Page 62 - Academic Press Encyclopedia of Physical Science and Technology 3rd BioTechnology

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Encyclopedia of Physical Science and Technology EN002J-63 May 18, 2001 14:16

Biomineralization and Biomimetic Materials 203

toughening alumina ceramic by entrained aluminum metal cal loads will limit the lifetime of most implants to about
particles. 10 years. In addition, biocompatibility is not a material
property but is very dependent on the specific environ-
E. Biomimetic Processing Methods ment of the implant, in terms of implant site in the body,
animal species, and animal age. Strategies to eliminate
Freeform fabrication methods allow objects to be built
these problems include the use of biodegradable materi-
as a series of layers directly from a three-dimensional
als, which will eventually be replaced by natural tissue,
computer representation. These allow only one material
and tissue engineered implants, where as much of the de-
to be used at a time, or a material plus a soluble support
vice as possible is formed from tissue grown in vitro on a
structure. It is clearly feasible to combine several differ-
synthetic support before implantation.
ent materials into a single object, which would allow the
Tissue engineering imposes a need to understand the in-
building of something much closer to an organism. A re-
teractions between neighboring cells, between cells, and
port on simple robots, which were allowed to evolve in a
between cells and synthetic surfaces. Cell binding to a
virtual environment and then were built by freeform fabri-
biological surface proceeds through a series of stages in-
cation, shows how evolutionary methods might be applied
cluding physical adsorption, interaction between surface
to manufactured objects.
macromolecules and specific binding sites on the surface,
To build a crude organism would require resolution at
reorganization of the macromolecules in the cell mem-
the scale of about 10 µm. Most current freeforming meth-
brane to bring more binding sites into contact with the
ods allow resolution down to about 100 µm and a limited
surface, and then specific changes in the cell induced by
materials set. Microcontact printing and related methods
the surface.
allow much higher resolution, down to about 1 µm, but ef-
At the physical adsorption level, studies of cell attach-
fectively are restricted to one layer. There is much current
ment to self-assembled monolayers on silicon or glass
interest in ink-jet printing methods, which could provide
have shown that attached polyethyleneoxide chains form
the required 10-µm resolution while allowing many layers
a structureless hydrophilic barrier layer and will prevent
to be deposited.
adsorption. Different polar end groups will allow cells
In both synthetic and biological structures, it is useful
to absorb, and printed surface patterns with binding and
to keep in mind a distinction between design and pattern-
nonbinding areas can be used to control cell shape.
ing.Phaseseparation,crystallization,andaggregationpro-
Cells recognize and bind to simple short sequences of
cesses can give rise to patterns in two and three dimensions
amino acids in a protein exposed on a surface. RGD
on a scale from millimeters to nanometers which reflect
(arginine–glycine–aspartic acid) and RADS (arginine–
the kinetics of the separation and diffusion processes. To
alanine–aspartic acid–serine) are sequences that can be
form working devices or organisms, we need to build to
used to induce strong cell attachment. Thus, suitable poly-
a nonrecurring design, which may include patterned ele-
mers can be produced which will promote formation of
ments. If we seek to adopt biomimetic processes, we will
particular cell types to the surfaces for tissue engineering.
need to exploit self-assembling structures and patterns but
In the case of bone implants, there has been much in-
within an overall design.
terest in the use of bone morphogenic proteins, now pro-
In current silicon technology, photolithographic meth-
duced from cloned bacteria. One group of a family of
ods can form two-dimensional designs down to less than
cell-signaling proteins are known to induce the develop-
1 µm. Much finer resolutions are achievable in labora-
ment of bone or other tissues when locally released in
tory methods. Three-dimensional designs can be formed
the body. A similar set of signals induces growth of small
to below 1 µm using two-photon methods but commer-
blood vessels and is an important factor in the develop-
cial freeforming methods are limited to about 100 µm. In
ment of many cancers. By allowing implants to release
biology, there are many examples of patterns forming at
such signaling proteins, it should be possible to speed the
the nanometer level but most designs are on the scale of
integration of the implant; however, much remains to be
individual cells, a few tens of microns. There are struc-
learnted about the appropriate concentrations, gradients,
tures, such as sensing hairs, which are much finer but the
and timing of these signals. All of these efforts take us in
spacing between them is still on the 10-µm scale.
the direction of making synthetic organs that look more
like a natural organ transplanted from an identical twin.
F. Cell Adhesion and Tissue Engineering
Belcher and co-workers have recently demonstrated
9
Biomedical engineering is becoming more concerned with that a phage library, displaying 10 different peptide se-
the problems of the long-term biocompatibility of syn- quences at the surface, can be used to identify short pep-
thetic implants. Material wear and degradation and tissue tide sequences that selectively bind to inorganic semicon-
loss or chronic inflammation due to changing mechani- ductor surfaces. Sarikaya and co-workers have developed