Convective dispersion of solutes is inherent to flow in channels because of the nonuniformity of the velocity profile. When diffusion is negligible, for large particles for
Numerous
techniques for mammalian cell culture have been developed
to mimic the complex in vivo three-dimensional structure of tissues
and organs. Among them, the sole use of proteins to create a matrix
where cells are embedded already gives rise to self-organized multicellular
assemblies. Loading cells in a controlled extracellular matrix along
with cell culture and monitoring through a strategy that is compatible
with pipetting tools would be beneficial for high throughput screening
applications or simply for a standardized method. Here, we design
submillimeter compartments having a thin alginate hydrogel shell and
a core made of a collagen matrix where cells are embedded. The process,
using a microfluidic device, is based on a high speed co-extrusion
in air, leading to a compound jet whose fragmentation is controlled.
The resulting core–shell liquid drops are then collected in
a gelling bath that triggers a fast hardening of the shell and is
followed by a slower self-assembly of collagen molecules into fibers.
We show how to formulate the core solution in order to maintain cell
viability at physiological conditions that otherwise induce tropocollagen
molecules to self-assemble, while being able to prevent flow disturbances
that are detrimental for this jetting method. Encapsulated Caco-2
cells, mainly used to model the intestinal barrier, proliferate and
form a closed polarized epithelial cell monolayer where the apical
membrane faces the continuous medium.
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