Encapsulated Arrays of Self-Assembled Microtissues: An Alternative to Spherical Microcapsules

Abstract

Micro-encapsulation and immuno-isolation of allogenic and xenogenic tissues and cells is a promising method for the treatment of a variety of metabolic disorders. Many years have been spent optimizing spherical microcapsules, yet micro-encapsulation has not achieved its full clinical potential. As an alternative to spherical microcapsules, this study presents an alginate-encapsulated array of self-assembled three-dimensional (3D) microtissues. Monodispersed HepG2 cells were seeded onto a micro-molded agarose gel. Cells settled to the bottom of the mold recesses and self-assembled 3D microtissues (n = 822) within 24 h. This array of densely packed microtissues was encapsulated in situ using alginate. When separated from the agarose micro-mold, the encapsulated array had HepG2 microtissues in close proximity to its surface. This surface could be further modified by a simple dipping process. Microtissue size, viability, and albumin secretion were all controllable by the number of cells seeded onto the original agarose micro-mold, and microtissue shape and spacing were controllable by the design of the micro-mold. This approach to encapsulation and the use of self-assembled/self-packing 3D microtissues offers new design possibilities that may help to address certain limitations of conventional microcapsules.