Lecture 6 - Porous Scaffold Fabrication

Question 1

Phase Separation in Polymer Solution

Answer 1

• For mixing of two components “1” (solvent or polymer) and “2” (polymer) to be spontaneous one must have deltaG_m < 0
• For single phase polymer solution (single phase mixture of polymer and solvent), changing conditions (such as T or conc.) may result in phase separation (from single phase into two)

Question 2

Morphology of Phase-Separated Polymer Solution

Answer 2

• Metastable region: nucleation, low polymer concentration results in minor polymer dispersed in solvent, high polymer concentration results in minor solvent dispersed in polymer
• Unstable region: spinodal decomposition

Question 3

Liquid-Liquid Phase Separation

Answer 3

• Reduction of polymer solubility when temperature is lowered
• Low T can damage biomolecules (still move around/crystallize)

Question 4

Solid-Liquid Phase Separation

Answer 4

• Solidification of solvent before liquid-liquid separation can occur
• Solvent must have crystallization T higher than liquid-liquid phase separation T
• Solvent crystallizes when T is decreased and polymer is expelled during crystallization
• When solvent is removed, scaffold then assumes pore morphology similar to solvent crystallite geometry

Question 5

Thermally Induced Phase Separation (TIPS)

Answer 5

• Involves dissolving of polymer in solvent at high T followed by phase separation induced by lowering solution T
• Forms polymer-rich phase and polymer-lean phase
• After removal of solvent by extraction, evaporation, or sublimation, it can form polymer scaffold

Question 6

Control of Scaffold Morphology and Pore Size

Answer 6

• Types of polymer (MW, viscosity, mechanics)
• Type of solvent
• Polymer concentration (push crystals out of way)
• Phase-separation T (rate of nucleation/crystal growth)
• Heat transfer direction (thermal gradient, crystal growth likes cold direction)

Question 7

Fabrication of Scaffold (Liquid-Liquid Phase Separation)

Answer 7

• Liquid-liquid phase separation
• Polyester (PLGA, PLLA and PDLLA) using dioxane/water (miscible) as solvent
• Use of amorphous polymers with slow cooling rate resulted in macroporous open pore structure, whereas semicrystalline polymer with fast cooling rate generated microporous closed pore structure
• Cell sizes in scaffolds dramatically increased with increasing quenching T, while they tended to assume more closed pore structure
• Increasing amounts of water in solvent mixture tended to generate large pore sizes (more crystal nucleation)

Question 8

Fabrication of Polyurethane Scaffold (Solid-Liquid Phase Separation)

Answer 8

Dissolve polyurethane in DMSO at 80C, freeze, dry

Question 9

Fabrication of PLGA Scaffold with Oriented Pores (Solid-Liquid Phase Separation)

Answer 9

• Thermal gradient to guide growth (nonhomogenous)
• Orientation structure of scaffold guided by solvent crystallization under certain T gradient
• Crystal growth favors lower T

Question 10

Affect of Polymer Concentration on Scaffold Morphology

Answer 10

• Increase in concentration of polymer solution, thickness of wall of formed pores (microtubules) increases and diameter of pores (microtubules) decreases
• Diameter of microtubules scaffolds decreases as T gradient increases
• Increased concentration, sidewalls become bigger and resist crystal growth
• Higher T gradient leads formation of many more crystal nuclei producing a higher crystallization speed, as result great number of smaller-sized crystals produced

Question 11

Scaffold with Fibrous Morphology (Liquid-Liquid Phase Separation)

Answer 11

• High gelation T, platelet-like (web-like) structures
• Low gelation T, nano-fibrous structures
• Porosity decreased with increasing polymer concentration