Controllable Fabrication of Highly Elastic and Drug-Loading Alginate-Chitosan Composite Embolic Microspheres

Transcatheter arterial embolization (TAE) is a minimally invasive therapeutic strategy for treating hypervascular tumors, which relies on the intravascular delivery of embolic agents to obstruct blood supply. Embolic microspheres have emerged as promising agents due to their spherical shape and uniform size, which ensure predictable occlusion levels and targeted delivery. There is a pressing need for a controllable strategy to engineer multifunctional embolic microspheres.

A novel droplet microfluidics-based method for the controllable fabrication of monodisperse alginate-chitosan composite (ACC) microspheres was developed. The mechanical and drugloading properties of the ACC microspheres were systematically characterized. The embolization performance of the optimized microspheres was visually evaluated in a microvascular chip model.

The microfluidic platform enabled the generation of highly monodisperse emulsion templates, leading to ACC microspheres with excellent size uniformity. Mechanical characterization revealed that the elasticity of the microspheres could be finely tuned, allowing for the production of highly elastic microspheres suitable for catheter injection. The ACC microspheres demonstrated favorable drug-loading capacity and sustained release characteristics. In the in vitro chip, the microspheres exhibited superior embolization performance.

The successful fabrication of monodisperse ACC microspheres underscores the precision of droplet microfluidics in creating complex biomaterial structures. The high elasticity is particularly critical for clinical embolization, as it prevents catheter clogging and ensures deep, uniform vessel occlusion. The demonstrated drug-loading capability positions these ACC microspheres as effective drug-eluting beads (DEBs) for combined embolization and local chemotherapy. The visual confirmation of effective embolization in the in vitro chip validates the functional performance of the microspheres.

This study presents a robust microfluidic strategy for the controllable synthesis of monodisperse alginate-chitosan composite microspheres with tunable elasticity and favorable drugloading properties. The fabricated microspheres demonstrated excellent embolization performance in an in vitro model, validating their potential as advanced embolic agents. The findings offer valuable insights and a practical methodology for the rational design and preparation of next-generation multifunctional microspheres, which are highly desired for applications in embolization therapy.