Melatonin-loaded mesoporous zinc- and gallium-doped hydroxyapatite nanoparticles to control infection and bone repair

Effective treatment of infected bone defects resulting from multi-drug resistant bacteria (MDR) has emerged as a significant clinical challenge, highlighting the pressing demand for potent antibacterial bone graft substitutes. Mesoporous nanoparticles have been introduced as a promising class of biomaterials offering significant properties for treating bone infections. Herein, we synthesize antibacterial mesoporous hydroxyapatite substituted with zinc and gallium (Zn-Ga:mHA) nanoparticles using a facile sol-gel method. The resulting mesoporous nanoparticles are applied for the controlled release of melatonin (Mel). Zn-Ga:mHA nanoparticles with an average particle size of 36 ± 3 nm and pore size of 10.6 ± 0.4 nm reveal a Mel loading efficiency of 58 ± 1%. Results show that 50% of Mel is released within 20 h and its long-term release is recorded up to 50 h. The Zn-Ga:mHA nanoparticles exhibit highly effective antibacterial performance as reflected by a 19 ± 1% and 8 ± 2% viability reduction in Escherichia coli and Staphylococcus bacteria, respectively. Noticeably, Mel-loaded Zn-Ga:mHA nanoparticles are also cytocompatible and stimulate in vitro osteogenic differentiation of human mesenchymal stem cells (hMSCs) without any osteoinductive factor. In vivo studies in a rabbit skull also show significant regeneration of bone during 14 days. In summary, Mel-loaded Zn-Ga:mHA nanoparticles provide great potential as an antibacterial and osteogenic component in bone substitutes like hydrogels, scaffolds, and coatings.