The discovery of antibiotics represented a major medical progress that granted a significant improvement of human life in a relatively short amount of time. Nevertheless, after decades of misuse (linked not only to the public but also to their intensive use in agriculture and farming) the advent of Anti-Microbial Resistant (AMR) bacterial strains poses a major public health challenge. The ECDC foresees that AMR-related diseases will be responsible for more deaths than cancers by 2050 [1]. Furthermore, as per the previsions of the World Bank, they will have an economic impact on healthcare systems comparable to the Economic Crisis of 2008 [2]. This threat becomes particularly challenging when considering invasive surgeries as in orthopedics, where the increase of post-operative infections is significant and where the demand for alternatives to antibiotics is higher. This background led to the creation of the AIMed (Antimicrobial Integrated Methodologies for orthopaedic applications: www.aimed-itn.eu) European Innovative Training Network (H2020). This European network, including this research work, focuses on the development of innovative materials with antibacterial properties for use as orthopedic bioactive implants.
The main concept of the present work is related to the realization of smart calcium phosphate (CaP)-based biomaterials combined with non-antibiotic antimicrobial agents. The preferred CaP in this work are biomimetic apatites; these materials are interesting not only because of their properties extremely close to the ones of the bone mineral, but also because of the possibility to substitute Ca2+ with bioactive ions such as Ag+, Cu2+ or Zn2+. These ions can provide not only antimicrobial properties but can also stimulate the bone formation [3] or the formation of new blood vessels [4]. Furthermore, a key aspect of this study is to achieve a controlled distribution of these doping ions, thus aiming a control of their release after implantation. To this aim, we developed an innovative strategy based on 3-fluid nozzle spray drying, starting from apatite gels, and leading to spherical core-shell particles [5].              
Different combinations of substituting ions were tested, involving in particular an antibacterial ion in the outer shell and an osteogenic/proangiogenic ion in the inner core; and all particles were characterized by FTIR, XRD and AAS. FE-SEM analyses with FIB milling coupled with EDX were performed to differentiate the ionic composition of the particles core and shell. The particles are also currently tested for their cytotoxicity, their potential antimicrobial activity and for their mechanism of ion release in different conditions.
These novel particles could find applications in bone engineering, whether in the constitution of low temperature coatings on metal substrates or for the realization of scaffolds, e.g. by freeze casting in association with a polymer porous matrix.

References:
[1] European Commission. A European One Health Action Plan against Antimicrobial Resistance (AMR); European Commission: Brussels, Belgium, 2017.
[2] O’Neill, J. Tackling Drug-Resistant Infections Globally: Final Report and Recommendations. 2016. Available online: https://amr-review.org/sites/default/files/160525_Final%20paper_with%20cover.pdf
[3] Elrayah, A. et al. Materials 2018, 11, 1516.
[4] Lowe, N.M.et al. Proc. Nutr. Soc. 2002, 61, 181–185.
[5] Cianflone, E. et al. Nanomaterials 2023, 13(3), 519