凝胶（<1千帕）的影响尚未得到研究。在本研究中，我们确定了用不同浓度甲基丙烯酰化明胶（GelMA）交联的水凝胶包封干细胞球体对干细胞功能的影响。为此，制备了具有确定大小的人脂肪来源干细胞（ADSC）球体，并制备了含有不同浓度（5%、10%、15%）球体的水凝胶。包封在15%水凝胶中的球体的细胞凋亡指数较高。包封在5%水凝胶中的细胞的迁移距离比包封在10%水凝胶中的细胞高五倍。培养14天后，观察到5%水凝胶中球体的细胞已经铺展并增殖。15%水凝胶中促骨生成因子和促血管生成因子的产生较高。总体而言，我们的结果表明，即使在1千帕以下，水凝胶的力学性能也可以调节球体的功能。这些结果表明，载有球体的水凝胶适用于三维组织构建。
