Sifeng Shi, Siyuan He, Qiang Lin, Shaosong Sun
Abstract: Orthopedic regenerative medicine faces significant challenges in treating critical-sized bone defects, infections, and achieving spatiotemporal therapeutic control. Traditional hydrogels, while providing a biocompatible three-dimensional (3D) environment, often lack the dynamic responsiveness and mechanical strength required for effective bone repair. The integration of magnetic nanoparticles (MNPs), particularly iron oxides (Fe 3 O 4 , γ-Fe 2 O 3 ), into hydrogel matrices has emerged as a transformative strategy to overcome these limitations. These magnetic nanocomposite hydrogels (MNHs) leverage the unique superparamagnetic properties of MNPs to enable remote and non-invasive control over their structure and function via external magnetic fields. This review comprehensively explores the design principles, synthesis methodologies, and multifaceted applications of MNHs in orthopedics. Key advancements discussed include their role in enhancing targeted drug delivery (eg, on-demand antibiotic or growth factor release), facilitating cell-based therapies through magnetic retention and mechanostimulation of mesenchymal stem cells (MSCs), and serving as dynamic scaffolds for bone tissue engineering with improved osteogenic commitment. Furthermore, MNHs exhibit great promise in anti-infective therapies by leveraging magnetic hyperthermia to eradicate biofilms and in diagnostic monitoring as contrast agents for MR. Despite their immense potential, clinical translation is contingent upon addressing critical challenges such as long-term biocompatibility of MNPs, scalability of fabrication, and achieving precise in vivo control of magnetic fields. Future perspectives highlight the convergence of MNHs with 4D bioprinting and artificial intelligence (AI) for designing patient-specific, intelligent systems. This review concludes that MNHs represent a paradigm shift towards personalized and adaptive regenerative solutions, poised to redefine treatment strategies in orthopedics and beyond. Keywords: magnetic nanoparticles, hydrogels, bone regeneration, drug delivery, orthopedic infection