Dual-release 3D-printed porous Ti-6Al-4V implant with drug-eluting photothermal micro-nanotopographies: combating osteosarcoma recurrence, infections, and enhancing osteogenesis

Abstract

3D-printed porous Ti-6Al-4V implants are widely used in bone defect repair following osteosarcoma resection due to their favorable mechanical properties and biocompatibility. However, eliminating residual tumor cells, preventing bacterial infection, and ensuring effective osseointegration remain key challenges. In this paper, the implant containing a dual-release system was developed. First, a primary drug reservoir was constructed using nanotubes loaded with ZnO and rare earth elements (Y, Yb, Er). Second, a secondary phototherapy platform was created by coating the reservoir with a gelatin/sodium alginate hydrogel containing MgO₂, curcumin, and paclitaxel. Flow acid etching and anodic oxidation removed residuals and formed TiO₂ nanotube arrays, while rare earth doping enhanced upconversion capability. Under 808 nm near-infrared irradiation (NIR), localized photothermal heating (54 °C) triggered hydrogel degradation, releasing the contents. Subsequently, the primary reservoir facilitated sustained Zn²⁺ release alongside micro-nano cues. The modified surface demonstrated improved wettability and superior corrosion resistance. Meanwhile, the hydrogel exhibited near-complete degradation (95 %) within 21 days, corresponding to the optimal therapeutic window following tumor resection. The biological experiments demonstrated that the dual-release system systematically inhibited tumor growth, eradicated bacterial infections, and promoted osteogenesis. Furthermore, this system modulated intracellular signaling pathways in both bone marrow mesenchymal stem cells (MSCs) and osteosarcoma cells (HOS). The system orchestrated metabolic reprogramming and modulated organelle dynamics. These coordinated effects simultaneously enhanced MSCs' osteogenic differentiation while inducing apoptosis in HOS. Furthermore, the system potentiated reactive oxygen species (ROS) production, amplifying oxidative stress in bacterial populations. This strategy presents a therapeutic approach for post-resection osteosarcoma management.

Keywords: Anti-tumor; Antibacterial; Dual-release system; Metabolic reprogramming; Osteogenesis; Signal pathway.