Gallium-Doped Hydroxyapatite Shows Antibacterial Activity against Pseudomonas aeruginosa without Affecting Cell Metabolic Activity

Marika Mosina; Claudia Siverino; Liga Stipniece; Artemijs Sceglovs; Renats Vasiljevs; T Fintan Moriarty; Janis Locs

doi:10.3390/jfb14020051

Gallium-Doped Hydroxyapatite Shows Antibacterial Activity against Pseudomonas aeruginosa without Affecting Cell Metabolic Activity

J Funct Biomater. 2023 Jan 17;14(2):51. doi: 10.3390/jfb14020051.

Authors

Marika Mosina^{1

2}, Claudia Siverino³, Liga Stipniece^{1

2}, Artemijs Sceglovs^{1

2}, Renats Vasiljevs^{1

2}, T Fintan Moriarty³, Janis Locs^{1

2}

Affiliations

¹ Rudolfs Cimdins Riga Biomaterials Innovation and Development Centre, Institute of General Chemical Engineering, Faculty of Materials Science and Applied Chemistry, Riga Technical University, Pulka 3, LV-1007 Riga, Latvia.
² Baltic Biomaterials Centre of Excellence, Headquarters at Riga Technical University, LV-1048 Riga, Latvia.
³ AO Research Institute Davos, 7270 Davos, Switzerland.

Abstract

Calcium phosphates (CaPs) have been used in bone regeneration for decades. Among the described CaPs, synthetic hydroxyapatite (HAp) has a chemical composition similar to that of natural bone. Gallium-containing compounds have been studied since the 1970s for the treatment of autoimmune diseases and have shown beneficial properties, such as antibacterial activity and inhibition of osteoclast activity. In this study, we synthesized hydroxyapatite (HAp) powder with Ga doping ratios up to 6.9 ± 0.5 wt% using the wet chemical precipitation method. The obtained products were characterized using XRD, BET, FTIR, and ICP-MS. Ga³⁺ ion release was determined in the cell culture media for up to 30 days. Antibacterial activity was assessed against five bacterial species: Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus pyogenes. The biocompatibility of the GaHAp samples was determined in human fibroblasts (hTERT-BJ1) through direct and indirect tests. The structure of the synthesized products was characteristic of HAp, as revealed with XRD and FTIR, although the addition of Ga caused a decrease in the crystallite size. Ga³⁺ was released from GaHAp paste in a steady manner, with approximately 40% being released within 21 days. GaHAp with the highest gallium contents, 5.5 ± 0.1 wt% and 6.9 ± 0.5 wt%, inhibited the growth of all five bacterial species, with the greatest activity being against Pseudomonas aeruginosa. Biocompatibility assays showed maintained cell viability (~80%) after seven days of indirect exposure to GaHAp. However, when GaHAp with Ga content above 3.3 ± 0.4 wt% was directly applied on the cells, a decrease in metabolic activity was observed on the seventh day. Overall, these results show that GaHAp with Ga content below 3.3 ± 0.4 wt% has attractive antimicrobial properties, without affecting the cell metabolic activity, creating a material that could be used for bone regeneration and prevention of infection.

Keywords: antibacterial properties; biocompatibility; calcium phosphate; gallium.

Grants and funding

This work was funded by the EuroNanoMedIII project “NANO delivery system for one-shot regenerative therapy of peri-implantis” (ImplantNano, GA.ES RTD/2020/19) and the European Union’s Horizon 2020 research and innovation program under grant agreement No. 857287.