Synergistic anti-infection and osteogenesis via a 3D-printed titanium scaffold with kanamycin sulfate–loaded hydrogel sustained-release system for infected-bone regeneration

BACKGROUND: The treatment of infected bone defects remains challenging due to persistent infection, insufficient local drug delivery, and a disrupted repair microenvironment. Conventional porous titanium (Ti) scaffolds lack antibacterial functionality, while systemic antibiotics often fail to achieve adequate local concentrations. To address these limitations, this study designed a composite scaffold integrating localized sustained-release antibacterial capability and mechanical compatibility. METHODS: A gyroid porous Ti scaffold with ∼74% porosity and ∼0.82 mm pore size was fabricated via selective laser melting. It was subsequently infused with a sodium alginate/gelatin (SG) hydrogel loaded with kanamycin sulfate (KS) at concentrations of 2.5, 5.0, and 10.0 mg/mL, forming Ti@SG + KS2.5, Ti@SG + KS5, and Ti@SG + KS10 composite scaffolds. These were characterized for microstructure, mechanical properties, drug release, antibacterial activity, and biocompatibility through in vitro and in vivo evaluations, including antibacterial and antibiofilm assays, cell-migration and tube-formation tests, subcutaneous implantation, and an infected bone defect model in rats. RESULTS: The composite scaffolds retained an open gyroid pore structure with mechanical properties suitable for bone repair, exhibiting compressive yield strengths of 27.9-29.2 MPa and elastic moduli of 0.55-0.58 GPa. The Ti@SG + KS10 scaffold demonstrated strong and sustained antibacterial and antibiofilm activity against Escherichia coli and Staphylococcus aureus, promoted collagen deposition, and suppressed excessive inflammation. In a rat infected bone defect model, it effectively eradicated local infection and significantly enhanced trabecular bone formation, with bone volume and maturity markedly exceeding those of the pure Ti control, along with notable systemic biosafety. SIGNIFICANCE: This study successfully developed a multifunctional Ti‑based composite scaffold that provides mechanical support, localized sustained antibacterial release, and osteogenic enhancement. The scaffold effectively addresses key challenges in the repair of infected bone, such as infection control and microenvironment regulation, thereby offering a promising integrated strategy for the clinical management of infected bone defects.