Biomedical Engineering Reference
In-Depth Information
expression of the encapsulated chondrocytes. We also reported that a block copol-
ymer system of PDP and PEG exhibited temperature-responsive sol-gel transition.
One of the merits of PDPs for design of temperature-responsive polymers compared
with simple aliphatic polyesters is that the hydrophobicity can be controlled by
choosing the amino acids [
316
]. Song and coworkers have shown a potential utility
of polyphosphazene-based IP hydrogel system as a vehicle for cell delivery in cell-
based therapy. They prepared a hydrogel entrapping pancreatic islets using temper-
ature-responsive polyphosphazene. Rat islets in the hydrogel showed higher cell
viability and insulin production over 28 days as compared to those for free rat islets
[
317
]. In a subsequent study, polyphosphazene hydrogels were used to encapsulate
hepatocytes as spheroids or single cells. The spheroid hepatocytes maintained a
higher cell viability and produced albumin and urea over 28 days [
318
].
Some graft-type biodegradable copolymers were reported as thermo-gelling
systems. We synthesized amphiphilic PLA-
g
-PEG by a coupling reaction of random
copolymer of LA and DP having carboxylic acid side chains [poly(Glc-Asp)-
co
-LA] [
111
]. The obtained amphiphilic graft copolymers showed temperature-
responsive sol-gel transition behavior and higher mechanical strength compared
with usual linear block copolymer systems. Jeong and coworkers have demonstrated
sustained release of insulin from a hydrogel of a PLGA-
g
-PEG/PEG-
g
-PLGA
mixture [
319
]. After a single injection of insulin-containing PLGA-
g
-PEG aqueous
solution, blood glucose levels could be adjusted for 5-16 days in diabetic rats. They
also reported that chondrocyte-loaded PLGA-
g
-PEG hydrogels were useful to repair
an articular cartilage defect [
319
]. The cartilage defect was completely repaired
by PLGA-
g
-PEG hydrogel. The superior efficacy for cartilage defect repair was
attributed to the favorable degradation profile of PLGA-
g
-PEG.
Usual linear triblock copolymer thermo-gelling systems have problems of low
mechanical strength in the gel state. The storage moduli of linear IP systems in the gel
state are usually less than 100 Pa. Multiblock copolymers and graft copolymers have
somewhat improved mechanical strength. Recently, we have developed an IP system
based on star-shaped branched block copolymers to improve mechanical strength. The
branched structure should lead to efficient physical crosslinking during the gel forma-
tion. We synthesized eight-armPEG-
b
-PLLA having a star-shaped branched structure
using octa-functional PEG (eight-armPEG) as macro-initiator [
171
-
173
], then hydro-
phobic cholesterol groups were attached to some of the ends of the star-shaped block
copolymer to give eight-arm PEG-
b
-PLLA-cholesterol [
320
]. An aqueous solution of
eight-arm PEG-
b
-PLLA-cholesterol (above 3 wt% in polymer concentration)
exhibited temperature-responsive instantaneous gelation at 36
Cuponhea ing
(Fig.
21
), but the virgin eight-arm PEG-
b
-PLLA did not gel at any concentrations.
The eight-arm PEG-
b
-PLLA-cholesterol showed significantly higher mechanical
strength (storage modulus 5,000 Pa) compared with previous biodegradable thermo-
gelling polymers. We then investigated the potential of the IP system as an injectable
scaffold for tissue engineering. L929 cells encapsulated into the hydrogel were viable
and proliferated three-dimensionally in the hydrogel, suggesting that the extracellular
matrix (ECM)-like network structure of the hydrogel guided L929 cells into three-
dimensional proliferation. The 10 wt% hydrogel eroded gradually in PBS at 37
C
