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

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Chapter 2.<br />

<str<strong>on</strong>g>Processes</str<strong>on</strong>g> to Manufacture Foams and to Functi<strong>on</strong>alize <str<strong>on</strong>g>the</str<strong>on</strong>g> Surface<br />

Liquid-liquid phase separati<strong>on</strong> gives rise to scaffolds with porosity up to 90% and an average pore<br />

size <str<strong>on</strong>g>of</str<strong>on</strong>g> 15 to 35 μm depending <strong>on</strong> <str<strong>on</strong>g>the</str<strong>on</strong>g> processing parameters and <str<strong>on</strong>g>the</str<strong>on</strong>g> <str<strong>on</strong>g>the</str<strong>on</strong>g>rmodynamics <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>the</str<strong>on</strong>g> polymer/solvent<br />

system. In comparis<strong>on</strong> to <str<strong>on</strong>g>the</str<strong>on</strong>g> previous technique, this method leads to scaffolds with a much larger surface<br />

area. However, <str<strong>on</strong>g>the</str<strong>on</strong>g> overall pore size is smaller, and organic solvents are still required. Both limit <str<strong>on</strong>g>the</str<strong>on</strong>g> use <str<strong>on</strong>g>of</str<strong>on</strong>g><br />

liquid-liquid phase separati<strong>on</strong> in <str<strong>on</strong>g>the</str<strong>on</strong>g> field <str<strong>on</strong>g>of</str<strong>on</strong>g> b<strong>on</strong>e tissue engineering [van de Witte et al., 1996].<br />

2.12 Solid-Liquid Phase Separati<strong>on</strong> Technique<br />

A polylactide-solvent soluti<strong>on</strong> is quenched below <str<strong>on</strong>g>the</str<strong>on</strong>g> melting point <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>the</str<strong>on</strong>g> solvent and dried under<br />

vacuum to remove <str<strong>on</strong>g>the</str<strong>on</strong>g> solvent by sublimati<strong>on</strong>. Solid–liquid phase separati<strong>on</strong>, with solvent crystallizati<strong>on</strong>,<br />

leads to ladder or sheet-like anisotropic morphologies, which str<strong>on</strong>gly depend <strong>on</strong> <str<strong>on</strong>g>the</str<strong>on</strong>g> quenching rate [Ma<br />

and Choi, 2001; Lo et al., 1995]. <strong>The</strong> ladder-like structure results from <str<strong>on</strong>g>the</str<strong>on</strong>g> forward progress <str<strong>on</strong>g>of</str<strong>on</strong>g> solvent<br />

crystallizati<strong>on</strong> fr<strong>on</strong>t [Schugens et al., 1996]. When <str<strong>on</strong>g>the</str<strong>on</strong>g> polymer c<strong>on</strong>centrati<strong>on</strong> increases, pore diameter and<br />

porosity tend to decrease. Porosity <str<strong>on</strong>g>of</str<strong>on</strong>g> 80−95%, with a pore size mainly between 20 and 100 μm and a<br />

compressive modulus up to 20 MPa in <str<strong>on</strong>g>the</str<strong>on</strong>g> l<strong>on</strong>gitudinal directi<strong>on</strong> could be obtained.<br />

This technique was also used to manufacture composite scaffolds, ei<str<strong>on</strong>g>the</str<strong>on</strong>g>r with hydroxyapatite<br />

[Zhang and Ma, 1999b]or Bioglass ® particles [Maquet et al., 2004; Boccaccini and Maquet, 2003]. Fillers<br />

were added to <str<strong>on</strong>g>the</str<strong>on</strong>g> polymer soluti<strong>on</strong> before quenching and solvent removal. Similar ladder-like anisotropic<br />

morphology was obtained, becoming more heterogeneous as filler c<strong>on</strong>tent was increased.<br />

2.13 Fibre Mesh/Fibre B<strong>on</strong>d<strong>on</strong>g Technique<br />

Fibres, produced by textile technology, have been used to make n<strong>on</strong>-woven scaffolds from PGA<br />

and P L LA [Cima et al., 1991]. <strong>The</strong> lack <str<strong>on</strong>g>of</str<strong>on</strong>g> structural stability <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>the</str<strong>on</strong>g>se n<strong>on</strong>woven scaffolds, <str<strong>on</strong>g>of</str<strong>on</strong>g>ten resulted in<br />

significant deformati<strong>on</strong> due to c<strong>on</strong>tractile forces <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>the</str<strong>on</strong>g> cells that have been seeded <strong>on</strong> <str<strong>on</strong>g>the</str<strong>on</strong>g> scaffold. This led<br />

to <str<strong>on</strong>g>the</str<strong>on</strong>g> development <str<strong>on</strong>g>of</str<strong>on</strong>g> a fibre b<strong>on</strong>ding technique to increase <str<strong>on</strong>g>the</str<strong>on</strong>g> mechanical properties <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>the</str<strong>on</strong>g> scaffolds<br />

[Mikos et al., 1993]. This is achieved by dissolving polylactide in methylene chloride and casting over <str<strong>on</strong>g>the</str<strong>on</strong>g><br />

polygycolide mesh. <strong>The</strong> solvent is allowed to evaporate and <str<strong>on</strong>g>the</str<strong>on</strong>g> c<strong>on</strong>struct is <str<strong>on</strong>g>the</str<strong>on</strong>g>n heated above <str<strong>on</strong>g>the</str<strong>on</strong>g> melting<br />

point <str<strong>on</strong>g>of</str<strong>on</strong>g> PGA. Once <str<strong>on</strong>g>the</str<strong>on</strong>g> PGA-P L LA c<strong>on</strong>struct has cooled, <str<strong>on</strong>g>the</str<strong>on</strong>g> P L LA is removed by dissolving in methylene<br />

chloride again. This treatment results in a mesh <str<strong>on</strong>g>of</str<strong>on</strong>g> PGA fibres joined at <str<strong>on</strong>g>the</str<strong>on</strong>g> cross-points [Sachlos and<br />

Czernuszka, 2003].<br />

B<strong>on</strong>ded PGA fibre structures with high and open porosity, a high area-to-volume ratio and pore<br />

diameters up to 500 μm were thus produced. <strong>The</strong>se biocompatible matrices, with structural integrity, are<br />

suitable as scaffolds for organ regenerati<strong>on</strong>. In additi<strong>on</strong>, <str<strong>on</strong>g>the</str<strong>on</strong>g> technique does not lend itself to easy and<br />

independent c<strong>on</strong>trol <str<strong>on</strong>g>of</str<strong>on</strong>g> porosity and pore size. Finally <str<strong>on</strong>g>the</str<strong>on</strong>g> combinati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> toxic chemicals and high<br />

temperature presents difficulties if cells or bioactive molecules, such as growth factors or proteins, are to be<br />

included in <str<strong>on</strong>g>the</str<strong>on</strong>g> scaffold during processing.<br />

2.14 Hydrocarb<strong>on</strong> Templating Technique<br />

By using a hydrocarb<strong>on</strong> particulate phase as a template it is also possible to form pore for a wide<br />

range <str<strong>on</strong>g>of</str<strong>on</strong>g> polymers. <strong>The</strong> use <str<strong>on</strong>g>of</str<strong>on</strong>g> hydrocarb<strong>on</strong> template allows for enhanced c<strong>on</strong>trol over pore structure,<br />

porosity, and o<str<strong>on</strong>g>the</str<strong>on</strong>g>r structural and bulk characteristics <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>the</str<strong>on</strong>g> polymer foam. Polymer foams have been<br />

produced with densities as low as 0.120, porosity as high as 87% and high surface areas (20 m 2 /g). Foams <str<strong>on</strong>g>of</str<strong>on</strong>g><br />

polylactides produced by this process have been used to engineer a variety <str<strong>on</strong>g>of</str<strong>on</strong>g> different structures, including<br />

tissues with complex geometries such as in <str<strong>on</strong>g>the</str<strong>on</strong>g> likeness <str<strong>on</strong>g>of</str<strong>on</strong>g> a human nose [Gibs<strong>on</strong> and Ashby, 1999; Yoda,<br />

1998; Szycher and Lee, 1992; Guidoin et al., 1988; Suh and Webb, 1988; Alsbjörn, 1984; Pruitt and Levine,<br />

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