Antibiotics are one of the most successful chemotherapy forms in medicine history. However, the antimicrobial resistance is a global public health issue that can be accelerated by the worldwide antibiotics’ over-use.  Concerning bone implantation scaffold, major post-operative problems are related to infections that can lead to implant failure. Moreover, the treatment of infected bone tissue involves the systemic administration of high dose of antibiotics, that can contribute to antibiotic resistance.
Hydroxyapatite (HA)-based biomaterials are widely regarded as a gold standard for bone regeneration due to their high biomimicry with the mineral phase of bone, which is a key aspect of promoting bone formation. However, stoichiometric hydroxyapatite has limited antibacterial resistance, in respect to ion-doped apatites which previously showed enhanced biomimicry and antibacterial properties, also related to co-substitution with carbonate ions. In this regard, doping apatite structure with Mg²⁺ increases the protein adsorption, cell adhesion, bone growth and can promote angiogenesis, whereas increasing the antibacterial ability. On the other hand, the incorporation of Ag⁺ ions replacing Ca²⁺ has been previously attempted to enhance antibacterial properties, due to the ability of silver ions to interfere with the electron transfer process on bacterial membranes thus causing cell death, whereas it is biocompatible and non-toxic to human cell at low concentration. However, the attainment of a single-phase silver-doped hydroxyapatite is not easy, as Ag has the tendency to crystallize as cytotoxic silver oxides such as Ag₂O and AgO, rather than entering into the apatite lattice. In this respect, the synthesis conditions can play a relevant role to control the pathway of hydroxyapatite crystallization and promote effective ion doping.
Targeting the achievement of single-phase silver-doped hydroxyapatite (HA), in the present work we carried out a synthesis process by wet neutralization method, controlling the kinetics of HA crystallization through process parameters such as the used reactants and relative molar ratios, dripping rate, synthesis temperature, maturation time. In addition, we introduced co-doping with CO₃ ions in the phosphate site (B-carbonation), which may induce crystal disordering in the HA crystal and increase the bioactive and antibacterial properties of the final material. In particular, the molar ion doping of Ag⁺ with respect to calcium was 0%, 5% and 10%, while the CO₃^2- with respect to phosphate was 0% and 15%, with the Ca/P ratio ranging from 1.50 to 1.67.
The obtained materials were characterized in terms of chemical and phase composition, surface area, ion release behaviour, surface morphology and antibacterial properties. Particularly, the evaluation of the ion release kinetics can help to evaluate the specific effect of released silver species on bacterial viability and, also, to give information about the actual presence of silver ion in the HA lattice. The results obtained showed the possibility of obtaining an antimicrobial single-phase multi-ion doped hydroxyapatite.