Preparation of porous TC4 bone scaffold VEGF-Si/HA-TiO2 nanotube composite coating: crystal structure improvement and bio sustained release promoting angiogenesis and osteogenic regeneration

Abstract

Titanium-based porous implants achieve personalized structural matching and provide strong load-bearing capacity, which has led to their widespread application in bone repair. Epidemiological studies report that 5–10 % of orthopedic and dental implants fail within 10–15 years after surgery, mainly due to aseptic loosening caused by poor osteogenesis and vascularization. To address this issue, this study proposes a strategy for preparing functionalized coatings on the surface of titanium-based scaffolds to promote the dual regeneration of vascular and bone tissues. By adjusting the composition of different electrolytes, a silicon-doped hydroxyapatite (Si/HA) coating was successfully prepared on titanium dioxide nanotubes (TNTs), which subsequently served as a platform for VEGF loading. The study showed that he TiO₂ nanotubes formed on the porous micro-curved surface exhibited an average diameter of 180 nm and a length of 7.56 μm. By adding sodium silicate to the electrolyte, compared to pure HA crystals, the Si/HA crystals transformed from an irregular morphology to a columnar and vertically aligned crystal structure with respect to the substrate, which enhanced the mechanical interlocking behavior of the composite coating. Additionally, the increased surface charge of the Si/HA coating markedly enhanced its electrostatic adsorption capacity for VEGF, enabling controlled release rates. After 28 days, VEGF release followed a sustained-release profile, reaching 1.22 μg/ml. Cellular experiments confirmed that the synergistic release of VEGF and Si markedly promoted the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVEC). ALP、OCN and Runx2 activity analysis indicated that the bioactivity of the VEGF-Si/HA-TNTs coating was significantly higher than that of the other two groups on days 7 and 14. This study provides new insights into the functionalization of titanium-based implant coatings, highlighting their potential to improve clinical outcomes in bone repair, particularly through enhanced angiogenesis and osteogenesis.