Injectable Magneto-Thermoresponsive Hydrogel For Spatiotemporally Controlled Periodontal Regeneration

This study aimed to engineer a dual-responsive injectable hydrogel integrating SPIONs and static magnetic fields (SMFs) for spatiotemporal control of dental follicle stem cell (DFSC)-mediated periodontal regeneration. An injectable small intestine submucosa/Pluronic F127 hydrogel co-loaded with SPIONs and DFSCs was developed. Material properties were characterized via SEM/TEM (nanostructure), rheometry, and magnetometry. In vitro, biocompatibility and migration were assessed using CCK-8, live/dead staining, and Transwell assays. Osteogenic differentiation was evaluated by ALP/ARS staining, qPCR, and Western blot. In vivo, a rat periodontal defect model received hydrogel-SMF treatment, with regeneration analyzed through Micro-CT, histopathology (H&E/Masson), immunofluorescence, and SPION retention tracked via Prussian blue/MRI. The hydrogel exhibited temperature/pH-dependent sol-gel transition and magnetic-responsive nanostructures, with SMF enhancing DFSC migration and osteogenic differentiation. Hydrogel-SMF synergistically promoted alveolar bone regeneration and oriented periodontal ligament realignment, while maintaining controlled SPION retention and systemic biosafety. Mechanistic studies revealed SMF-activated mechanotransduction pathways and anti-inflammatory cytokine modulation, linking biophysical cues to regenerative outcomes. This work pioneers: Injectable thermogelation for minimally invasive DFSC delivery, magnetic guidance directing tissue microarchitecture, and dual-stimuli synergy coupling mechanobiology and immunomodulation. The strategy demonstrates transformative potential for precision periodontal therapy without invasive surgery.