Department of Bioengineering, Hanyang University, 222 Wangsimri-ro, Seongdong-gu, Seoul, 04763, Republic of Korea; BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, Hanyang University, 222 Wangsimri-ro, Seongdong-gu, Seoul, 04763, Republic of Korea.
Department of Medical Science, School of Medicine, Konkuk University, Seoul, 143-701, Republic of Korea.
Biomaterials. 2019 Dec;225:119534. doi: 10.1016/j.biomaterials.2019.119534. Epub 2019 Sep 30.
3D culture of stem cells can improve therapeutic effects. However, there is limited research on how to deliver cultured stem cell spheroids to the desired target. Here, we developed lotus seedpod-inspired hydrogel (LoSH) containing microwells for culture and delivery of stem cell spheroids. Human adipose-derived stem cells (hADSCs) inside the square microwells (200 or 400 μm in width with various depths) spontaneously formed spheroids with high viability (94.08 ± 1.56%), and fibronectins conjugated to the hydrogel successfully gripped the spheroids, similar to the funiculus gripping seeds in the lotus seedpod. The spheroids slightly bound to the LoSH surface at 37 °C were detached by the expansion of LoSH at lower temperature of 4 °C. After spheroid formation, LoSH was placed on the target substrate upside-down, expanded at 4 °C for 10 min, and removed from the target. As a result, the spheroids within the microwell were successfully transferred to the target substrate with high transfer efficiency (93.78 ± 2.30%). A delivery of spheroids from LoSH to full-thickness murine skin wound with chimney model showed significant enhancement of the number of SMA-positive vessels at day 21 compared to the group received the same number of spheroids by injection. Together, our findings demonstrate LoSH as a one-step platform that can culture and deliver spheroids to a large target area, which will be useful for various biomedical applications.
3D 培养的干细胞可以提高治疗效果。然而，关于如何将培养的干细胞球状体递送到所需的靶部位的研究还很有限。在这里，我们开发了一种类似于莲蓬的水凝胶（LoSH），其中包含用于培养和输送干细胞球状体的微井。在边长为 200 或 400 μm（宽度不同，深度不同）的方形微井中的人脂肪来源干细胞（hADSCs）会自发形成具有高活力（94.08±1.56%）的球状体，并且与水凝胶共轭的纤维连接蛋白成功地抓住了球状体，类似于莲蓬中种籽的种柄。在 37°C 下，球状体略微与 LoSH 表面结合，在 4°C 下 LoSH 扩展时会脱离。形成球状体后，将 LoSH 倒置放置在靶底物上，在 4°C 下扩展 10 分钟，然后从靶底物上移除。结果，微井中的球状体成功地以高转移效率（93.78±2.30%）转移到靶底物上。从 LoSH 到具有烟囱模型的全层鼠皮伤口的球状体输送显示，与接受相同数量的球状体注射的组相比，第 21 天 SMA 阳性血管的数量明显增加。总之，我们的研究结果表明，LoSH 是一种一步式平台，可用于培养和输送球状体到较大的靶部位，这将对各种生物医学应用非常有用。
