Rayleigh Instability-Driven Coaxial Spinning of Knotted Cell-Laden Alginate Fibers as Artificial Lymph Vessels

Constructing artificial lymph vessels, which play a key role in the immune response, can provide new insights into immunology and disease pathologies. An immune tissue is a highly complex network that consists of lymph vessels, with a "beads-on-a-string" knotted structure. Herein, we present the facile and rapid fabrication of beads-on-a-string knotted cell-laden fibers using coaxial spinning of alginate by exploiting the Plateau-Rayleigh instability. It is shown how alterations in the flow rate and alginate concentration greatly affect the beads-on-a-string structure, rooted in the Plateau-Rayleigh instability theory. Biocompatibility was confirmed by the lactate dehydrogenase (LDH) assay and live/dead staining of the encapsulated human white blood cells. Finally, the encapsulated white blood cells were still functional as indicated by their anti-CD3 activation to secrete interleukin 2. The rapid fabrication of a cell-laden beads-on-a-string three-dimensional (3D) culture platform enables a crude mimicry of the lymph vessel structure. With joint expertise in immunology, microfluidics, and bioreactors, the technology may contribute to the mechanistic assay of human immune response in vitro and functional replacement.