Morphology controlled sodium hyaluronate microspheres via microfluidics for promising transcatheter arterial embolization.

Abstract

Controlling the shape of biopolymer-derived microspheres with potential biodegradability is important for medical applications such as drug delivery, embolization therapy, and tissue engineering; however, establishing clear links between structure and function remains challenging. In this study, we present a microfluidic method for producing sodium hyaluronate microspheres (SH MSs) with adjustable shapes (spherical and bowl-shaped) by precisely regulating the flow rate and polymer concentration. Our parametric analysis indicates that droplet solidification dynamics, influenced by flow rates and polymer concentration, dictate the final morphology. The bowl-shaped microspheres demonstrated higher mechanical stability in single-particle compression tests (Young's modulus = 395 ± 56 kPa, compared with 145 ± 10 kPa for spherical microspheres). Consistent results were observed in rheological measurements. After 72 h of in vitro culture of human umbilical vein endothelial cells (HUVECs), cell viability remained above 90%, indicating no significant cytotoxicity. Their tunable flexibility facilitated complete vascular occlusion in a microfluidic model. In a rabbit VX2 orthotopic liver tumor model, successful embolization and tumor necrosis were achieved. These findings position SH microspheres as promising candidates for embolization therapy; however, further comparative studies with commercial embolic agents and long-term safety assessments are warranted.