A Neurospheroid‐Based Microrobot for Targeted Neural Connections in a Hippocampal Slice

Abstract

Functional restoration by the re‐establishment of cellular or neural connections remains a major challenge in targeted cell therapy and regenerative medicine. Recent advances in magnetically powered microrobots have shown potential for use in controlled and targeted cell therapy. In this study, a magnetic neurospheroid (Mag‐Neurobot) that can form both structural and functional connections with an organotypic hippocampal slice (OHS) is assessed using an ex vivo model as a bridge toward in vivo application. The Mag‐Neurobot consists of hippocampal neurons and superparamagnetic nanoparticles (SPIONs); it is precisely and skillfully manipulated by an external magnetic field. Furthermore, the results of patch‐clamp recordings of hippocampal neurons indicate that neither the neuronal excitabilities nor the synaptic functions of SPION‐loaded cells are significantly affected. Analysis of neural activity propagation using high‐density multi‐electrode arrays shows that the delivered Mag‐Neurobot is functionally connected with the OHS. The applications of this study include functional verification for targeted cell delivery through the characterization of novel synaptic connections and the functionalities of transported and transplanted cells. The success of the Mag‐Neurobot opens up new avenues of research and application; it offers a test platform for functional neural connections and neural regenerative processes through cell transplantation.

Magnetically Actuated Microscaffold with Controllable Magnetization and Morphology for Regeneration of Osteochondral Tissue

“…Recently, scaffolds that are capable of cell loading and with a micrometer size and wireless actuation have been developed to overcome the limitations of cell-mediated therapies [ 10 , 11 , 12 ]. Spheroid microrobots have also been developed, which are made by co-culturing cells and magnetic nanoparticles (MNPs) [ 13 , 14 ]. Among these, wirelessly actuated microscaffolds can be loaded with stem cells and have demonstrated differentiation into chondrocytes [ 10 ].…”

Dual‐Responsive Nanorobot‐Based Marsupial Robotic System for Intracranial Cross‐Scale Targeting Drug Delivery

“…[1] Currently, MNRs DOI: 10.1002/adma.202306876 powered by various mechanisms, such as chemical, [2][3][4][5] light, [6][7][8][9] magnetic, [10][11][12][13] ultrasound, [14][15][16] and more advanced hybrid mechanisms, [17][18][19][20][21][22] have been extensively studied and display diverse types of motion. In this regard, MNRs outperform traditional passive nanocarriers in terms of targeting capability, [23][24][25] drug delivery efficiency, [26][27][28] and tissue penetration [29][30][31] based on their active movement. Although targeting movement of MNRs to several organs and large cavities (e.g., brain, [3,17,32] gastrointestinal tract, [33][34][35] and bladder [36,37] ) has been achieved, considering the velocity limited by their tiny bodies, human-scale navigation of MNRs will inevitably result in a compromise of the delivery efficiency.…”