Inflammatory Bone Resorption and Antiosteosarcoma Potentials of Zinc Ion Sustained Release ZnO Chips: Friend or Foe?

Multifunctional zinc oxide (ZnO) has been generated as nanoparticles or nanorods and applied to various medical purposes since it exhibits several biological actions including anticancer activity. Especially, due to antibacterial activity and effects on bone regeneration, ZnO is widely used in implants and scaffolds in the orthopedic and dental fields. However, concerns over side effects have been raised recently in the clinical use of ZnO, and it is necessary to assess the safety of ZnO regarding its inflammatory potential in the bone environment. This made us hypothesize that the inflammatory activity of zinc ions released from ZnO NPs could be harmful to induce bone resorption but that their cytotoxicity would be beneficial to kill osteosarcoma. To clarify this hypothesis, in the present work, the effects of ZnO on bone matrix and abnormal bone environments were investigated quantitatively using ZnO chips, filter paper, or glass slides coated with thin films of ZnO grown via atomic layer deposition (ALD). ALD-grown ZnO thin films exhibit thickness with atomic precision, which enables the quantitative analysis of the effects of ZnO. In vivo application of ZnO chips to mouse calvarial bone induced bone resorption, presumably due to the activation of osteoclasts by zinc ion-induced TNF-α release. However, in vitro application of ZnO chips to osteosarcoma cells induced caspase-dependent apoptosis and oxidative stress. Taken together, the results showed two sides of ZnO as our hypothesis. Therefore, careful design and multiple evaluations for the safety and efficacy of ZnO materials are necessary for its successful clinical application.