Hydrogen has been used to suppress tumor growth with considerable efficacy. Inhalation of hydrogen gas and oral ingestion of hydrogen-rich saline are two common systemic routes of hydrogen administration. We have developed a topical delivery method of hydrogen at targeted sites through the degradation of magnesium-based biomaterials. However, the underlying mechanism of hydrogen's role in cancer treatment remains ambiguous. Here, we investigate the mechanism of tumor cell apoptosis triggered by the hydrogen released from magnesium-based biomaterials. We find that the localized release of hydrogen increases the expression level of P53 tumor suppressor proteins, as demonstrated by the in vitro RNA sequencing and protein expression analysis. Then, the P53 proteins disrupt the membrane potential of mitochondria, activate autophagy, suppress the reactive oxygen species in cancer cells, and finally result in tumor suppression. The anti-tumor efficacy of magnesium-based biomaterials is further validated in vivo by inserting magnesium wire into the subcutaneous tumor in a mouse. We also discovered that the minimal hydrogen concentration from magnesium wires to trigger substantial tumor apoptosis is 91.2 μL/mm³ per day, which is much lower than that required for hydrogen inhalation. Taken together, these findings reveal the release of H₂ from magnesium-based biomaterial exerts its anti-tumoral activity by activating the P53-mediated lysosome-mitochondria apoptosis signaling pathway, which strengthens the therapeutic potential of this biomaterial as localized anti-tumor treatment.

A highly ordered TiO ₂ nanotube array has been prepared on a commercial pure titanium substrate in a hydrofluoric (HF) electrolyte using a DC power source through two-step anodic oxidation. The morphology, composition, wettability and surface energy of the nanotube array have been characterized by using a field-emission scanning electron microscope (FE-SEM), a transmission electron microscope (JEM-2010) with energy-dispersive X-ray spectrometer EDX (INCA OXFORD), X-ray diffraction method, an atomic force microscope (AFM), an optical contact angle measuring device and the Owens method with two liquids. The electrochemical behaviours of anodic oxidation films with different structures have been investigated in Sodium Lactate Ringer's Injection at 37±1°C by potentiodynamic polarization curve and electrochemical impedance spectroscopy. The formation mechanism of the nanotube array and the advantages of two-step oxidation have been discussed according to the experimental observation and the characterized results. Meanwhile, the structural changes of nanotubes are analysed according to the results of impedance spectroscopy. Cytotoxicity testing and cell adhesion and proliferation have been studied in order to evaluate the bioactivity of the nanotube array film. The diameters of nanotubes are in the range of 120–140 nm. The nanotube surface shows better wettability and higher surface energy compared to the bare substrate. The nanotube surface exhibits a wide passivation range and good corrosion resistance. The growth of the nanotube array is the result of the combined action of the anodization and field-assisted dissolution. The nanotube array by two-step oxidation becomes more regular and orderly. Moreover, the nanotube array surface is non-toxic and favourable to cell adhesion and proliferation. Such nanotube array films are expected to have significant biomedical applications.