Biomedical Engineering Reference
In-Depth Information
peptides with reactive functional groups are
in
situ
chemically crosslinked by using multifunc-
tional crosslinkers, enzymes, photopolymeriza-
tion, and gamma irradiation
[124-130]
. Using
these physical or chemical means, a liquid-like
precursor solution can be easily mixed with tar-
get cells, administered into the potential tissue
defect site, and then gelled within several min-
utes to create hydrogel scaffolds. In particular,
ECM-derived polypeptides, including elastin-
based peptides and collagen-like proteins as
well as fibrins and silk proteins have been
widely used to synthesize injectable hydrogel
scaffolds. They show good biocompatibility,
minimal immune responses, and controllable
degradation rates
in vivo
[124-131]
.
casting, phase mixing, and free-form fabrication
methods
[72, 132-134]
. Depending on the pro-
cessing method and the parameters chosen, the
pore size and mechanical integrity of the scaf-
fold can be tailored. Advanced manufacturing
techniques such as free-form fabrication are
particularly attractive in that they offer improved
control over scaffold architecture
[72]
. This
allows for the formation of almost any shape as
well as defined pores and topography.
7.3 SURFACE MODIFICATION OF
SCAFFOLDS
The surface of a tissue engineering scaffold is
important in tissue engineering because it can
directly affect cellular functions such as cell
adhesion, growth, migration, and differentiation
and ultimately the tissue regeneration
[135-137]
.
Although many synthetic polymers have been
used to create 3D scaffolds for directing the
repair and regeneration of damaged tissues,
active control of cell adhesion and downstream
cellular events is still challenging on these scaf-
folds due to the lack of biological recognition
sites that can instruct cells
[136, 138, 139]
. There-
fore, efforts have been made to incorporate bio-
active ECM molecules such as collagen-I, III, IV,
laminin, fibronectin, RGD peptide, etc., and
growth factors onto the surfaces of scaffolds
using various modification techniques, includ-
ing non-covalent and covalent binding
[135, 140]
.
ECM and growth factor molecules can be
non-covalently adsorbed on synthetic scaffolds
by secondary bonding such as electrostatic
interaction and van der Waals forces. Surface-
modified synthetic porous scaffolds such as PCL
and PLGA have the ability to preferentially
differentiate mesenchymal stem cells (MSCs)
into osteogenic cells
[140-142]
. However, non-
covalent adsorption of ECM molecules is a rela-
tively weak force and may, therefore, not be
appropriate for tissue engineering applications
for which prolonged signaling is required.
7.2.3.3 Inorganic Ceramics/Composites
Ceramic materials are central components in
bioscaffolds manufactured for hard-tissue engi-
neering. This is primarily because bone, the pre-
dominant hard mineralized tissue of the human
body, has a large mineral component of a low
crystalline form of the ceramic hydroxyapatite
(HA) (Ca
10
(PO
4
)
6
(OH)
2
). As a result, there have
been attempts to create ceramics and compos-
ites of ceramics that elicit the same biological
response and have the same physical properties
of the native inorganic matter. Some absorbable
ceramic materials that have been investigated
for bone tissue engineering include CaCO
3
(argonite), CaSO
4
-2H
2
O (Plaster of Paris), and
Ca
3
(PO
4
)
2
(beta-whitlockite, a form of tri-calcium
phosphate, and TCP)
[70]
. The most commonly
studied CaP ceramics, however, are TCP, HA,
and tetracalcium phosphate. Calcium-phos-
phorous scaffolds are advantageous because
they are biocompatible, elicit a minimal immu-
nologic response, and can be processed to
avoid systemic toxicity
[71]
. They are also oste-
oconductive and integrate well with natural
bone
[71]
.
To make 3D porous ceramic scaffolds, a vari-
ety of techniques may be employed. These meth-
ods include the gas-foaming method, template
