Biomedical Engineering Reference
In-Depth Information
preferential adhesion to the surface has been one of the major endeavors for tissue
engineers over the last decade. Chemical and physical cues are the two most widely
studied modifi cations that are made to the surface of a material. One of the most
diffi cult tasks is determining the role played by each of these treatments and fi nding
the proper balance between them for optimal cell attachment and growth. Physical
cues, artifi cially created on the surface of a material, alone have been shown to sig-
nifi cantly affect organization of cells in culture through the phenomenon of contact
guidance (Hanarp et al.
1999
). This has been demonstrated in both two-dimensional
and three-dimensional cultures with artifi cial tissues being created that are strik-
ingly similar in both appearance and function to natural tissues (Deutsch et al.
2000
;
Norman and Desai
2005
). The key to recapitulating tissue organization and function
in vitro may lie in the ability to recreate the cells' ECM environment.
The ECM has considerable topographic detail at the nanometer scale. It has been
very well established that micrometer-size features on a culture surface can affect
parameters such as migration, adhesion and morphology independent of biochemi-
cal cues presented to the cells (Rahul Singhvi
1994
). Further evidence of topo-
graphic control of cellular growth, independent of biochemical modulation, was
shown by growing bovine aortic endothelial cells on polymer casts of the suben-
dothelial ECM (Goodman et al.
1996
). Polyurethane casts of the subendothelial
ECM of arteries and veins showed fi delity of feature replication down to 50 nm.
After several days of culture on the cast, cells appeared more similar to those in
native arteries than cells cultured on untextured surfaces. Obviously, the nanometer-
size features of the ECM alone can go a far way to recreating in vivo cellular
characteristics.
As tissue engineers, all size scales of a scaffold must be considered when engi-
neering an artifi cial tissue: the superstructure, the overall shape of the scaffold; the
microstructure, the cellular-level structure of the surface; and the nanostructure, the
subcellular-level structure of the surface. The fi rst two levels of this hierarchy have
been very well studied over the years and methods for controlling them are well
established. The nanoscale structure and its infl uence on cells, however, is less well
understood, yet just as important as the levels above it. When cells are cultured
outside the body on a polymeric scaffold, or any one of a variety of materials used
as substrates for a biomedical device or implant, often, only the macro- and
microscale features are considered. However, the nanoscale features of all of these
materials may greatly affect, for better or worse, the culture in question. The inher-
ent nanotopography encountered by the cells on such materials is most likely differ-
ent from that found in their native environment and may provide physical cues that
lead to less than desirable growth and function.
Understanding the architectural make-up of the ECM and how it infl uences the
cells in contact with it will allow scientists and engineers to design materials that
mimic what the cells “see” when they explore their native environment. Researchers
are now looking to see if and how domains of nanometer-size variations in topogra-
phy of the ECM affect the cells growing on them. Investigative studies into the nano-
scale topography of basement membranes from different species (including human)
