Biomedical Engineering Reference
In-Depth Information
(Pluronic
TM
), have been reported to use for drug delivery and tissue engineering,
most of these materials suffer from non-biodegradability, non-biocompatibility,
toxicity, and poor mechanical properties [
4
,
20
,
24
,
25
]. To address this issue, bio-
degradable reverse thermogelling polymers based on polyester and PEG, such as
poly(ethylene glycol)-
b
-poly(L-lactic acid)-
b
-poly(ethylene glycol) (PEG-
b
-PLLA-
b
-PEG), were developed. [
18
,
20
-
23
]. These novel thermogelling polymers exhibit
multiple desired functionalities as ideal materials for injectable in situ forming
hydrogels, including good biocompatibility, tunable drug release and degradation
rate, improved mechanical properties and capability of encapsulating various drugs.
However, the acidic degradation products from the polyester may cause tissue
necrosis or irritation around the implant site as well as denaturation of the incorpo-
rated biopharmaceuticals. Therefore, there is still room for improving the current
block copolymer hydrogels to meet the physiological and practical requirements.
As an alternative, poly(organophosphazenes) have been gaining significant atten-
tion in the biomedical field, because they can offer a number of crucial advantages
for biological research and biomedical applications [
26
-
28
]. High molecular weight
poly(organophosphazenes) are inorganic backbone polymers with an essentially
linear backbone of alternating phosphorus and nitrogen atoms and two organic or
organometallic side groups linked to each phosphorus atom [
29
-
31
]. Therefore,
the polymer properties can be precisely tailored through changes in the side groups
to optimize properties for specific biomedical applications. For example, hydro-
phobic poly(organophosphazenes) with fluoroalkoxy or aryloxy side groups have
been evaluated as bioinert biomaterials for use in prosthetic blood vessels, artificial
heart membranes, artificial heart valves, dental filling materials and soft denture lin-
ers [
32
-
34
]. On the other hand, a growing number of poly(organophosphazenes)
have been designed specifically to be hydrolytically sensitive as biodegradable
materials. Unlike polyesters, poly(organophosphazenes) can hydrolyze into non-
toxic products, like phosphate, ammonium ion and free organic side groups, with
near-neutral pH values [
35
]. The organic side groups of the hydrolytically sensi-
tive poly(organophosphazenes) range from amino acid ester (
1
) [
36
-
40
], dipeptides
(
2
) [
41
-
44
], depsipeptides (
3
) [
45
-
47
], to other benign or physiologically essential
molecules (
4-6
) [
48
-
54
]. Several examples are shown in Fig.
2
.
The objective of this chapter is to provide a comprehensive summary
of the preparation and application of biodegradable reverse themogelling
poly(organophosphazenes), including polymer design, property assessment and
potential biomedical applications.
2 Design of Biodegradable Thermogelling
Poly(Organophosphazenes)
By far the largest effort to construct biodegradable thermogelling
poly(organophosphazenes) has been reported by Song and coworkers. The gen-
eral molecular structures of these poly(organophosphazenes) consist of a short
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