#6768 TIO2/TI3C2 NANOCOMPOSITES FOR BILIRUBIN CLEARANCE FROM BLOOD

Abstract

Abstract Background and Aims The artificial liver treatment based on blood purification is an important and commonly used treatment for liver failure. Aggressive management of hyperbilirubinemia is one of the key steps to reduce mortality in patients with liver failure. Herein, targeting bilirubin in nano-sized, we synthesized a TiO2/Ti3C2 nanocomposite from Ti3C2 MXenes via hydrothermal oxidation for bilirubin clearance from whole blood. Method Firstly, Ti3C2 MXene was prepared by hydrofluoric acid etching method reported in our previous work [1]. Then, it was transferred into Teflon-lined stainless-steel autoclaves (2 mg/ml, 30 ml) and was undergone the hydrothermal process at 180 °C for 6 h and 12 h. TiO2/Ti3C2 nanocomposites were obtained after lyophilization. Hemocompatibility evaluation assays include hemolysis ratio test, complement activation (human complement fragment 5a (C5a)), contact activation (Thrombin–anti-thrombin (TAT) complex) and platelet activation (platelet factor 4 (PF 4)) were systemically conducted in vitro to evaluate the feasibility of the novel nanocomposites (0.5 mg/ml) in contact with blood. We evaluated the bilirubin adsorption capacity of original Ti3C2 (0 h) and TiO2/Ti3C2 (6 h and 12 h) at the concentration of 0.5 mg/ml, respectively, in bilirubin solution (250 mg/l, 10 ml) for 2 h at 37 °C in an air bath away from light. The sphere-forming properties of TiO2/Ti3C2 with polyethersulfone (PES), a commonly used blood purification material, were first verified using a liquid-liquid inversion method. Results TiO2/Ti3C2 (6 h and 12 h) showed better hemocompatibility than the original Ti3C2 (0 h) (Figure 1). The bilirubin adsorption capacities by the original Ti3C2 (0 h) and TiO2/Ti3C2 (6 h and 12 h) were 354.11 mg/g, 492.83 mg/g and 492.52 mg/g, respectively. From the original Ti3C2 (0 h) to TiO2/Ti3C2 (6 h), the clearance rate of bilirubin improved from 70.82% to 98.57%. Therefore, we chose TiO2/Ti3C2 (6 h) to verify the sphere-forming properties of TiO2/Ti3C2 with PES. TiO2/Ti3C2-PES spheres were constructed successfully by a liquid-liquid inversion method. More 3D porous structure on the surface and uniform distribution of TiO2/Ti3C2 (Ti element) in the substrate were observed via a scanning electron microscope (SEM) images and energy dispersive spectroscopy (EDS) mapping images (Figure 2). Conclusion The TiO2/Ti3C2 nanocomposite showed excellent bilirubin clearance capability, superior hemocompatibility, and the great application potential in the form of spheres for hemoperfusion, which may provide a promising choice in the performance enhancement of artificial liver characterized by bilirubin clearance. Importantly, the above properties are adjustable by the heating temperature and the time period, other application forms and strategies of the TiO2/Ti3C2 nanocomposite to target bilirubin in nano-sized are worth being explored and expected.