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
porogen used to prepare 3D scaffolds remains. Therefore, <strong>the</strong> conventional method <strong>of</strong> porogen leaching by
washing with water is replaced by freeze-drying, facilitating <strong>the</strong> removal <strong>of</strong> <strong>the</strong> porogen and making
removal more complete. The method <strong>of</strong> porogen leaching by using ice particulates as <strong>the</strong> porogen material
can be employed to fabricate porous 3D scaffolds for tissue engineering. Using ice particulates as <strong>the</strong>
porogen material, scaffolds are prepared by mixing a polymer solution in a solvent with ice particulates,
freezing <strong>the</strong> mixture in liquid nitrogen, and freeze-drying. This method can be applied to biodegradable
polymers like polylactides that are soluble in a solvent such as chlor<strong>of</strong>orm or methylene chloride. Sieved ice
particles are dispersed in a polymer/chlor<strong>of</strong>orm solution. The ice particles are eventually leached out by
selective dissolution in water or by freeze-drying to produce a porous 3D scaffold as described in Figure 2.2:
(a)
(b)
(c)
(d)
(e)
(f)
Ice particulates are prepared by spraying deionised water into liquid nitrogen [Figure a].
Polymer solutions <strong>of</strong> various concentrations are prepared by dissolving different amounts <strong>of</strong>
polymer in solvent (e.g. methylene chloride or chlor<strong>of</strong>orm) and cooling. The sizes <strong>of</strong> <strong>the</strong> ice
particulates are controlled by <strong>the</strong> desirable sieving <strong>of</strong> <strong>the</strong> solution to −20°C [Figures b and c]. Ice
particulates are added to <strong>the</strong> precooled polymer solution.
The dispersion is gently vortexed [Figure d].
It is <strong>the</strong>n poured into a precooled designed mould [Figure e].
Subsequently, <strong>the</strong> mould with dispersion is frozen by placing at low temperature [Figure f].
The mould with dispersion is freeze-dried for a desirable time under low temperature [Figure g].
Often, fur<strong>the</strong>r drying at elevated temperatures is required to completely remove <strong>the</strong> solvent after
freeze-drying.
(a) Spraying (b) Sieving (c) Sieved Ice
particles
(d) Vortexing
(e) Moulding (f) Freezing (g) Freeze-drying
Figure 2.2: Procedure <strong>of</strong> ice particle–leaching.
[Kim et al., 2007b]
2.3 Gas-Foaming/Salt-Leaching Technique
The biodegradable scaffolds prepared by <strong>the</strong> particulate-leaching method <strong>of</strong>ten exhibit a dense
surface skin layer, which hampers in vitro cell seeding into <strong>the</strong> scaffolds and tissue ingrowth after in vivo
implantation. Additionally, poor interconnectivities between macropores lower cell viability and result in
non-uniform distribution <strong>of</strong> seeded cells throughout <strong>the</strong> matrix. Sodium bicarbonate salt or ammonium
bicarbonate salt with acidic excipients such as citric acid has been used for effervescent gas-evolving oral
tablets, due to its carbon dioxide – evolving property upon contact in acidic aqueous solution. Thus, various
alkalinising analgesic oral tablets are commercially available. In particular, ammonium bicarbonate salt –
upon contact in an acidic aqueous solution and/or incubated at elevated temperature – evolves gaseous
ammonia and carbon dioxide by itself.
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