Phase separation is a homogeneous multicomponent system, just like a polymer- water emulsion, which becomes thermodynamically unstable under certain conditions and tends to separate into more than one phase for lowering the system free energy . A polymer solution separates into two phases, one having low polymer concentration (polymer lean phase) and other having the high polymer concentration (polymer rich phase). The polymer is dissolved in phenol or naphthalene, and then the biologically active molecules are dispersed in these solutions. By lowering the temperature, the liquid-liquid phase is separated by lowering the temperature and quenching the mixture below the freezing point of the solvent to form a two-phase solid, followed by freeze-drying to produce porous scaffolds, in which the biologically active molecule is integrated into the structure [166, 178, 179]. The architecture of the scaffold could be controlled by various thermodynamic and kinetic parameters, such as the selection of solvent phase separation temperature. Phase-separation technique can be used to fabricate scaffolds from many types of polymers and polymeric composite materials . Phase separation, as one of the common technologies for fabricating various composites, is also considered to be an effective means of developing a reinforcing material to provide adequate topographical architecture and mechanical properties of scaffolds for tissue regeneration. There are many studies on the applications of reinforced scaffolds prepared by phase separation. Bonnaud et al.  studied the effect of reinforcing glass fibers on morphology and properties of thermoplastic modified epoxy-aromatic diamine matrix prepared by the phase separation. Ma et al.  prepared the highly porous CNTs reinforced thermoplastic PLLA nanocomposite scaffold by a thermally induced phase separation method. Nakhoda et al.  designed a new class of PU biocomposites reinforced with green biocellulose nanofibers (BC), and the porosity
Fig. 2.9 Fabrication of TPU/CNTandTPU/NFC scaffolds using thermally induced phase separation via different solvent removal methods  (Adapted with permission from Ref. . Copyright 2016 Elsevier Ltd)
was introduced in the PU matrix using a combination of salt leaching and thermally induced phase separation (TIPS). Mi et al.  prepared the TPU/CNT and TPU/ NFC scaffold by using thermally induced phase separation based on different solvent removal methods (Fig. 2.9). Tian et al.  built TiO2 nanoparticle reinforced PLLA/TiO2 porous scaffolds by using thermally induced phase separation (TIPS) and further examined the influence of TiO2 contents on the physicochemical properties of porous scaffolds.
The advantage of the phase separation technique is that it can easily combine with other fabrication technology, such as particulate leaching or rapid prototyping, to create 3D scaffolds for tissue engineering applications . However, the disadvantage of this technique is that the pores have a diameter on the order of a few to tens of microns and are usually unevenly distributed, which limits its applications in tissue engineering.