4

Notes

1. It is recommended to autoclave the bioreactor vessels as close

as possible to the time they will be used to ensure sterility is

maintained.

2. The arms of the Alvetex® insert line up with slots in the PTFE

holder to ensure a stable fit with no rotation. When the insert is

correctly positioned it should sit flat with minimal movement

possible.

3. Growth of HepG2 models for greater time points can be

carried out, with a further week of culture possible without

further media changes. For longer periods than this the quan-

tity of cells can lead to deleterious effects of the large tissue

mass such as the formation of a necrotic core.

4. If samples are not going to be imaged immediately, they can be

stored for several weeks in the dark at 4 C. For optimum

results, it is recommended to image the samples as soon as

possible.

References

1. Jensen C, Teng Y (2020) Is it time to start

transitioning from 2D to 3D cell culture? Front

Mol Biosci 7:1–15

2. Hansmann

J, Egger

D, Kasper C (2018)

Advanced dynamic cell and tissue culture. Bio-

engineering 5(3):5–7

3. Knight E, Przyborski S (2015) Advances in 3D

cell culture technologies enabling tissue-like

structures to be created in vitro. J Anat 227

(6):746–756

4. Sonbol HS (2018) Extracellular matrix remodel-

ing in human disease. J Microsc Ultrastruct 6

(3):123–128

5. Nicolas J, Magli S, Rabbachin L, Sampaolesi S,

Nicotra F, Russo L (2020) 3D Extracellular

matrix mimics: fundamental concepts and role

of materials chemistry to influence stem cell fate.

Biomacromolecules 21(6):1968–1994

6. Ballermann BJ, Dardik A, Eng E, Liu A (1998)

Shear stress and the endothelium. Kidney Int

Suppl 54(67):100–108

7. Verkman AS, Dix JA (1984) Effect of unstirred

layers on binding and reaction kinetics at a mem-

brane surface. Anal Biochem 142(1):109–116

8. Darling NJ, Mobbs CL, Gonza´lez-Hau AL,

Freer M, Przyborski S (2020) Bioengineering

novel in vitro co-culture models that represent

the human intestinal mucosa with improved

Caco-2 structure and barrier function. Front

Bioeng Biotechnol 8:1–15

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Henry W. Hoyle et al.