Ho Christine, Glykofrydis Fokion, Godage Gaveen, Poon Kyle, Kunnan Minnal, Swedlund Benjamin, Murillo Sandra, Morsut Leonardo
Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, California, USA.
bioRxiv. 2025 Jul 9:2025.07.09.663178. doi: 10.1101/2025.07.09.663178.
Robotics draws inspiration from biology, particularly animal locomotion based on muscle-driven contractions. While traditional engineering assembles components sequentially, locomotive animals are built via self-organized developmental programs. Stem cells, under the right conditions, can mimic these processes in vitro, offering a pathway to develop muscle-propelled biobots in a self-organized building process. Here, we demonstrate that existent cardiogenic gastruloid protocols can produce motile aggregates from mouse embryonic stem cells, although with very limited efficiency. We then identify a novel protocol that yields contractile aggregates with higher frequency and larger contractile areas. In this novel protocol, mesendoderm induction using TGF-beta ligands is followed by cardiogenic induction with FGFs and VEGF. Synthetic organizers further control contraction localization. Aggregates developed via this protocol show enhanced motility, marking a step forward towards building motile cardiobots from self-organized biological material. This strategy opens new possibilities for designing autonomous biobots and studying the evolution of muscle-powered movement of multicellular organisms and cardiovascular development.
机器人技术从生物学中汲取灵感，特别是基于肌肉驱动收缩的动物运动。传统工程是按顺序组装部件，而运动动物则是通过自组织发育程序构建的。在合适的条件下，干细胞可以在体外模拟这些过程，为在自组织构建过程中开发肌肉驱动的生物机器人提供了一条途径。在此，我们证明现有的心脏原肠胚样方案可以从小鼠胚胎干细胞产生可运动的聚集体，尽管效率非常有限。然后，我们确定了一种新方案，该方案能以更高的频率和更大的收缩面积产生收缩性聚集体。在这个新方案中，先用转化生长因子-β配体诱导中胚层，然后用成纤维细胞生长因子和血管内皮生长因子进行心脏诱导。合成组织者进一步控制收缩定位。通过该方案培养的聚集体显示出更强的运动能力，这标志着在用自组织生物材料构建可运动心脏机器人方面向前迈进了一步。这种策略为设计自主生物机器人以及研究多细胞生物肌肉驱动运动的进化和心血管发育开辟了新的可能性。
