Influence of the Processes Parameters on the Properties of The ...

Chapter 2.
<strong>Processes</strong> to Manufacture Foams and to Functionalize <strong>the</strong> Surface
swelling/shrinking. Thermo-sensitive hydrogels made by physical cross-links between polymer chains are
very useful for injectable tissue engineering because no toxic organic cross-linkers are usually employed.
Polyphosphazenes are a new class <strong>of</strong> inorganic backbone polymers that are superior to many o<strong>the</strong>r
organic systems in term <strong>of</strong> <strong>the</strong>ir molecular structural diversity and property variations. These polymers can
be used as a reactive macromolecular intermediary by replacing chlorine atoms with organic side groups to
give various hydrolytically stable polymers.
The schematic reactions <strong>of</strong> injectable <strong>the</strong>rmosensitive gel are presented in Figure 2.10. Before <strong>the</strong>
reaction, L-isoleucine ethyl ester (IleOEt), glycolic or lactic acid ester and α-amino-ω-methoxy-polyethylene
glycol (AMPEG) are respectively dried for 1 day, at 50°C in vacuum, for moisture removal.
Tetrahydr<strong>of</strong>urane (THF) is dried by reflux over sodium/benzophenone under nitrogen atmosphere.
Triethylamine (TEA) and acetonitrile are distilled over baryum oxide (BaO) under nitrogen atmosphere. L-
isoleucine ethyl ester hydrochloride suspended in dry THF containing triethylamine is slowly added to
poly(dichloro-phosphazene) dissolved in dry THF. The reaction is performed for 4 hr at 4°C, and <strong>the</strong>n for 20
hr at room temperature. TEA and ethyl-2(O-glycol)lactate (GlyLacOEt) oxalic salt dissolved in acetonitrile
are added to this mixture, and <strong>the</strong> reaction mixture is stirred for 19 h at room temperature.
Figure 2.10: Reaction <strong>of</strong> injectable <strong>the</strong>rmosensitive gel.
[Song and Lee, 2007]
After AMPEG dissolved in dry THF-containing TEA is added to <strong>the</strong> polymer solution, <strong>the</strong>
reaction mixture is stirred for 2 days at 40°C–50°C. The above reaction mixture is filtered. After <strong>the</strong> filtrate
is concentrated, it is poured into n-hexane to obtain precipitate, which is reprecipitated twice in <strong>the</strong> same
solvent. The re-precipitated polymer is concentrated. The polymer product is fur<strong>the</strong>r purified by dialysis in
methanol for 4 days and <strong>the</strong>n in distilled water for 4 days at 4°C. The final dialysed solution is freeze-dried
to obtain <strong>the</strong> final polymer.
2.11 Liquid-Liquid Phase Separation Technique
A non solvent such as water is added to a polylactide solution in order to create an emulsion by
homogenizing <strong>the</strong>se two immiscible phases. A liquid-liquid phase separation occurs at a temperature higher
than <strong>the</strong> solvent crystallization temperature. Quenching <strong>the</strong>n locks in <strong>the</strong> emulsion liquid state structure.
Solvent and water are <strong>the</strong>n removed by freeze-drying to create porosity. Various factors, such as viscosity,
interfacial energy, polymer microstructure and concentration, must be controlled to stabilize <strong>the</strong> emulsion
with a continuous polymer-rich phase and a dispersed water phase [Schugens et al., 1996].
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