Biomedical Engineering Reference
In-Depth Information
interactions that ultimately lead to improved
biocompatibility, as these interactions propagate
through the chain of cause and effect outlined in
Williams' Four Components of Biocompatibility,
diagrammed in
Figure 8.3
.
Using
Figure 8.4
as a guide, we can surmise
that the size scale of the pattern relative to the
size of interacting constituents will be very
important. If the size of the pattern is large
compared to the scale of these constituents, then
it seems likely that the net effect will be more
like a weighted average of biological responses
to pure, macroscopic-pattern constituents. This
seems to be evident in cell responses to surfaces.
Cell shape and phenotypic response seem most
pronounced when the scale of the surface feature
is some fraction of cell size
[90, 99-101]
. The
effects of patterning at the size scale of proteins
are much less clear. Not only are nanoscale
patterns technically challenging to make and
characterize
[93]
, but also understanding this
surface interaction phase of the biological
response remains well outside the grasp of
modern biomaterial surface science.
As pattern size decreases, the relative contri-
bution of edges between domains necessarily
increases. The transition in chemistry between
edges seems likely to be important in the orien-
tation of proteins that differentially adsorb to
surfaces with different surface chemistry/
energy
[102]
. If molecular simulations are a
guide, it can also be expected that the structure
and reactivity of water at molecular edges will
be quite different than within bulk solution
[103]
. It seems reasonable to speculate that mac-
roscopic biological responses to nano-patterned
surfaces such as blood plasma coagulation, men-
tioned in the preceding section, might be traced
to such difficult-to-characterize phenomena.
what nature does through a purely synthetic
strategy. Examples include engineering super-
hydrophobic properties of lotus leaves onto sur-
faces
[104-110]
and immobilizing biological
molecules with specific directed function, or
even immobilizing living cells
[111-113]
. Biomi-
metic molecules include glycoproteins, peptides,
phospholipids and proteins (enzymes), and sac-
charides. Many different strategies can be
employed to achieve biomimicry, including non-
specific adsorption of macromolecules and cova-
lent bonding to a surface, frequently using
chemical grafting reactions
[114-116]
or through
application of plasma technology, briefly men-
tioned in Section
8.3.2.1
[116-118]
. Many appli-
cations of biomimetic surfaces are not explicitly
designed for improved biocompatibility of bio-
materials, as defined in Section
8.1.2
, but a level
of compatibility with biology in general is
required to retain biological activity.
8.3.4.1 Biomimetic Biomaterials
As applied to biomaterials, biomimetic surfaces
are intended to guide the biological response
by recruiting proteins and cells, typically to
influence integration and healing of implants.
In those cases when the activity of a particular
biological molecule is known to direct a particu-
lar desirable biological response, these specific
molecules can be immobilized on a surface. An
example is immobilization of bone morpho-
genic protein (BMP) onto orthopedic and dental
implant materials to induce bone in-growth and
healing of the implant into surrounding bone.
BMPs constitute a family of growth factors that
induce formation of bone and cartilage. There
are many similar biological macromolecules that
are known to exhibit specific stimulatory effects.
An alternative to immobilizing biologically
active molecules onto a surface is to create a
surface that specifically recognizes and binds
selected proteins from the biological milieu into
which the biomimetic biomaterial is placed
[117, 119, 120]
. Here chemical or plasma-based
reactions are used to template a nanocavity with
8.3.4 Biomimetic Surface Engineering
Biomimetic surfaces take design cues from the
biophysical and/or biochemical properties
observed in nature in an attempt to accomplish
