The secretion rate of albumin is a key indicator of function
in
liver tissue models used for hepatotoxicity and pharmacokinetic testing.
However, it is not generally clear how to determine molecular secretion
rates from measurements of the molecular concentration in supernatant
media. Here, we develop computational and analytical models of molecular
transport in an experimental system that enable determination of albumin
secretion rates based on measurements of albumin concentration in
supernatant media. The experimental system is a 3D-bioprinted human
liver tissue construct embedded in a 3D culture environment made from
packed microgel particles swollen in liquid growth media. The mathematical
models reveal that the range of albumin synthesis rates necessary
to match experimentally measured albumin concentrations corresponds
to reaction-limited conditions, where a steady state of albumin spatial
distribution is rapidly reached between media exchanges. Our results
show that temporally resolved synthesis rates can be inferred from
serial concentration measurements of collected supernatant media.
This link is critical to confidently assessing in vitro tissue performance in applications where critical quality attributes
must be quantified, like in drug development and screening.