Allometric Scaling of physiologically-relevant organoids

The functional and structural resemblance of organoids to mammalian
organs suggests that they might follow the same allometric scaling
rules. However, despite their remarkable likeness to downscaled organs,
non-luminal organoids are often reported to possess necrotic cores due
to oxygen diffusion limits. To assess their potential as physiologically
relevant in vitro models, we determined the range of organoid masses in
which quarter power scaling as well as a minimum threshold oxygen
concentration is maintained. Using data on brain organoids as a
reference, computational models were developed to estimate oxygen
consumption and diffusion at different stages of growth. The results
show that mature brain (or other non-luminal) organoids generated using
current protocols must lie within a narrow range of masses to maintain
both quarter power scaling and viable cores. However, micro-fluidic
oxygen delivery methods could be designed to widen this range, ensuring
a minimum viable oxygen threshold throughout the constructs and mass
dependent metabolic scaling. The results provide new insights into the
significance of the allometric exponent in systems without a
resource-supplying network and may be used to guide the design of more
predictive and physiologically relevant in vitro models, providing an
effective alternative to animals in research.