Biomaterials for MEMS

Hydrogel-Based Microfluidic Cell Culture 91

testing to give predictive data during further in vivo testing, the cells in culture

must mimic as closely as possible the in vivo behavior. Thus, drugs developed

using a monolayer screening system may not have the same activity against solid

tumors.

10

Currently, several three-dimensional cell culture systems are already used

in tumor and normal cell research.

9

Multicellular spheroids, in which spherical

aggregates are grown in suspension, are used to investigate tumor cell metabolism.

Cellular multilayers, in which layers of cells are cultured on porous membranes,

are used in studies of drug transport. Established 3-D culture methods used to

study drug penetration in tumors include multicellular spheroids, which are cell

aggregates typically suspended in rotating flasks, or spinner culture.

11

In collagen

cultures, a solid tumor specimen is embedded in a rat tail collagen gel, in order

to maintain the three dimensional structure. Multilayered cell cultures (MCCs)

feature thick layers of cells grown on permeable support membranes.

12

In one

configuration, the MCC separates two reservoirs which contain stirred media; the

drug is added to one reservoir and drug penetration through the thick (∼ 200 μm)

layer of cells is measured by sampling from the second reservoir.

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5.1.3 Microscale Cell Culture Using Hydrogels

Current trends aim to culture cells in a mic roscale three-dimensional environment

that more closely mimics the natural extracellular environment.

15

Miniaturization

and spatial control are two goals addressed in microfluidic cell culture systems.

First, miniaturization permits more precise control of the microenvironment,

such as gradients in soluble factors. Gradients in biomolecules are essential —

they guide cell growth, migration, and differentiation.

16

In Petri dishes, secreted

molecules are quickly dispersed over the entire bulk volume, and this loss of

Figure 5.1. A cell in a three-dimensional culture forming links with the scaffold.

2

For color

reference, see page 260.

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