Hybrid living biobots consisting of active cells hold promise for significant applications as, for example, intelligent devices in medical engineering and organisms with specific functions in synthetic biology. However, the design and creation of living biobots with various cells remain a challenge. In this paper, we propose a three-dimensional inverse optimization strategy based on the pixel topology optimization method, to design self-propelled living biobots with the function of biomechanical actuations. For illustration, we design several biobots composed of active and passive elements that mimic cardiomyocytes and passive epidermal cells sourced from such as , human induced pluripotent stem cells or neonatal rats Their topologies are optimized by implementing the active constitutive relations of cells into the multicellular topological interpolation model. Effects of nutrient concentrations, elasticity, and anisotropic contraction of cardiomyocytes on the topologies and functionalities of the biobots are examined. In addition, we unveil the living topological interfaces generated by the collective actuations of the optimized biobots. We show a potential of collective biobots for high-throughput drug screening owing to their distinct biomechanical responses under healthy and sick conditions. The proposed inverse optimization method can be extended to design various functional multicellular biological systems, which impacts the studies of organ development, synthetic biology, and medical engineering.

中文翻译：

---

具有目标函数的三维多细胞生物机器人逆向设计

由活性细胞组成的混合生物机器人有望实现重大应用，例如医学工程中的智能设备和合成生物学中具有特定功能的生物体。然而，设计和制造具有各种细胞的活体生物机器人仍然是一个挑战。在本文中，我们提出了一种基于像素拓扑优化方法的三维逆优化策略，以设计具有生物力学驱动功能的自驱动生物机器人。为了说明这一点，我们设计了几个由主动和被动元件组成的生物机器人，这些元件模仿来自人类诱导多能干细胞或新生大鼠的心肌细胞和被动表皮细胞。通过将细胞的主动本构关系实施到多细胞拓扑插值中，优化了它们的拓扑模型。研究了心肌细胞的营养浓度、弹性和各向异性收缩对生物机器人的拓扑和功能的影响。此外，我们还揭示了由优化的生物机器人的集体驱动生成的活体拓扑界面。我们展示了集体生物机器人在高通量药物筛选方面的潜力，因为它们在健康和患病条件下具有独特的生物力学反应。所提出的逆优化方法可以扩展到设计各种功能性多细胞生物系统，这影响了器官发育、合成生物学和医学工程的研究。