Multi-level magnetic microrobot delivery strategy within a hierarchical vascularized organ-on-a-chip

Abstract

Targeted microrobotic delivery within the circulatory system holds significant potential for medical theranostic applications. Existing delivery strategies of microrobots encounter challenges such as slow speed, limited navigation control, and dispersal under dynamic flow conditions. Furthermore, within the realm of microrobots, in vitro testing platforms often lack essential biological microenvironments, while in vivo studies conducted on animal models are constrained by limited detection resolution. In this study, we propose a multi-level magnetic delivery strategy that integrates a tethered microrobotic guidewire and untethered swimming microrobots. The amalgamation compensates for their inherent constraints, ensuring a robust and highly efficient delivery of microrobots under complex physiological conditions over extensive distances. Concurrently, a hierarchical vascular network encompassing engineered arteries/veins and capillary networks was constructed by integrating vasculogenesis and endothelial cell (EC) lining strategies, thereby providing an in vivo-like testing platform for microrobots. Experimental evidence demonstrates that the flexible microrobotic guidewire can be precisely directed to any entrance of the second-tier branches, with its inner lumen providing an “express lane” for rapid passage of microrobots through complex fluidic environments without direct contact. After release, dynamically assembled swarms could effectively locomote on the micro-topography of the EC-lined channel surface without becoming trapped and congregate within specified regions inside capillary lumens when guided collectively by a biologically safe magnetic field. Additionally, the superparamagnetic capabilities of microrobotic swarms ensure their dissolution into monodispersed entities upon withdrawal of the magnetic field, mitigating the risk of intravascular thrombosis. The hierarchical vascularized organ-on-a-chip platform establishes a comprehensive testing platform that integrates imaging, control, and a functional 3D microvascular environment, thereby enhancing its suitability for microrobotic applications encompassing targeted drug delivery, thrombus ablation, sensing and diagnosis, etc.