Biomedical Engineering Reference
In-Depth Information
material tends to produce a porous block with brittle and
fragile structure. This drawback may be overcome by
formation of composites from b-TCP and flexible poly-
mers, which must be osteoconductive if portion of
b-TCP is present on the surface of scaffold.
perform other specific functions is a coordinated re-
sponse to the molecular interactions with ECM effec-
tors. This flow of information between cells and their
ECM is bidirectional.
In multicellular organisms contacts of cells with
neighboring cells and the surrounding ECM are mediated
by cell adhesion receptors. Among them the integrin
family comprises the most numerous and versatile groups.
They are a large family of heterodimeric, cell surface
molecules, and are the most prominent ECM adhesion
receptors of animal cells for many of the ECM adhesion
molecules. They play not only a major role in linking the
macromolecules of the ECMwith the cell's cytoskeleton,
cell-cell adhesion, and binding to proteases, but are also
important in processes like embryogenesis, cell differ-
entiation, immune response, wound healing, and hemo-
stasis. Integrins consist of two non-covalently associated
transmembrane subunits, termed a and b. To date 18a
and 8b subunits are known, which form 24 different
heterodimers. The combination of particular a and
b subunits determines the ligand specificity of the
integrin. Some integrins, however, are highly pro-
miscuous, e.g., the avb3 integrin binds to vitronectin,
FN, von Willebrand factor, osteopontin (OP), tenascin,
bone sialoprotein, and thrombospondin. Vice versa,
ECM molecules like FN are ligands for several integrins.
Fibronectin is a disulfide-linked dimeric glycoprotein
prominent in many ECMs and present at about 300
m
g/ml in plasma. It interacts with collagen, heparin, fibrin,
and cell surface receptors of the integrin family. In 1984,
the tripeptide motif RGD (
Fig. 7.2-15
)
[11]
was iden-
tified by Pierschbacher and Rouslahti as a minimal es-
sential cell adhesion peptide sequence in FN. The RGD
peptides inhibit cell adhesion to FN on the one hand, and
promote cell adhesion when they are immobilized on
surfaces on the other hand. Since then, cell-adhesive
RGD sites were identified in many other ECM proteins,
including vitronectin, fibrinogen, von Willebrand factor,
collagen, LN, OP, tenascin, and bone sialoprotein as well
as in membrane proteins, in viral and bacterial proteins,
7.2.4.5 Composite scaffolds
Ceramics including dense and porous HAp, TCP ce-
ramics, bioactive glasses, and glass-ceramics have been
combined with a number of polymers including collagen,
chitosan, and poly(a-hydroxyacid)s. The combination of
such polymers with a bioactive component takes advan-
tage of the osteoconducting properties (bioactivity) of
HAp and bioactive glasses and of their strengthening
effect on polymer matrices. The composite is expected
to have superior mechanical properties than the neat
(unreinforced) polymer and to improve structural in-
tegrity and flexibility over brittle glasses and ceramics
for eventual load-bearing applications. Composite fab-
rication research has focused on developing polymer/
ceramics blends, precipitating ceramic onto polymer tem-
plates, coating polymers onto ceramics, or ceramics onto
polymers. Polymer processing techniques including com-
bined solvent-casting and salt-leaching, phase separation
and freeze drying, and immersion-precipitation have
been used for the preparation of highly porous PLA/HAp
scaffolds.
In situ
apatite formation can also be induced by
a biomimetic process in which polymer foams are in-
cubated in a simulated body fluid.
7.2.5 Surface modifications
Both bulk (e.g., strength and degradability) and surface
properties of biomaterials are important in tissue engi-
neering. Generally, bulk and surface properties are
interwound. Often, materials are chosen for their favor-
able bulk properties, and their unfavorable biological in-
teractions are improved by surface modifications. The
success of tissue engineering depends on interactions at
the cell-scaffold interface, including the cell adhesion
and proliferation, expression and activity of regulatory
signaling molecules, and biomechanical stimuli.
Sidechain guanidino
group
Sidechain carboxyl
group
HN
NH
2
7.2.5.1 Cell interactions in natural tissues
HN
OH
A highly dynamic and complex array of biophysical and
biochemical signals are transmitted from the outside of
a cell by various cell surface receptors and integrated by
intracellular signaling pathways. The signals converge to
regulate gene expression and ultimately establish cell
phenotype. This indicates that the ultimate decision of
a cell to differentiate, proliferate, migrate, apoptose, or
O
O
N
C
-(carboxyl)
terminus
N
-(amino)
terminus
OH
H
H
2
N
O
O
Arginine
R
Glycine
G
Aspartate
D
Fig. 7.2-15 The molecular formula and nomenclature of RGD.
