Combined release of LL37 peptide and zinc ion from a mussel-inspired coating on porous titanium for infected bone defect repairing

Implant-associated infections impose great burden on patient health and public healthcare. Antimicrobial peptides and metal ions are generally incorporated onto implant surface to deter bacteria colonization. However, it is still challenging to efficiently prevent postoperative infections at non-cytotoxic dosages. Herein, a scaffold based on porous titanium coated with a mussel-inspired dual-diameter TiO₂ nanotubes is developed for loading dual drugs of LL37 peptide and Zn²⁺ with different sizes and characteristics. Benefiting from in-situ formed polydopamine layer and dual-diameter nanotubular structure, the scaffold provides an efficient platform for controllable drugs elution: accelerated release under acidic condition and sustained release for up to 28 days under neutral/alkalescent circumstances. Such combination of dual drugs simultaneously enhanced antibacterial efficacy and osteogenesis. In antibacterial test, LL37 peptide serving as bacteria membrane puncture agent, and Zn²⁺ acting as ROS generator, cooperatively destroyed bacterial membrane integrity and subsequently damaged bacterial DNA, endowing dual-drug loaded scaffold with remarkable bactericidal efficiency of > 92 % in vitro and > 99 % in vivo. Noteworthily, dual-drug loaded scaffold promoted bone-implant osteointegration under infectious microenvironment, overmatching single-drug load ones. It provides a promising strategy on surface modification of implant for infected bone defect repairing.