Microfluidic fabrication of X-ray-visible sodium hyaluronate microspheres for embolization

Catheter embolization is a minimally invasive technique that relies on embolic agents and is now widely used to treat various high-prevalence medical diseases. Embolic agents usually need to be combined with exogenous contrasts to visualize the embolotherapy process. However, the exogenous contrasts are quite simply washed away by blood flow, making it impossible to monitor the embolized location. To solve this problem, a series of sodium hyaluronate (SH) loaded with bismuth sulfide (Bi₂S₃) nanorods (NRs) microspheres (Bi₂S₃@SH) were prepared in this study by using 1,4-butaneglycol diglycidyl ether (BDDE) as a crosslinker through single-step microfluidics. Bi₂S₃@SH-1 microspheres showed the best performance among other prepared microspheres. The fabricated microspheres had uniform size and good dispersibility. Furthermore, the introduction of Bi₂S₃ NRs synthesized by a hydrothermal method as Computed Tomography (CT) contrast agents improved the mechanical properties of Bi₂S₃@SH-1 microspheres and endowed the microspheres with excellent X-ray impermeability. The blood compatibility and cytotoxicity test showed that the Bi₂S₃@SH-1 microspheres had good biocompatibility. In particular, the in vitro simulated embolization experiment results indicate that the Bi₂S₃@SH-1 microspheres had excellent embolization effect, especially for the small-sized blood vessels of 500-300 and 300 μm. The results showed the prepared Bi₂S₃@SH-1 microspheres have good biocompatibility and mechanical properties, as well as certain X-ray visibility and excellent embolization effects. We believe that the design and combination of this material has good guiding significance in the field of embolotherapy.