3D Printed Titanium Scaffolds with Bi‐Directional Gradient QK‐Functionalized Surface

3D printed titanium scaffold has promising applications in orthopedics. However, the bioinert titanium presents challenges for promoting vascularization and tissue growth within the porous scaffold for stable osteointegration. In this study, a modular porous titanium scaffold is created using 3D printing and a gradient-surface strategy to immobilize QK peptide on the surface with a bi-directional gradient distribution. This design featured high peptide density in the interior and low peptide density on both ends, aiming to induce cell migration from ends to interior and subsequently enhance vascularization and osteointegration within the scaffold. In vitro results showed that besides the inherent bioactivity, the gradient distribution of QK positively correlated with endothelial cell migration and promoted angiogenesis. In vivo assay was performed by a segmental bone defect model in rabbit and a spine repair model in sheep. Various staining and Micro-CT results demonstrated that compared to that with uniformly QK-functionalized surface, the scaffold with bi-directional gradient QK-functionalized surface (Ti-G) significantly encouraged new tissue growth toward the interior of the scaffold, subsequently facilitated angiogenesis and osteointegration. This study provides an effective strategy for enhancing the bioactivity of peptide-functionalized scaffolds through the concept of bi-directional gradients, and holds potential for various 3D printed scaffolds.