Biomedical Engineering Reference
In-Depth Information
cellular efforts to achieve a biomechanical equlibrium
condition with a resulting minimal net sum of forces. The
signficance of this theory has been described extensively
by
Ingber (1993, 1994)
in his tensegrity models.
According to this model, the anisotropic geometry of
substratum surface features establishes stress- and shear-
free planes that influence the direction of cytokeletal el-
ements in order to create a force economic situation
(
Oakley and Brunette, 1993, 1995; O'Neill
et al.
, 1990
).
transduced to the cytoskeleton via cell contact sites and
cell surface receptors. In this model, the cytoskeleton is
considered as a static structure. This is incorrect. The
cytoskeleton is a highly dynamic system (
Lackie, 1986
),
which is constantly broken down and elongated in living
cells. Consequently, if the mechanical theory is still true,
the fundamentals should be derived from other pro-
cesses than just the remodeling of the cytoskeleton
(
Walboomers
et al.
, 1998a
). Studies on cell nuclear
connections to the cytoskeleton may offer insights into
the relationships between surface features and cell be-
havior (Maniotis
et al.
, 1997).
Apart from changes in cell size, shape, and orientation,
surface microtopography has been reported to influence
other cell processes. For example, several studies de-
scribed changes in cellular differentiation, DNA/RNA
transcription, cellular metabolism, and cellular protein
production of cells cultured on microtextured surfaces
(
Chou
et al.
, 1995; Hong and Brunette 1987; Matsuzaka
et al.
, 1999
; von Recum and van Kooten, 1995; Singhvi
et al.
, 1994;
W´jciak-Stothard
et al.
, 1995
). A study using
m
CP surfaces with square cell adhesive and nonadhesive
domains has shown that where surface adhesive domains
are small (
<
75
m
m), apoptosis levels in endothelial cells
is high (particularly so for 5
m
m
5
m
m domains) and
when cells are placed on larger domains, cell spreading
and growth occurs (
Chen
et al.
, 1997
). Whether these
additional effects have to be considered as independent
phenomena is still a topic of discussion. According to
Hong and Brunette (1987)
, the good news was that
surface microtopography can enhance the production of
specific, perhaps favorable proteins. On the other hand,
the production or secretion of less favorable metabolic
products can also be enhanced. If this occurs, this might
have a deleterious effect on the overall cell response. For
example, a rise in the production or release of proteinases
may not be beneficial for connective tissue cell response.
This example shows that, at least at the molecular level,
the regulation of cell function
The
in vitro
effect of surface
microtexturing
A considerable number of
in vitro
studies have been
performed to determine which of the hypotheses men-
tioned in the preceding section can be experimentally
supported. Up to this point, we have to emphasize that
comparison of the obtained data is difficult because most
of the studies had differences in the surface textures of the
materials explored. In addition, different bulk materials
were also applied. Modern surface feature fabrication
methods have allowed more precise surfaces to be fabri-
cated so studies from different groups might be compared.
In the experiments performed by Curtis
et al.
(
Clark
et al.
, 1987
, 1990, 1991;
Curtis and Wilkinson, 1997
)
with fibroblasts and macrophages cultured on micro-
grooved glass substrates, groove depth was observed to be
more important than groove width in the establishment
of contact guidance. Therefore, these experiments be-
lieve that cytoskeletal flexibility and the possibility of
making cellular protrusions are the determining cellular
characteristics for contact guidance. As a consequence of
these studies, other reseachers further explored the in-
volvement of cytoskeletal elements in cell orientation
processes. Also, the possibility of a relationship between
cytoskeletal organization and cell-substrate contact sites
was investigated (den Braber
et al.
, 1995, 1996, 1998b;
Meyle
et al.,
1991, 1993; Oakley and Brunette, 1993,
1995; Oakley
et al.
, 1997; Walboomers
et al.
, 1998a,
1999). Although these studies varied in cell type used,
substrate surface feature dimensions and substrate bulk
chemical composition, the results clearly confirmed that
very fine microgrooves (
2
m
m) have an orientational
effect on both cell body and cytoskeletal elements.
Transmission electron microscopy observations showed
that cells were only able to penetrate into very shallow
(
1
m
m) or wide (
5
m
m) microgrooves. Cells were also
observed to possess cell adhesion structures that were
wrapped around the edge of a ridge or attached to the
wall of the ridge. On the basis of these findings, these
investigators suggested that the mechanical properties of
cellular structures can never be the only determining
factor in contact guidance.
Further, a mechanical model to explain contact guid-
ance suggests that the ''surface feature stimulus'' is
by substrate
surface
microtexture may be a complex affair.
The
in vivo
effect of surface
microtexturing
Based upon interesting results from
in vitro
experiments,
in vivo
studies with microtextured implants have been
performed. Unfortunately, the results from the various
studies are not consistent. For example, in some animal
experiments it was demonstrated that silicone-coated fil-
ters and bulk SR implants provided with surface features
of 1-3
m
m showed a minimal inflammatory response with
direct fibroblast attachment and a very reduced connective
capsule (
Campbell and von Recum, 1989; Schmidt and
von Recum, 1991, 1992
). In contrast, other animal studies
