Multifunctional 3D-Printed Titanium Alloy Composite-Coated Scaffold for Modulating the Immune Microenvironment and Promoting Osteogenesis

Bone tissue engineering has advanced with the development of biomaterials that not only provide structural support but also modulate biological responses for enhanced tissue regeneration. In this study, we developed a cytokine-functionalized Zn-incorporated titanium scaffold (IL4/IL13@SM@pTi-Zn) to improve bone regeneration through immune modulation and osteogenesis. The scaffold exhibited excellent biocompatibility and significantly promoted osteogenic differentiation of mouse bone marrow mesenchymal stem cells. Quantitative polymerase chain reaction analysis showed that the expression of key osteogenic genes was markedly upregulated, with alkaline phosphatase, COL1A1, Runx2, and OPN increasing by 148%, 198%, 250%, and 245%, respectively, compared with the unmodified pTi group. In addition, the scaffold effectively reduced pro-inflammatory marker expression and intracellular reactive oxygen species accumulation, indicating favorable immunomodulatory and antioxidant effects. In vivo evaluation in a rabbit femoral condyle defect model further demonstrated enhanced bone regeneration. Micro-CT analysis revealed that bone volume fraction (BV/TV) increased by 14.8% at 4 weeks and 18.3% at 8 weeks, while trabecular thickness (Tb.Th) increased by 21.3% and 22.2%, respectively, compared to the control group. Collectively, these findings demonstrate that IL4/IL13@SM@pTi-Zn enhances bone repair through the synergistic promotion of osteogenesis and immune regulation, highlighting its potential as a promising biomaterial for bone defect repair.