This paper presents the development of advanced Ti implants with enhanced antibacterial activity. The implants were engineered using additive manufacturing three-dimensional (3D) printing technology followed by surface modification with electrochemical anodization and hydrothermal etching, to create unique hierarchical micro/nanosurface topographies of microspheres covered with sharp nanopillars that can mechanically kill bacteria in contact with the surface. To achieve enhanced antibacterial performance, fabricated Ti implant models were loaded with gallium nitrate as an antibacterial agent. The antibacterial efficacy of the fabricated substrates with the combined action of sharp nanopillars and locally releasing gallium ions (Ga 3+ ) was evaluated toward Staphylococcus aureus and Pseudomonas aeruginosa. Results confirm the significant antibacterial performance of Ga 3+ -loaded substrates with a 100% eradication of bacteria. The nanopillars significantly reduced bacterial attachment and prevented biofilm formation while also killing any bacteria remaining on the surface. Furthermore, 3Dprinted surfaces with microspheres of diameter 5−30 μm and interspaces of 12−35 μm favored the attachment of osteoblast-like MG-63 cells, as confirmed via the assessment of their attachment, proliferation, and viability. This study provides important progress toward engineering of next-generation 3D-printed implants, that combine surface chemistry and structure to achieve a highly efficacious antibacterial surface with dual cytocompatibility to overcome the limitations of conventional Ti implants.

Despite recent advances in the development of orthopedic devices, implant-related failures that occur as a result of poor osseointegration and nosocomial infection are frequent. In this study, we developed a multiscale titanium (Ti) surface topography that promotes both osteogenic and mechanobactericidal activity using a simple two-step fabrication approach. The response of MG-63 osteoblast-like cells and antibacterial activity toward Pseudomonas aeruginosa and Staphylococcus aureus bacteria was compared for two distinct micronanoarchitectures of differing surface roughness created by acid etching, using either hydrochloric acid (HCl) or sulfuric acid (H 2 SO 4 ), followed by hydrothermal treatment, henceforth referred to as either MN-HCl or MN-H 2 SO 4 . The MN-HCl surfaces were characterized by an average surface microroughness (S a ) of 0.8 ± 0.1 μm covered by blade-like nanosheets of 10 ± 2.1 nm thickness, whereas the MN-H 2 SO 4 surfaces exhibited a greater S a value of 5.8 ± 0.6 μm, with a network of nanosheets of 20 ± 2.6 nm thickness. Both micronanostructured surfaces promoted enhanced MG-63 attachment and differentiation; however, cell proliferation was only significantly increased on MN-HCl surfaces. In addition, the MN-HCl surface exhibited increased levels of bactericidal activity, with only 0.6% of the P. aeruginosa cells and approximately 5% S. aureus cells remaining viable after 24 h when compared to control surfaces. Thus, we propose the modulation of surface roughness and architecture on the micro-and nanoscale to achieve efficient manipulation of osteogenic cell response combined with mechanical antibacterial activity. The outcomes of this study provide significant insight into the further development of advanced multifunctional orthopedic implant surfaces.