Biomedical Engineering Reference
In-Depth Information
and different tissues have shown varied and rich nanoscale topography with features
ranging from only a few to hundreds of nanometers (Yamasaki et al.
1990
; Shirato
et al.
1991
; Kubosawa and Kondo
1994
; Abrams et al.
2000a,
b,
2002,
2003
) .
A variety of methods have been used to study tissue samples including atomic
force microscopy (AFM), transmission electron microscopy (TEM) and scanning
electron microscopy (SEM). The basement membranes were found to be a composed
of a complex arrangement of fi bers and pores that result in a landscape rich in three-
dimensional features. These features match the size scale of a cell's processes that
explore its environment and the adhesion sites it makes with the ECM. Modeling of
the surface of the macaque corneal epithelium basement membrane preformed by
Abrams et al. shows an amplifi cation of surface area for cell interactions of 400%
over fl at culture surfaces (Abrams et al.
2000a
). This large increase in surface area
for cell-matrix interactions to take place could have a large infl uence on the abilities
of cells to attach and migrate to the surface of the ECM.
The use of AFM has allowed for the quantifi cation of feature height, frequency and
overall roughness of the basement membrane. This is important because many micro
and nanofabrication techniques are designed to create features of specifi ed height and
frequency. With many techniques it is now possible to recreate the cells natural envi-
ronment at a scale equivalent to that which an individual cell would experience. For
example, chemical etching of materials to control the nanoscale roughness of a sur-
face is a technique that is being widely investigated for studying nanotopography and
its effects on cellular behavior. These studies have led to the engineering of surfaces
for in vitro culture that display the same type of nanoscale topography to cells as
found in vivo (Fan et al.
2002
; Thapa et al.
2003
; Pattison et al.
2005
) .
What type of topographical features to create and the technique used to create
them will depend on the tissue type and what aspect of cellular growth needs to be
modulated. Determining the appropriate factors will involve a detailed study of the
physical environment of the tissue in question as well as creating model surfaces to
study the effects on living cells. The types of nanotopographical features that can be
created on materials fall into two main categories: unordered topographies and
ordered topographies. Unordered topographies are typically those which spontane-
ously occur during processing. Examples of such topographies can be made using
techniques such as polymer demixing, colloidal lithography and chemical etching.
Surfaces patterned in this manner tend to give features that are random in orienta-
tion and organization with imprecise or no control over feature geometry. These
techniques, however, are usually simpler, quicker and less costly than the more
complex equipment and processes needed to create ordered topographies. Ordered
topographies are those which can be created with techniques like photolithography
and electron beam lithography. These methods allow the creation of prescribed pat-
terns that are well ordered and geometrically precise. However, they usually require
very expensive equipment and a high level of expertise. The value of an ordered
topography over an unordered topography was investigated by Curtis et al. (
2001
) .
In their experiment, surfaces of various nanoscale ordered patterns were created
using electron beam lithography, and surfaces with nanoscale unordered patterns
were created using colloidal lithography. Rat epitonon fi broblasts showed higher
