4D-Printed Magnetically Responsive Scaffolds For Immunomodulatory Oral Bone Regeneration

This study developed a magnetically responsive 4D-printed scaffold to achieve immunomodulatory osteogenesis and dynamic bone remodeling for oral defect repair through programmable shape adaptation and macrophages-BMSCs interactions. A hybrid Fe₃O₄/PLLA/CSMA/NG scaffold was fabricated via 3D printing and smart materials. In vitro: A BMSCs-macrophages co-culture system was established to evaluate osteogenic differentiation (ALP activity, alizarin red staining, RT-PCR and WB for Runx2/OCN/BMP2) and macrophage polarization (flow cytometry for CD86/CD206, ELISA, RT-PCR, WB, RNA-seq). In vivo: Mandibular bone defects in SD rats (n=5/group) were treated with magnetically activated scaffolds. Bone regeneration was assessed via micro-CT (BMD, BV/TV, trabecular parameters) and histology (H&E, Masson and immunohistochemical staining). All animal experiments were performed in accordance with procedures approved by the Animal Care and Use Committee. The scaffold achieved 80% shape recovery within 2 minutes under magnetic actuation. NG synergized with M2 macrophages to enhance BMSC osteogenic differentiation and mineralization. Transcriptomic analysis revealed key osteo-immunomodulatory differentially expressed genes. Scaffold-treated defects showing significantly higher BV/TV than controls (p<0.05). This 4D-printed scaffold integrates magnetic-driven dynamic remodeling with macrophage-mediated osteoinduction, offering a innovative strategy for immunomodulation and functional oral bone regeneration in oral rehabilitation.