Biomedical Engineering Reference
In-Depth Information
Synthetic and natural hydrogels have been
used for a wide variety of medical applications
[
In an earlier study, three OPF implants using
scaffolds of PEG(MW
930
)/OPF(MW
4470
) and
]. Among the synthetic
polymers considered for use as injectable car-
riers for tissue-engineering applications are a
variety of hydrophilic/hydrophobic diblock and
triblock copolymer combinations of poly(lactic
acid) (PLA), poly(glycolic acid) (PGA),
poly(lactic-co-glycolic) acid, (PLGA) and
poly(ethylene glycol) (PEG) [
4
,
6
,
11
,
37
,
54
,
62
,
91
one using a scaffold of PEG(MW
6090
)/
OPF(MW
14 430
) were implanted into holes
(
mm) drilled into the parietal cranial
bones of mature female New Zealand White
rabbits [
∼
6
.
3
90
]. The animals were sacrifi ced at
4
and
weeks, and the bones were sectioned
and analyzed histologically. In all implants, a
limited fi brous capsule formation was observed
after
12
46
,
47
,
48
,
49
,
50
,
51
,
61
] and copolymers of poly(ethyleneoxide)
(PEO) and (poly)propyleneoxide (PPO), under
the commercial names of Pluronics and Poly-
oxamer [
,
83
weeks. Low numbers of infl ammatory
cells and macrophages were seen at implant-
tissue interfaces; this observation confi rms
that the chemically cross-linked hydrogels
were evoking a mild tissue response. At
4
].
The use of cross-linkable polypropylene
fumarate as an injectable polymer to fi ll defects
in cancellous bone has been well documented
in the literature [
15
,
71
,
94
12
w e e k s , o n l y i m p l a n t s w i t h a s c a f f o l d o f P E G ( M W
6090
) exhibited a high number
of infl ammatory cells. The presence of infl am-
matory cells led to fragmentation of the hydro-
gel and extensive surface erosion. The authors
claim that the degradation rate can be con-
trolled by tailoring the macromolecular struc-
ture of the hydrogel, making it a desirable
material for a biodegradable scaffold for tissue
engineering [
)/OPF(MW
14 430
]. An oligomeric copoly-
mer synthesized from fumaryl chloride and
polyethylene glycol, oligo(poly(ethylene glycol)-
fumarate) (OPF), has been studied as an inject-
able carrier for cartilage tissue regeneration
[
82
,
96
]. The repeating glycol units on the
OPF impart water solubility to the material,
and the repeating fumarate double bonds facil-
itate cross linking. The material is injectable,
biodegradable, and cross-linkable in situ.
Gelatin microparticles loaded with transform-
ing growth factor
41
,
81
,
90
,
97
].
A thermoreversible copolymer, poly(N-iso-
propylacrylamide-co-acrylic acid) [P(NiPAAm-
co-AcA)], is a potential hydrogel carrier for
agents that promote soft-tissue renewal, spe-
cifi cally chondrocytes [
90
β
1
) were mixed with
OPF and a cross-linking agent poly(ethylene
glycol)diacrylate into a buffered saline phos-
phate solution that contained thermal radical
initiators and
β
1
(TGF-
]. The copolymer was
synthesized in solution by a free radical poly-
merization. The dynamic viscoelastic proper-
ties of a
45
9
×
10
6
chondrocyte cells/ml [
].
The suspensions were then injected into molds
to form individual hydrogel constructs. The
aim of the work was to determine the effect of
the microparticles and TGF-
81
M
phosphate-buffered saline) indicated a lower
critical solution temperature around
10
wt% solution of copolymer (in
0
.
1
°C and
a relatively sharp sol-gel transition at around
35
35
β
1
on the in vitro
proliferation and glycosaminoglycan (GAG)
production of chondrocytes encapsulated in
the hydrogels. A synergistic effect of having the
two components together in the hydrogel was
observed; the composite structures exhibited a
7
°C; the gel continued to harden further
over the next
.
5
°C. An important characteristic
of this gel is that it exhibits stability upon dilu-
tion, so that when gelled in situ it will not revert
to a liquid state. Fresh articular cartilage cells
from
3
-month-old New Zealand white rabbits
were suspended at a fi nal concentration of
12
-day
period, with signifi cant production in the fi rst
7
.
9
-fold increase in cell numbers over a
28
5
.
5
×
10
5
cells/ml in a
wt% P(NiPAAm-co-AcA)
solution, placed in culture plates, and gelled at
37
5
days, whereas control specimens containing
unloaded microparticles did not show signifi -
cant increases in the fi rst
°C. Cells recovered from the hydrogel cul-
tures over a
days, and their
production was slower overall than that of the
loaded microparticles. Control specimens
without microparticles did not exhibit signifi -
cant increases in cellularity over
14
-week period expressed the origi-
nal chondrocyte phenotype and displayed
typical chondrocytic morphology, in contrast
to those recovered from monolayer cultures,
which appeared to be more “fi broblast-like”
[
4
days. The
authors speculate that the gelatin microparti-
cles may promote cell proliferation by provid-
ing sites for chondrocyte attachment [
28
]. The material is injectable through small-
diameter needles and is not acutely toxic to
living cells. It therefore shows promise for
45
81
].
