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Superparamagnetic iron oxide (SPIO) nanoparticles play an important role in mediating precise and effective magnetic neuro-stimulation and can help overcome limitations related to penetration depth and spatial resolution. However, nanoparticles readily diffuse in vivo, decreasing the spatial resolution and activation efficiency. In this study, we employed a microfluidic means to fabricate injectable microhydrogels encapsulated with SPIO nanoparticles, which significantly improved the stability of nanoparticles, increased the magnetic properties, and reinforced the stimulation effectivity. The fabricated magnetic microhydrogels were highly uniform in size and sphericity, enabling minimally invasive injection into brain tissue. The long-term residency in the cortex up to 22 weeks and the safety of brain tissue were shown using a mouse model. In addition, we quantitatively determined the magneto-mechanical force yielded by only one magnetic microhydrogel using a video-based method. The force was found to be within 7–8 pN under 10 Hz magnetic stimulation by both theoretical simulation and experimental measurement. Lastly, electrophysiological measurement of brain slices showed that the magnetic microhydrogels offer significant advantages in terms of neural activation relative to dissociative SPIO nanoparticles. A universal strategy is thus offered for performing magnetic neuro-stimulation with an improved prospect for biomedical translation.


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Magneto-mechanical effect of magnetic microhydrogel for improvement of magnetic neuro-stimulation

Show Author's information Le Xue1Qing Ye1Linyuan Wu1Dong Li2Siyuan Bao1Qingbo Lu3Sha Liu1Dongke Sun2Zonghai Sheng4Zhijun Zhang3,5( )Ning Gu6( )Jianfei Sun1( )
State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory of Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210009, China
School of Mechanic Engineering, Southeast University, Nanjing 211189, China
Department of Neurology, Affiliated Zhongda Hospital, School of Medicine, Institution of Neuropsychiatry, Southeast University, Nanjing 210009, China
Paul C. Lauterbur Research Center for Biomedical Imaging, Key Laboratory for Magnetic Resonance and Multimodality Imaging of Guangdong Province, Shenzhen Key Laboratory of Ultrasound Imaging and Therapy, CAS Key Laboratory of Health Informatics, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
Department of Mental Health and Public Health, Faculty of Life and Health Sciences, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
School of Medicine, Nanjing University, Nanjing 210008, China

Abstract

Superparamagnetic iron oxide (SPIO) nanoparticles play an important role in mediating precise and effective magnetic neuro-stimulation and can help overcome limitations related to penetration depth and spatial resolution. However, nanoparticles readily diffuse in vivo, decreasing the spatial resolution and activation efficiency. In this study, we employed a microfluidic means to fabricate injectable microhydrogels encapsulated with SPIO nanoparticles, which significantly improved the stability of nanoparticles, increased the magnetic properties, and reinforced the stimulation effectivity. The fabricated magnetic microhydrogels were highly uniform in size and sphericity, enabling minimally invasive injection into brain tissue. The long-term residency in the cortex up to 22 weeks and the safety of brain tissue were shown using a mouse model. In addition, we quantitatively determined the magneto-mechanical force yielded by only one magnetic microhydrogel using a video-based method. The force was found to be within 7–8 pN under 10 Hz magnetic stimulation by both theoretical simulation and experimental measurement. Lastly, electrophysiological measurement of brain slices showed that the magnetic microhydrogels offer significant advantages in terms of neural activation relative to dissociative SPIO nanoparticles. A universal strategy is thus offered for performing magnetic neuro-stimulation with an improved prospect for biomedical translation.

Keywords: magnetic stimulation, magnetic microhydrogel, long-term residency, magneto-mechanical effect, superparamagnetic iron oxide (SPIO) nanoparticles

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Publication history
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Acknowledgements

Publication history

Received: 26 October 2022
Revised: 23 December 2022
Accepted: 01 January 2023
Published: 19 February 2023
Issue date: May 2023

Copyright

© Tsinghua University Press 2023

Acknowledgements

Acknowledgements

This study was partly supported by the National Key Research and Development Program of China (No. 2021YFA1201403 to J. F. S.), China Science and Technology Innovation 2030-Major Project (Nos. 2022ZD0211701 to Z. J. Z. and 2022ZD0211704 to J. F. S.), the National Natural Science Key Foundation of China (Nos. 81830040 and 82130042 to Z. J. Z.), the Science and Technology Program of Guangdong (No. 2018B030334001 to Z. J. Z.), and the Postgraduate Research & Practice Innovation Program of Jiangsu Province (No. SJCX21_0146 to L. X.). The authors would like to thank Dr. Huan Wang from Sun Yat-Sen University and Prof. Yuanjin Zhao from Nanjing Drum Tower Hospital for assistance with the fabrication of microhydrogels.

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