Facile synthesis of multi-functional nano-composites by precise loading of Cu2+ onto MgO nano-particles for enhanced osteoblast differentiation, inhibited osteoclast formation and effective bacterial killing

Biomaterials with multi-functions including enhancing osteogenesis, inhibiting osteoclastogenesis and effectively removing bacteria are urgently needed in the treatment of osteoporotic bone defects. In this study, MgO nano-particles were employed as a platform for precise Cu2+ loading. By immersing MgO into CuSO4 solution with a pre-defined concentration (0.1, 1 or 10 mM), 1 mg MgO adsorbed 3.25, 32.5 or 325 μg Cu2+ from the solution. As-synthesized nano-composites were referred as MgO-0.1Cu, MgO-1Cu or MgO-10Cu depending on the concentration of employed CuSO4 solution. The results revealed that MgO-xCu (x = 0.1, 1 and 10) nano-composites were lamella-shaped and composed of amorphous Cu(OH)2, crystalline Mg(OH)2 and minor MgO. The extracellular release of Cu2+ was rather limited due the capture of Cu2+ by Mg(OH)2. In vitro results revealed that MgO-xCu (x = 0.1, 1 and 10) nano-composites modulated osteoblast, osteoclast and bacterium response in a Cu2+ loading amount-dependent manner. MgO-0.1Cu nano-composite exhibited stimulatory function on osteoblast proliferation without influencing osteoblast maturation, osteoclast formation and bacterial survival. MgO-1Cu nano-composite enhanced osteoblast proliferation and differentiation, inhibited osteoclast formation and effectively killed bacteria. When larger amount of Cu2+ was loaded, MgO-10Cu nano-composite exhibited stronger stimulatory effect on osteoblast maturation, enhanced inhibitory function on osteoclast formation and promoted bactericidal performance, although it showed a certain degree of initial cyto-toxicity. Together, the results suggest that MgO nano-particles could be employed as potential platform for precise Cu2+ loading and intracellular Cu2+ delivery. MgO-xCu (x = 1 and 10) nano-composites are promising to be employed as multi-functional fillers in bone tissue engineering scaffolds for osteoporotic bone regeneration.