A multifunctional EGCG/Si nanohybrid-coated 3D-printed porous scaffold for bone defect repair

Besides enhancing osteogenesis and angiogenesis, designing multifunctional scaffolds with immunomodulatory capabilities offers a promising strategy for managing bone defects. Herein, a 3D-printed scaffold modified with inorganic silicon (Si) ions and the polyphenol epigallocatechin gallate (EGCG) was constructed as an immunomodulatory biocomposite with coupled angiogenic and osteogenic activity to enhance bone regeneration. Through phenol-amine chemistry and electrostatic layer-by-layer deposition, a nanohybrid EGCG/Si coating was fabricated on the poly(lactic-co-glycolic acid) scaffold surface. Our in vitro studies demonstrated that the released Si ions, in combination with the surface topological morphology, promoted osteogenic differentiation of bone mesenchymal stem cells and enhanced the ability of human umbilical endothelial cells to form patterned vascular networks. The EGCG-coated scaffold not only provides effective protection against reactive oxygen species-mediated cellular damage but also actively modulates the immune microenvironment by inducing macrophage polarization toward a reparative phenotype, enhancing the expression of anti-inflammatory factors and inhibiting pro-inflammatory gene expression. In vivo experiments further revealed that the coated scaffolds exhibited significant potential in enhancing new bone formation within rat femoral defects. Transcriptomic profiling indicated that Si ions, in conjunction with surface topography, cooperatively triggered multiple signaling pathways involved in cell adhesion, proliferation and differentiation. Overall, this EGCG/Si nanocomposite coating approach presents a novel avenue for developing multifunctional scaffolds in bone tissue engineering.