Biomedical Engineering Reference
In-Depth Information
3.4 Gene Delivery
Localized release of plasmid DNA or polymer/DNA complexes was performed
by using biodegradable thermogelling hydrogels of poly(organophosphazenes) as
release matrices. The complexes between galactosylated chitosan-graft-polyeth-
ylenimine (GC-
g
-PEI) were loaded within the thermosensitive hydrogels based
on polymer
18
as a hepatocyte targeting gene delivery system [
72
]. The hydro-
gel loaded with GC-
g
-PEI/DNA complexes showed low cytotoxicity and higher
transfection efficiency than PEI/DNA complexes only. The in vivo distribution
study showed the specific accumulation of the released GC-
g
-PEI/DNA com-
plexes in the liver, indicating better hepatocyte targeting and gene delivery. On the
other hand, a low molecular weight PEI grafted poly(organophosphazenes) with
a cleavable ester linkage formed a polyplex with siRNA of cyclin B1 with the
size of 100 nm [
132
]. The polyplex aqueous solution underwent a sol-gel tran-
sition at physiological conditions. The polyplex-protected siRNA exhibited the
enhanced stability up to 30 days in the presence of serum, compared with naked
siRNAs, which showed degradation after 1 h. The release mechanism of the poly-
plexes was dominated by both dissolution and degradation of the polyplex hydro-
gel. The results showed an in vivo antitumor effect via cyclin B1 gene silencing
for 4 weeks with only a single injection, indicating the polyplex hydrogel as an
alternative siRNA carrier for many diseases that require localized and long-term
therapy [
132
].
3.5 Tissue Engineering
Biodegradable thermogel formed from polymer
15
was employed to entrap islets
of Langerhans in an artificial pancreas [
73
]. A prolonged insulin secretion in
response to basal glucose concentration was observed from the rat islets entrapped
in the hydrogel compared to free rat islets and islets entrapped in other types of
polymer gels. The rat islets in the hydrogel showed higher cell viability and insu-
lin production over a 28-day culture. The studies indicated that the thermosensitive
injectable, biodegradable matrix from poly(organophosphazenes) can be used with
several cell types as culture matrix. In addition, the hydrogels based on polymer
15
was also employed to entrap primary rat hepatocytes, cultivated as spheroids
in order to examine differentiation morphology and enhanced liver-specific func-
tions [
133
]. In a 28-day culture period, the spheroidal hepatocytes entrapped in
the gel maintained a higher viability and produced albumin and urea at constant
rates, indicating the potential application of poly(organophosphazene) hydro-
gel as a three-dimensional cell system for bioartifical liver devices and bioreac-
tors. Furthermore, an injectable, thermogelling poly(organophosphazene)-RGD
conjugate was developed for the enhancement of mesenchymal stem cell osteo-
genic differentiation [
65
]. The conjugate was synthesized by attaching RGD on
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