journal article·2026-08Open access

Magnetoelectric microrobots for spinal cord injury regeneration

Hao Ye, Jingjing Zang, Jiawei Zhu, Denis von Arx, Jian Zhao, Vitaly Pustovalov, Minmin Mao, Qiao Tang, Andrea Veciana, Harun Torlakcik, Elric Zhang, Semih Sevim, Roger Sanchis-Gual, Quan Gao, Xiang-Zhong Chen, Daniel Ahmed, Maria V. Sanchez-Vives, Josep Puigmartí-Luis, Cong Luo, Bradley J. Nelson, Stephan C. F. Neuhauss, Salvador Pané

Nature Materials· Volume 25· Issue 8

Abstract

Spinal cord injury remains difficult to treat because of the intrinsically limited regenerative capacity of neurons. Although neural progenitor cell (NPC) therapies are promising, inadequate graft survival, uncontrolled differentiation and weak functional integration continue to restrict outcomes. Here we report biohybrid microrobots called NPCbots, fabricated by integrating human-induced pluripotent-stem-cell-derived NPCs with magnetoelectric nanoparticles, enabling wireless magnetic navigation and non-invasive neuronal stimulation. A lab-on-a-chip platform allows scalable fabrication and maintains cell viability and differentiation capacity. In a zebrafish spinal cord injury model, alternating magnetic field stimulation of NPCbots induced rapid in vivo neuronal and astrocytic differentiation, enhanced graft integration at the lesion site, and near-complete recovery of swimming and exploratory behaviours within 3 days. In a non-regenerating murine model of complete spinal cord transection, NPCbots were well tolerated for at least 28 days, localized effectively to the injury site, promoted neural differentiation and resulted in substantial improvements in motor function within 4 weeks. These results demonstrate that magnetically guided NPCbots combined with non-invasive magnetoelectric stimulation promote neural repair and functional recovery in preclinical spinal cord injury models.
Source: europepmc · Quality: candidate unverified · Source record ↗

Research context

OpenAlex topics: Micro and Nano Robotics · Planarian Biology and Electrostimulation · Modular Robots and Swarm Intelligence

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

References (50)

Show source-provided references
1. Wang, L. L.-W., Gao, Y., Feng, Z., Mooney, D. J. & Mitragotri, S. Designing drug delivery systems for cell therapy. Nat. Rev. Bioeng. 2, 944–959 (2024).10.1038/s44222-024-00214-0 ↗
2. Chidgey, A. P., Layton, D., Trounson, A. & Boyd, R. L. Tolerance strategies for stem-cell-based therapies. Nature 453, 330–337 (2008).10.1038/nature07041 ↗
3. Lindvall, O. & Kokaia, Z. Stem cells for the treatment of neurological disorders. Nature 441, 1094–1096 (2006).10.1038/nature04960 ↗
4. Nance, E., Pun, S. H., Saigal, R. & Sellers, D. L. Drug delivery to the central nervous system. Nat. Rev. Mater. 7, 314–331 (2022).10.1038/s41578-021-00394-w ↗
5. Vivier, E. et al. Natural killer cell therapies. Nature 626, 727–736 (2024).10.1038/s41586-023-06945-1 ↗
6. Bordignon, C. Stem-cell therapies for blood diseases. Nature 441, 1100–1102 (2006).10.1038/nature04962 ↗
7. Segers, V. F. & Lee, R. T. Stem-cell therapy for cardiac disease. Nature 451, 937–942 (2008).10.1038/nature06800 ↗
8. Baker, D. J., Arany, Z., Baur, J. A., Epstein, J. A. & June, C. H. CAR T therapy beyond cancer: the evolution of a living drug. Nature 619, 707–715 (2023).10.1038/s41586-023-06243-w ↗
9. Adil, M. M. et al. Engineered hydrogels increase the post-transplantation survival of encapsulated hESC-derived midbrain dopaminergic neurons. Biomaterials 136, 1–11 (2017).10.1016/j.biomaterials.2017.05.008 ↗
10. Hallett, P. J. et al. Successful function of autologous iPSC-derived dopamine neurons following transplantation in a non-human primate model of Parkinson’s disease. Cell Stem Cell 16, 269–274 (2015).10.1016/j.stem.2015.01.018 ↗
11. Lindvall, O., Kokaia, Z. & Martinez-Serrano, A. Stem cell therapy for human neurodegenerative disorders-how to make it work. Nat. Med. 10, S42–S50 (2004).10.1038/nm1064 ↗
12. Yasuhara, T. et al. Transplantation of human neural stem cells exerts neuroprotection in a rat model of Parkinson’s disease. J. Neurosci. 26, 12497–12511 (2006).10.1523/JNEUROSCI.3719-06.2006 ↗
13. Cooke, M. J., Vulic, K. & Shoichet, M. S. Design of biomaterials to enhance stem cell survival when transplanted into the damaged central nervous system. Soft Matter 6, 4988–4998 (2010).10.1039/c0sm00448k ↗
14. Gundersen, R. A. et al. Generation of magnetic biohybrid microrobots based on MSC.sTRAIL for targeted stem cell delivery and treatment of cancer. Cancer Nanotechnol. 14, 54 (2023).10.1186/s12645-023-00203-9 ↗
15. Rosenzweig, E. S. et al. Restorative effects of human neural stem cell grafts on the primate spinal cord. Nat. Med. 24, 484–490 (2018).10.1038/nm.4502 ↗
16. Ceto, S., Sekiguchi, K. J., Takashima, Y., Nimmerjahn, A. & Tuszynski, M. H. Neural stem cell grafts form extensive synaptic networks that integrate with host circuits after spinal cord injury. Cell Stem Cell 27, 430–440.e435 (2020).10.1016/j.stem.2020.07.007 ↗
17. Wise, B. L., Seidel, M. F. & Lane, N. E. The evolution of nerve growth factor inhibition in clinical medicine. Nat. Rev. Rheumatol. 17, 34–46 (2021).10.1038/s41584-020-00528-4 ↗
18. Tang, S. et al. The effects of gradients of nerve growth factor immobilized PCLA scaffolds on neurite outgrowth in vitro and peripheral nerve regeneration in rats. Biomaterials 34, 7086–7096 (2013).10.1016/j.biomaterials.2013.05.080 ↗
19. Chen, J. C. et al. A wireless millimetric magnetoelectric implant for the endovascular stimulation of peripheral nerves. Nat. Biomed. Eng. 6, 706–716 (2022).10.1038/s41551-022-00873-7 ↗
20. Chen, J. C. et al. Self-rectifying magnetoelectric metamaterials for remote neural stimulation and motor function restoration. Nat. Mater. 23, 139–146 (2024).10.1038/s41563-023-01680-4 ↗
21. Qu, A. et al. Stimulation of neural stem cell differentiation by circularly polarized light transduced by chiral nanoassemblies. Nat. Biomed. Eng. 5, 103–113 (2021).10.1038/s41551-020-00634-4 ↗
22. Tay, A., Kunze, A., Murray, C. & Di Carlo, D. Induction of calcium influx in cortical neural networks by nanomagnetic forces. ACS Nano 10, 2331–2341 (2016).10.1021/acsnano.5b07118 ↗
23. Marino, A., Arai, S., Hou, E. & Sinibaldi, E. Piezoelectric nanoparticle-assisted wireless neuronal stimulation. ACS Nano 9, 7678–7689 (2015).10.1021/acsnano.5b03162 ↗
24. Chen, R., Canales, A. & Anikeeva, P. Neural recording and modulation technologies. Nat. Rev. Mater. 2, 16093 (2017).10.1038/natrevmats.2016.93 ↗
25. Landers, F. C. et al. On-command disassembly of microrobotic superstructures for transport and delivery of magnetic micromachines. Adv. Mater. 36, e2310084 (2024).10.1002/adma.202310084 ↗
26. Nelson, B. J. An electromagnetic robot for navigating medical devices. Nat. Rev. Bioeng. 2, 370–371 (2024).10.1038/s44222-024-00174-5 ↗
27. Nelson, B. J. & Pane, S. Delivering drugs with microrobots. Science 382, 1120–1122 (2023).10.1126/science.adh3073 ↗
28. Fischer, I., Dulin, J. N. & Lane, M. A. Transplanting neural progenitor cells to restore connectivity after spinal cord injury. Nat. Rev. Neurosci. 21, 366–383 (2020).10.1038/s41583-020-0314-2 ↗
29. Yokota, K. et al. Engrafted neural stem/progenitor cells promote functional recovery through synapse reorganization with spared host neurons after spinal cord injury. Stem Cell Rep. 5, 264–277 (2015).10.1016/j.stemcr.2015.06.004 ↗
30. Courtine, G. & Sofroniew, M. V. Spinal cord repair: advances in biology and technology. Nat. Med. 25, 898–908 (2019).10.1038/s41591-019-0475-6 ↗
31. Erdem, D. et al. Nanoparticle-based magnetoelectric BaTiO3–CoFe2O4 thin film heterostructures for voltage control of magnetism. ACS Nano 10, 9840–9851 (2016).10.1021/acsnano.6b05469 ↗
32. Mushtaq, F. et al. Magnetoelectrically driven catalytic degradation of organics. Adv. Mater. 31, e1901378 (2019).10.1002/adma.201901378 ↗
33. Kim, D. et al. Magnetoelectric effect in hydrogen harvesting: magnetic field as a trigger of catalytic reactions. Adv. Mater. 34, e2110612 (2022).10.1002/adma.202110612 ↗
34. Zhang, E. et al. Magnetic-field-synchronized wireless modulation of neural activity by magnetoelectric nanoparticles. Brain Stimul. 15, 1451–1462 (2022).10.1016/j.brs.2022.10.004 ↗
35. Song, H. et al. Multi-target cell therapy using a magnetoelectric microscale biorobot for targeted delivery and selective differentiation of SH-SY5Y cells via magnetically driven cell stamping. Mater. Horiz. 9, 3031–3038 (2022).10.1039/D2MH00693F ↗
36. Jang, J. & Park, C. B. Magnetoelectric dissociation of Alzheimer’s β-amyloid aggregates. Sci. Adv. 8, eabn1675 (2022).10.1126/sciadv.abn1675 ↗
37. Delaloy, C. et al. MicroRNA-9 coordinates proliferation and migration of human embryonic stem cell-derived neural progenitors. Cell Stem Cell 6, 323–335 (2010).10.1016/j.stem.2010.02.015 ↗
38. Mattila, P. K. & Lappalainen, P. Filopodia: molecular architecture and cellular functions. Nat. Rev. Mol. Cell Biol. 9, 446–454 (2008).10.1038/nrm2406 ↗
39. Kiyota, T., Ingraham, K. L., Jacobsen, M. T., Xiong, H. & Ikezu, T. FGF2 gene transfer restores hippocampal functions in mouse models of Alzheimer’s disease and has therapeutic implications for neurocognitive disorders. Proc. Natl Acad. Sci. USA 108, E1339–E1348 (2011).10.1073/pnas.1102349108 ↗
40. Caldwell, A. L. M. et al. Aberrant astrocyte protein secretion contributes to altered neuronal development in multiple models of neurodevelopmental disorders. Nat. Neurosci. 25, 1163–1178 (2022).10.1038/s41593-022-01150-1 ↗
41. Padmanaban, V. et al. Neuronal substance P drives metastasis through an extracellular RNA-TLR7 axis. Nature 633, 207–215 (2024).10.1038/s41586-024-07767-5 ↗
42. Negrete-Hurtado, A. et al. Autophagy lipidation machinery regulates axonal microtubule dynamics but is dispensable for survival of mammalian neurons. Nat. Commun. 11, 1535 (2020).10.1038/s41467-020-15287-9 ↗
43. Hoop, M. et al. Ultrasound-mediated piezoelectric differentiation of neuron-like PC12 cells on PVDF membranes. Sci. Rep. 7, 4028 (2017).10.1038/s41598-017-03992-3 ↗
44. John, N., Kolb, J. & Wehner, D. Mechanical spinal cord transection in larval zebrafish and subsequent whole-mount histological processing. STAR Protoc. 3, 101093 (2022).10.1016/j.xpro.2021.101093 ↗
45. Anderson, M. A. et al. Astrocyte scar formation aids central nervous system axon regeneration. Nature 532, 195–200 (2016).10.1038/nature17623 ↗
46. Stringer, C., Wang, T., Michaelos, M. & Pachitariu, M. Cellpose: a generalist algorithm for cellular segmentation. Nat. Methods 18, 100–106 (2021).10.1038/s41592-020-01018-x ↗
47. Kemp, P. J. et al. Improving and accelerating the differentiation and functional maturation of human stem cell-derived neurons: role of extracellular calcium and GABA. J. Physiol. 594, 6583–6594 (2016).10.1113/JP270655 ↗
48. Amores, A. et al. Zebrafish hox clusters and vertebrate genome evolution. Science 282, 1711–1714 (1998).10.1126/science.282.5394.1711 ↗
49. Proulx, K., Lu, A. & Sumanas, S. Cranial vasculature in zebrafish forms by angioblast cluster-derived angiogenesis. Dev. Biol. 348, 34–46 (2010).10.1016/j.ydbio.2010.08.036 ↗
50. Bernardos, R. L. & Raymond, P. A. GFAP transgenic zebrafish. Gene Expr. Patterns 6, 1007–1013 (2006).10.1016/j.modgep.2006.04.006 ↗