Superimposed Electric Field Enhanced Electrospray for High-Throughput and Consistent Cell Encapsulation.

ABSTRACT

Cell encapsulation technology, crucial for advanced biomedical applications, faces challenges in existing microfluidic and electrospray methods. Microfluidic techniques, while precise, can damage vulnerable cells, and conventional electrospray methods often encounter instability and capsule breakage during high-throughput encapsulation. Inspired by the transformation of the working state from unstable dripping to stable jetting triggered by local electric potential, this study introduces a superimposed electric field (SEF)-enhanced electrospray method for cell encapsulation, with improved stability and biocompatibility. Utilizing stiffness theory, the stability of the electrospray, whose stiffness is five times stronger under conical confinement, is quantitatively analyzed. The SEF technique enables rapid, continuous production of ≈300 core-shell capsules per second in an aqueous environment, significantly improving cell encapsulation efficiency. This method demonstrates remarkable potential as exemplified in two key applications (1) a 92-fold increase in human-derived induced pluripotent stem cells (iPSCs) expansion over 10 d, outperforming traditional 2D cultures in both growth rate and pluripotency maintenance, and (2) the development of liver capsules for steatosis modeling, exhibiting normal function and biomimetic lipid accumulation. The SEF-enhanced electrospray method presents a significant advancement in cell encapsulation technology. It offers a more efficient, stable, and biocompatible approach for clinical transplantation, drug screening, and cell therapy.