Fabrication Techniques and Properties of Scaffolds - Biodegradable Polymer-Based Scaffolds for Bone Tissue Engineering - page 20

2.1.3 Polymer Phase Separation
Phase separation was developed primarily to address the problem of drug
delivery (Lo et al. 1995 ; Whang et al. 1995 ). In order to achieve the goal to
deliver bioactive molecules from a degrading polymer scaffold to cells within
or surrounding the scaffold which can potentially allow manipulation of tissue
growth and cell function, the scaffold manufacturing process must lend itself
to incorporate bioactive molecules and must not cause any loss of drug activity
due to exposure to harsh chemical or thermal environments. Using the phase
separation technique, porous PLLA and poly(phosphoester) scaffolds with
small hydrophilic and hydrophobic bioactive molecules was manufactured.
First, the polymer was dissolved in a solvent at a low temperature, and then
the bioactive molecule was dissolved or dispersed in the resulting homogene-
ous solution, which was then cooled in a controlled fashion until solid-liquid
or liquid-liquid phase separation was induced. The resulting bicontinuous
polymer and solvent phases were then quenched to create a two phase solid.
By sublimation, solidified solvent was then removed, leaving a porous polymer
scaffold with bioactive molecules incorporated within the polymer. To incor-
porate small molecules into the polymer scaffolds, this technique was proved
useful.
Thermally induced phase separation (TIPS) of polymer solution was
reported to be used in the field of drug delivery and to fabricate microspheres
in order to incorporate biological and pharmaceutical agents (Ma 2004 ). In
order to fabricate tissue engineering scaffolds, this process has become much
popular. By altering the types of polymer and solvent, polymer concentration
and phase separation temperature, different types of porous scaffolds with
micro and macro-structured foams can be produced. In order to control pore
morphology on a micrometer to nanometer level, TIPS process can be utilized
(Ma 2004 ).
Depending on the thermodynamics and kinetic behaviour of the polymer
solution under certain conditions, TIPS can be a complicated process (Chen and
Ma 2005 ). It was defined that if a system where the solvent crystallization tem-
perature (freezing point) is higher than the liquid-liquid phase separation tempera-
ture, the system can separate by lowering the temperature, the process is called
solid-liquid phase separation. After the removal of the solvent, the remaining
pores have morphologies similar to solvent crystallite geometries. On the other
hand, when the solvent crystallization temperature is much lower than the phase
separation temperature, if the temperature of polymer solution is decreased, a
liquid-liquid phase separation takes place.
Figure 2.1 is the schematic phase diagram for a binary polymer-solvent sys-
tem. A strongly asymmetric phase diagram is typical for a solution where a pol-
ymer is in a solvent of lower molecular mass. The solution is in the one-phase
region and homogeneous at high temperature. A liquid-liquid phase separation
to polymer-lean and polymer-rich phases can take place when a homogeneous