Synergic role of zinc and gallium doping in hydroxyapatite nanoparticles to improve osteogenesis and antibacterial activity

Recently, postoperative bone infections have been one of the most crucial challenges for surgeons. This study aims to synergistically promote antibacterial and osteoconductive properties of hydroxyapatite (HAp) nanoparticles through binary doping of Zn²⁺ and Ga³⁺ ions (Zn-Ga:HAp). Zn-Ga:HAp nanopowders with spherical morphology and homogeneous size are synthesized using a simple sol-gel method. Substitution of both zinc and gallium in the structure of HAp results in a gradual decrease in the lattice parameters as doping level increases, limits the growth of HAp particles and reduces its crystallinity. Noticeably, the crystallinity of HAp (85%) reduces to less than 73% (for X_Zn = 0.1), 78% (for X_Ga = 0.4) and 75% (for X_Zn = 0.1 and X_Ga = 0.4). Ion doping also significantly modulate the release of bioactive ions (Ca²⁺, PO₄³⁻, Zn²⁺, Ga³⁺) from the Zn-Ga:HAp depended on the overall amount of Ga and Zn in the HAp, which could mediate the biological responses. Incorporating both Zn²⁺ and Ga³⁺ ions in HAp structure could significantly improve the antibacterial activity of HAp nanopowders against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) with a concentration-dependent effect. Noticeably, Zn-Ga:HAp (X_Zn = 0.1 and X_Ga = 0.4) powder shows the antibacterial activity of more than 68% and 84% against E. coli and S. aureus, respectively, at the concentration of 500 μg/ml, thereby showing excellent antibacterial properties. In addition, Zn-Ga:HAp nanopowders not only do not exhibit any cytotoxicity towards hMSCs, but also show significantly superior osteogenic properties. For instance, Zn-Ga:HAp (X_Zn = 0.1 and X_Ga = 0.4) nanopowders significantly enhance the alkaline phosphatase activity (approximately 2-fold) and mineralization (approximately 3-fold) of hMSCs after 14 days of culture, compared to pure HAp. Overall, Zn-Ga:HAp (X_Zn = 0.1 and X_Ga = 0.4) with desired osteogenesis and antibacterial activity compared to pure HAp, Zn:HAp and Ga:HAp shows promising opportunities for the implant-associated infections and the efficient healing of bone defects.