Biomedical Engineering Reference
In-Depth Information
Covalently conjugated bioactive molecules
have been shown to be stable under physiologi-
cal conditions and maintain biological activity
after prolonged implantation in the localized
microenvironment. For covalent binding, sur-
faces of preformed scaffolds are converted into
reactive functional groups such as OH, COOH,
and NH
2
. These functional groups can undergo
further reactions with ECM proteins, peptides,
and growth factors on the surfaces of various
synthetic scaffolds, including PLLA, PLGA, and
PCL. These surface-modified scaffolds have
significantly enhanced biological performance
after covalent modifications
[143-146]
. Surface
modification can be performed after a porous
scaffold has been fabricated. It therefore does
not usually affect the scaffold structure and
mechanical properties significantly. However,
density and distribution of the bioactive mole-
cules on the scaffold surface should be opti-
mized for appropriate control of cell behavior
[143, 147]
.
have been shown to be effective in retaining the
bioactivities of various therapeutic agents
[148-151]
. There also have been attempts to
modify a scaffold with biological factors using
the layer-by-layer process
[152]
. A multilayered
heparin-based polyelectrolyte delivery system
is constructed on the surface of a PLGA layer
that facilitates the loading of basic fibroblast
growth factor (bFGF) and increases growth fac-
tor stability. When growth factor molecules are
released in a sustained manner and not instan-
taneously, greater cell proliferation was
observed
in vitro
. Biological factors have been
incorporated in porous scaffolds for a sustained
release system by adding them into a polymer
solution or emulsion and further processing
the polymer solution
[153, 154]
. The gas-foaming
process has been shown to entrap PLGA micro-
spheres containing biomolecules in a porous
scaffold for sustained delivery at a tissue defect
site
[155]
. This technique allows for the release
of single or multiple biological factors in a spa-
tially and temporally controlled manner.
7.4 BIOACTIVE MOLECULE
D
ELIVERY WITH SCAFFOLD
S
7.5 CONCLUSIONS AND
PERSPECTIVES
In addition to a scaffold's microstructural, topo-
graphical, and other physical properties, bio-
logical signaling is also a key component for cell
function and tissue regeneration. Endogenous
signaling molecules such as growth factors are
often not sufficient for the repair of large size
defects, necessitating the addition of exogenous
signaling molecules. These biomolecules usu-
ally have short half-lives, and their concentra-
tion gradients play a prominent role in cellular
responses. For effective tissue regeneration, the
delivery system must be sustained and should
overcome the short half-life of these bio-
molecules
in vivo
.
Several promising approaches are available
to couple growth factors to the biomaterial sur-
face so they are readily bioavailable. Controlled
release systems using micro- and nanospheres
In reviewing various approaches for the
design and engineering of 3D scaffolds that
closely approximate human tissue ECM, it is
clear that the scaffold's geometry, topography,
porosity, density, and other physicochemical
properties regulate many cellular processes.
New materials and combinations of materials,
as well as improved scaffold designs based on
novel processing techniques, are continuously
advancing the tissue engineering field, par-
ticularly in recent years. However, the biologi-
cal performance of scaffolds for specific
applications
in vitro
and
in vivo
is not fully
understood. When the biological performance
of scaffolds is clear to researchers, a rationale
for the design of multifunctional scaffolds can
be implemented.
