Noncytotoxic zinc-doped nanohydroxyapatite-based bone scaffolds with strong bactericidal, bacteriostatic, and antibiofilm activity.

Development of bone scaffolds that are nontoxic to eukaryotic cells, while revealing bactericidal activity still remains a huge challenge for the scientific community. It should be noted that only bacteriostatic (the ability of the biomaterial to inhibit the growth of bacteria) and bactericidal (the ability to kill >99.9 % bacteria) activities have clinical importance. Unfortunately, many material scientists are confused with the microbiological definition of antibacterial action and consider biomaterials causing reduction in colony-forming units (CFUs) by 50-80 % as promising antibacterial implants. The aim of this study was to synthesize three variants of Zn-doped hydroxyapatite (HA) nanopowder, which were characterized by different content of Zn and served as a powder phase for the production of novel macroporous chitosan/agarose/nanoHA biomaterials with high antibacterial activity. Within this study, it was proven that the scaffold with a low zinc content (doping level 0.03 mol for 1 mol of HA; 0.2 wt%) revealed the gradual and slow release of the Zn ions, preventing against accumulation of high and toxic concentration of therapeutic agents and providing prolonged antibacterial activity. Moreover, developed biomaterial was nontoxic to human osteoblasts and showed anti-biofilm properties, bactericidal activity (> 99.9 % of bacteria killed) against Staphylococcus epidermidis and Escherichia coli, significant antibacterial activity against Staphylococcus aureus (98.5 % of bacteria killed), and also bacteriostatic activity against Pseudomonas aeruginosa. Thus, the developed Zn-doped HA-based bone scaffold has excellent antibacterial properties without toxicity against eukaryotic cells, being a promising biomaterial for biomedical applications to repair bone defects and prevent post-surgery infections.