Biomedical Engineering Reference
In-Depth Information
cartilage repair and other tissue-engineering
applications.
A new class of thermogelling poly
(organophosphazines) containing oligomeric
side chains of hydrophilic methoxypoly
(ethylene glycol) (MPEG) and hydrophobic tri-
peptide or tetrapeptide side groups shows
promise for drug delivery and tissue engineer-
ing [
strated that alginate gels support proliferation
of chondrocytes both in vitro and in vivo. New
cartilage tissue was formed when freshly iso-
lated calf chondrocytes mixed with alginate
solution were injected into mice subcutane-
ously [
].
Chitosan is a polycationic biopolymer
obtained by deacetylation of chitin, the main
component of the shell of crustaceans [
3
,
37
]. They have sol-gel transitions in
the range of
89
].
When ionically cross-linked, chitosan forms a
reversible hydrogel structure that is well suited
to a wide variety of pharmaceutical applica-
tions [
75
°C and form hydrogels
with relatively high strength. The thermo-
sensitivity of the polymers depends primarily
on the structure of the hydrophobic parts
of the oligopeptide side groups, which
may form strong physical junctions in the
polymer solution. The hydrophobic/hydro-
philic ratio plays an important role in estab-
lishing suitable properties for scaffolding
applications.
Among the natural polymers most frequently
proposed for injectable tissue-engineering
applications are alginates, collagen, chitosan,
hyaluronates, fi brin, and fi broin [
35
° to
43
]. Chitosan can be used as an
injectable carrier for tissue-engineering appli-
cations when covalently cross-linked in situ or
when an active particulate fi ller is used as a
reinforcing agent. Covalent cross linking of
chitosan has had limited success, because most
catalysts used for covalent cross linking are not
biocompatible [
6
,
16
,
17
,
93
]. Use of an active particulate
fi ller has met with some degree of success [
6
37
,
38
]. Chitosan-calcium phosphate composites
form injectable and moldable pastes at pH
values below
4
,
6
,
7
,
16
,
25
,
28
]. Alginates derived from brown
seaweed are anionic linear polysaccharides
composed of
,
37
,
57
,
60
,
91
and undergo a phase transi-
tion at physiological pH. The phase transition
entraps calcium phosphate within the hydrogel
matrix. Field emission micrography has shown
the resulting scaffold to have a highly porous
structure, with polymer strands that bind the
micrometer-sized aggregates of the ceramic
phase [
6
.
5
1
,
4
-linked
β
-D-mannuronate (M)
and
-L-guluronate (G) residues. A
cross-linked alginate hydrogel based on poly-
saccharides from seaweeds has been found
useful as a carrier for controlled release of ther-
apeutic peptides and proteins when the cross-
linking reaction is controlled in situ [
1
,
4
-linked
α
].
A photocross-linkable chitosan has been
used as a noninjectable carrier to induce neo-
vascularization in vivo and to regulate the
release of growth factors [
37
]. A
recent study has shown that alginate dialde-
hyde (ADA), an oxidized form of alginate in
combination with gelatin, can self-cross-link
in a controlled manner in the presence of small
concentrations of borax [
37
]. By introducing
lactose (lactobionic acid) moieties into the chi-
tosan molecules by means of a condensation
reaction with the amino groups, it proved pos-
sible to make an injectable chitosan/lactic acid
(CH-LA) scaffold. This involved dissolving the
polymer and mixing it with
44
]. A material suitable
for both drug-delivery and tissue-engineering
applications was injected with a double-syringe
fi brin glue applicator. One syringe was fi lled
with gelatin solution that contained the thera-
peutic agents, and the other was fi lled with the
oxidized alginate in the presence of borax. By
varying the concentrations of the reactants, the
gelation time within the hypodermic needle of
the applicator was varied from a few seconds to
less than a minute. Cells encapsulated in the gel
retained their protein-producing viability, and
the solidifi ed gel was completely degraded after
5
4
β
-FGF/FGF-
2
and
nonanticoagulant (IO
4
−
) heparin. When the
resulting hydrogel was injected into the right
and left sides of the backs of mice, the
β
-FGF/
FGF-
2
molecules, encapsulated by the chitosan/
(IO
4
−
) heparin hydrogel, were gradually
released as the gel was biodegraded, and there
was a “substantial effect to induce vasculariza-
tion and fi brous tissue formation” [
].
A thermosensitive chitosan hydrogel has
been prepared by grafting more than about
29
]. Another study confi rmed that
oxidized alginates rapidly degrade at physio-
logical pH [
weeks [
4
40
wt% of PEG to the chitosan chains via covalent
bonding [
]. Cytotoxicity screening using
mouse fi broblasts confi rmed the nontoxic
character of the gels. It has also been demon-
10
]. The resulting copolymeric hydro-
gel was injectable at low temperature and
7
