Bioinspired oriented calcium phosphate nanocrystal arrays with bactericidal and osteogenic properties

The global diffusion of antibiotic resistance poses a severe threat to public health. Addressing antibiotic- resistant infections requires innovative approaches, such as antibacterial nanostructured surfaces (ANSs). These surfaces, featuring ordered arrays of nanostructures, exhibit the ability to kill bacteria upon con- tact. However, most currently developed ANSs utilize bioinert materials, lacking bioactivity crucial for promoting tissue regeneration, particularly in the context of bone infections. This study introduces ANSs composed of bioactive calcium phosphate nanocrystals. Two distinct ANSs were created through a biomineralization-inspired growth of amorphous calcium phosphate (ACP) precursors. The ANSs demon- strated efficient antibacterial properties against both Gram-negative ( P. aeruginosa ) and Gram-positive ( S. aureus ) antibiotic resistant bacteria, with up to 75 % mortality in adhered bacteria after only 4 h of con- tact. Notably, the ANS featuring thinner and less oriented nano-needles exhibited superior efficacy at- tributed to simultaneous membrane rupturing and oxidative stress induction. Moreover, the ANSs facili- tate the proliferation of mammalian cells, enhancing adhesion, spreading, and reducing oxidative stress. The ANSs displayed also significant bioactivity towards human mesenchymal stem cells, promoting col- onization and inducing osteogenic differentiation. Specifically, the ANS with thicker and more ordered nano-needles demonstrated heightened effects. In conclusion, ANSs introduced in this work have the potential to serve as foundation for developing bone graft materials capable of eradicate site infections while concurrently stimulating bone regeneration. Statement of significance Nanostructured surfaces with antibacterial properties through a mechano-bactericidal mechanism have shown significant potential in fighting antibiotic resistance. However, these surfaces have not been fab- ricated with bioactive materials necessary for developing devices that are both antibacterial and able to stimulate tissue regeneration. This study demonstrates the feasibility of creating nanostructured sur- faces of ordered calcium phosphate nano-needles through a biomineralization-inspired growth. These sur- faces exhibit dual functionality, serving as effective bactericidal agents against Gram-negative and Gram- positive antibiotic-resistant bacteria while also promoting the proliferation of mammalian cells and in- ducing osteogenic differentiation of human mesenchymal stem cells. Consequently, this approach holds promise in the context of bone infections, introducing innovative nanostructured surfaces that could be utilized in the development of antimicrobial and osteogenic grafts.