Lotus seedpod-inspired hydrogels as an all-in-one platform for culture and delivery of stem cell spheroids

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 mu m 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 degrees C were detached by the expansion of LoSH at lower temperature of 4 degrees C. After spheroid formation, LoSH was placed on the target substrate upside-down, expanded at 4 degrees 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.