Knowledge mining inspired therapy of osteoporosis by magnetic hydrogel mediated precise stimulation of vagus nerve under a rotational magnetic field

Significant relationship between vagus nerve and bone remodeling was identified through artificial intelligence (AI)-based knowledge mining. Iron oxide nanoparticles incorporated injectable hydrogels (termed M-Gels) were directly injected to envelop a single vagus nerve in the left neck of rats to prolong the retention issue in peripheral tissues (up to 20 weeks). Magnetic vagus nerve stimulation (mVNS) showed a rapid response characteristic of vagus activation. Notably, the mVNS administered at 20 Hz twice daily for 15 minutes over 16 weeks effectively improved bone metabolism in vivo. Using AI, we discovered that gut microbiota is an underlying cause of this phenomenon. This innovative mVNS method demonstrated the correlation between the vagus nerve and bone remodeling, revealing promising potential for osteoporosis therapy by long term mVNS.

A team of material scientists led by Jian-fei Sun from Southeast University in Nanjing, China recently outlined the magnetic vagus nerve stimulation (mVNS) for treatment of osteoporosis. The neural network plays a crucial role in the physiological and pathological signal interaction and regulation of degenerative orthopedic diseases, and is key to processes such as bone joint development, metabolism, remodeling, and repair. mVNS offers a novel method and strategy for the precise treatment of degenerative orthopedic diseases

The team published their article in Nano Research on May 29, 2025.

“In this study, we first identified the significant relationship between vagus nerve and bone remodeling through artificial intelligence (AI)-based knowledge mining. Magnetic vagus nerve stimulation (mVNS) effectively improved bone metabolism in vivo via varying gut microbiota.” said Jian-Fei Sun, author of the paper, professor in the State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices and School of Biological Science and Medical Engineering at Southeast University.

Magnetic stimulation is recognized as a highly promising neuromodulation approach with potential therapeutic applications for both peripheral and central nervous system disorders. However, current magnetic stimulation technologies primarily employ broad-range magnetic fields applied to target areas, which suffer from several limitations including poor spatial precision, inadequate penetration depth, difficult localization, and lack of specificity. Furthermore, the magnetic field must reach a certain intensity threshold to be effective, yet achieving both sufficient penetration depth and spatial precision simultaneously remains challenging. These limitations are difficult to overcome solely through optimization of coil physical parameters. Consequently, magnetic hydrogel mediated magnetic stimulation lies in breaking through the spatial resolution and depth limitations to achieve precise magnetic modulation of neural circuits.

Under mild pulsed magnetic fields, the non-focused magnetic field mediated by magnetic nanomaterials enables selective and precise magnetic modulation. By investigating the retention patterns of injectable magnetic hydrogels around target nerves, this study elucidates the mechanism of their mediated precise neural stimulation in neural activation, thereby providing a novel therapeutic strategy for targeted osteoporosis treatment.

The research team outlines the AI-based knowledge mining may be used to seek new target for the treatment of osteoporosis. “We focused on both neural- and osteoporosis-related components using knowledge-mining techniques to identify potential targets for the treatment of osteoporosis. Statistical analysis revealed that vagus nerve could be considered a promising target for magnetic stimulation-based therapy in osteoporosis treatment” Jian-Fei Sun said.

Other contributors include Peng Wang, Senlin Chai, Yibo Zhang, Zhihong Xu and Qing Jiang from the Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School at Nanjing University; Xucai Wang and Wenhui Pei from the Co‑Innovation Center for Efficient Processing and Utilization of Forest Resources, College of Chemical Engineering at Nanjing Forestry University; Liming Zheng from the Department of Orthopedic Surgery, the Second Affiliated Hospital at Zhejiang University School of Medicine; and Ning Gu from the Medical School at Nanjing University

This work was supported by the National Basic Research Program of China (2021YFA1201403), the National Natural Science Foundation of China (32271413).

About the Authors

Dr. Jianfei Sun Jianfei Sun is a Professor and Principal Investigator in the College of Bioscience and Medical Engineering at Southeast University (Nanjing). He earned his Bachelor’s degree (2000) and Doctor of Engineering (2008) from Southeast University (Nanjing), where he has since dedicated his career to teaching and research. Currently, he directs the Jiangsu Key Laboratory of Biomaterials and Devices and holds leadership roles in multiple academic and industry committees, including: Standing Committee Member, Magnetic Resonance Imaging Equipment and Technology Committee (China Medical Equipment Association); Deputy Head, Stem Cell Industry Transformation Group (Neural Regeneration and Repair Committee, Chinese Research Hospital Association); Member, Basic and Translational Neuroregulation Branch (Chinese Neuroscience Society); Member, Bioelectromagnetics Branch (Chinese Society for Biomedical Engineering). His research focuses on medical magnetic nanomaterials and electromagnetic therapies. Professor Sun has published over 90 papers in high-impact journals (Angewandte Chemie, Advanced Materials, IEEE Transactions on Biomedical Engineering, Biomaterials), secured nine invention patents, and facilitated technology transfer valued at 3 million RMB. He has also led a government-funded industrialization project (30 million RMB), incubated a tech startup, and attracted over 10 million RMB in social capital investment.

About Nano Research

Nano Research is a peer-reviewed, open access, international and interdisciplinary research journal, sponsored by Tsinghua University and the Chinese Chemical Society, published by Tsinghua University Press on the platform SciOpen. It publishes original high-quality research and significant review articles on all aspects of nanoscience and nanotechnology, ranging from basic aspects of the science of nanoscale materials to practical applications of such materials. After 18 years of development, it has become one of the most influential academic journals in the nano field. Nano Research has published more than 1,000 papers every year from 2022, with its cumulative count surpassing 7,000 articles. In 2024 InCites Journal Citation Reports, its 2024 IF is 9.0 (8.7, 5 years), and it continues to be the Q1 area among the four subject classifications. Nano Research Award, established by Nano Research together with TUP and Springer Nature in 2013, and Nano Research Young Innovators (NR45) Awards, established by Nano Research in 2018, have become international academic awards with global influence.