Surface Phenomena Enhancing the Antibacterial and Osteogenic Ability of Nanocrystalline Hydroxyapatite, Activated by Multiple-Ion Doping

The present work describes a novel nanocrystalline, multidoped hydroxyapatite featuring excellent eukaryotic versus prokaryotic cell selectivity, attested by excellent osteoinductive character and evaluated with human stem cells, and anti-infective ability, tested against different pathogens. Physicochemical analysis and transmission electron microscopy (TEM)/scanning STEM observations highlighted that such enhanced biological features are related to the lower crystallinity level and increased surface charge of hydroxyapatite, both induced by multiple-ion doping. Specifically, the lattice substitution of Ca²⁺ with Zn²⁺ promotes the segregation of Ca²⁺ and doping Mg²⁺ cations to a less-ordered surface layer, thus promoting dynamic ion absorption/release acting as bioactive signals for cells and exerting an antiproliferative effect on all tested pathogens. These findings open the design of new biodevices, combining regenerative ability and effective microbial inhibition without using any antibiotic drugs. This is extremely important to circumvent bacterial resistance to antibiotics, which is today considered as one of the biggest threats to global health.