Biomedical Engineering Reference
In-Depth Information
extracellular matrix and with each other. (3) The tissue cell monolayers on coated
2-D surface, such as poly-L-lysine, collagen gels, fi bronectin, laminin, and Matrigel
( Kleinman et al. 1986 ; Kleinman and Martin 2005 ) as well as other synthetic mate-
rials containing segments of adhesion motifs, have only part of the cell surface
attached to the materials and interact with neighboring cells. The remaining parts
are often directly exposed to the culture media, unlike the majority of tissue envi-
ronment where every cell intimately interacts with its neighbor cells and extracel-
lular matrix; of course, there are exceptions to such general statement, e.g., airway
epithelial cells. Thus 3-D-matrix interactions display enhanced cell biological activ-
ities. (4) The transport phenomena of 2-D and 3-D are drastically different. In 2-D
culture systems, cytokines, chemokines and growth factors quickly diffuse in the
media across the culture dish. This is again in sharp contrast to the in vivo environ-
ment where chemical and biological gradient diffusion systems play a vital role in
signal transduction, cell-cell communications and development. (5) Cells cultured
on a 2-D Petri dish are not readily transportable, that is, it is nearly impossible to
move cells from one environment to another without incurring changes in the cell-
material and cell-cell interactions. For example, cell collections using trypsiniza-
tion or mechanically using cell scrapers may have adverse effect on cell-materials/
environment interactions. In contrast, cells cultured on 3-D scaffolds are more read-
ily transportable without signifi cantly harming cell-material and cell-cell interac-
tions, thus providing a signifi cantly new way to study cell biology.
Micro- and Nanoscales: Why Are They Important?
The importance of length scales is apparent, for example, when considering the
scales of trees and grasses (Fig. 1 ). Both are made of the same basic building blocks;
sugars that are polymerized by enzymes to produce cellulose fi bers. Trees, usually
20-40 cm in diameter, are common in forests. If animals are in the forest, they can
either go between the trees or climb onto the trees, they cannot go cross through the
trees because animals are similar in scales as the trees. On the other hand, grasses
are usually 0.5 cm (commonly 0.3-1 cm in diameter) in diameter. Animals can be
fully embedded in and surrounded by high grass, yet can move freely within the
high grass fi eld. Perhaps, this analogy can be extended to scaffolds of various scales
for cells. Cells are commonly micrometer-scales, 5-20 mm, objects. When cells are
residing on microfi ber polymers, they are about same scales as the microfi bers.
When the cells are in the extracellular matrix, they are embedded within the nanofi -
ber matrix, which they exceed in size by a factor of ~1,000.
In the last three decades, several biopolymers, including poly-L -lactide acid
(PLLA), poly-lactic-co-glycolic acid (PLGA), PLLA-PLGA copolymers and other
biomaterials including alginate, agarose, collagen gels and others, have been devel-
oped to culture cells in 3-D (Ratner et al. 1996 ; Lanza et al. 2000 ; Yannas 2001 ;
Atala and Lanza 2002 ; Hoffman 2002 ; Palsson et al. 2003 ) . These culture systems
have signifi cantly advanced our understanding of cell-material interactions and
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