A chip-based platform for the in vitro generation of tissues in three-dimensional organization.
We describe a multi-purpose platform for the three-dimensional cultivation of tissues. The device is composed of polymer chips featuring a microstructured area of 1-2 cm(2). The chip is constructed either as a grid of micro-containers measuring 120-300 x 300 x 300 microm (h x l x w), or as an array of round recesses (300 microm diameter, 300 microm deep). The micro-containers may be separately equipped with addressable 3D-micro-electrodes, which allow for electrical stimulation of excitable cells and on-site measurements of electrochemically accessible parameters. The system is applicable for the cultivation of high cell densities of up to 8 x 10(6) cells and, because of the rectangular grid layout, allows the automated microscopical analysis of cultivated cells. More than 1000 micro-containers enable the parallel analysis of different parameters under superfusion/perfusion conditions. Using different polymer chips in combination with various types of bioreactors we demonstrated the principal suitability of the chip-based bioreactor for tissue culture applications. Primary and established cell lines have been successfully cultivated and analysed for functional properties. When cells were cultured in non-perfused chips, over time a considerable degree of apoptosis could be observed indicating the need for an active perfusion. The system presented here has also been applied for the differentiation analysis of pluripotent embryonic stem cells and may be suitable for the analysis of the stem cell niche.
Gottwald
Eric
E
Institute for Biological Interfaces, Forschungszentrum Karlsruhe, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany. eric.gottwald@ibg.fzk.de
Giselbrecht
Stefan
S
Augspurger
Caroline
C
Lahni
Brigitte
B
Dambrowsky
Nina
N
Truckenmüller
Roman
R
Piotter
Volker
V
Gietzelt
Thomas
T
Wendt
Oliver
O
Pfleging
Wilhelm
W
Welle
Alex
A
Rolletschek
Alexandra
A
Wobus
Anna M
AM
Weibezahn
Karl-Friedrich
KF
D000818:Animals; D019149:Bioreactors; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D004563:Electrochemistry; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000502:physiology / Q000648:ultrastructure; D004867:Equipment Design; D044085:Microfluidics / Q000295:instrumentation / Q000379:methods*; D008855:Microscopy, Electron, Scanning; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000502:physiology / Q000648:ultrastructure; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D023822:Tissue Engineering
D011108:Polymers