Abstract
Owing to species-specific differences in liver pathways, in vitro human liver models
are utilized for elucidating mechanisms underlying disease pathogenesis, drug development,
and regenerative medicine. To mitigate limitations with de-differentiated cultures,
bioengineers have developed advanced techniques/platforms, including micropatterned
cocultures, spheroids/organoids, bioprinting, and microfluidic devices, for perfusing
cell cultures and liver slices. Such techniques improve mature functions and culture
lifetime of primary and stem-cell human liver cells. Furthermore, bioengineered liver
models display several features of liver diseases including infections with pathogens
(e.g., malaria, hepatitis C/B viruses, Zika, dengue, yellow fever), alcoholic/nonalcoholic
fatty liver disease, and cancer. Here, we discuss features of bioengineered human
liver models, their uses for modeling aforementioned diseases, and how such models
are being augmented/adapted for fabricating implantable human liver tissues for clinical
therapy. Ultimately, continued advances in bioengineered human liver models have the
potential to aid the development of novel, safe, and efficacious therapies for liver
disease.
Keywords
tissue engineering - drug development - micropatterned cocultures - organoids
