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

The high prevalence and significant impact of osteoporosis make it a leading cause of disability and mortality among older individuals. Neural networks have been reported to have a crucial role in both the physiological and pathological progression of osteoporosis, suggesting neural modulation could be used as an underlying strategy to attenuate the progression of osteoporosis. In this study, we firstly identified the significant relationship between vagus nerve and bone remodeling through artificial intelligence (AI)-based knowledge mining. Subsequently, iron oxide nanoparticles were incorporated into injectable hydrogels (termed M-Gels), which were then 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 min 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.