4D-printed Fe3O4-PLLA scaffolds modulate osteoimmune microenvironment for oral bone repair

Craniomaxillofacial bone repair remains a major clinical challenge. Conventional static scaffolds, which retain a fixed geometry after implantation, lack adaptability to complex and irregular defects. In contrast, 4D-printed shape-memory polymer (SMP) scaffolds enable minimally invasive delivery and stimuli-responsive shape adaptation <i>in vivo</i>. When combined with traditional Chinese medicinal monomers, these scaffolds circumvent the immunogenicity of conventional growth factors, reduce treatment costs, and facilitate slow release when loaded into a hydrogel. In this study, naringin-loaded methacrylated chitosan (CSMA) was integrated with 4D-printed Fe₃O₄-PLLA scaffolds to construct hybrid systems featuring long-term drug release and magnetically controlled shape transformation. The resulting scaffolds exhibited excellent magnetic responsiveness, biocompatibility, mechanical robustness, and rapid shape recovery. They exhibited over 98 % shape recovery with rapid recovery time (<40s), indicating potential for minimally invasive implantation and new bone formation. Enhanced polarization of M2 macrophages and osteogenic differentiation of bone marrow mesenchymal stem cells (rBMSCs) were confirmed <i>in vitro</i>. Transcriptome analysis revealed downregulation of the NLRP3 inflammasome, supporting M2 macrophage polarization and bone regeneration <i>in vivo</i>. This study illustrates that 4D-printed NG-CSMA/Fe₃O₄-PLLA scaffolds promote bone regeneration through the polarization of macrophages towards the M2 phenotype, presenting potential strategies for the development of functional scaffolds in bone defect repair.