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

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iological performance. Biocompatibility <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>the</str<strong>on</strong>g> scaffold is critical and must not damage cells and alter <str<strong>on</strong>g>the</str<strong>on</strong>g>ir<br />

functi<strong>on</strong>s or lead to significant scarring.<br />

A number <str<strong>on</strong>g>of</str<strong>on</strong>g> biodegradable scaffolds are described in <str<strong>on</strong>g>the</str<strong>on</strong>g> literature. Most <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>the</str<strong>on</strong>g>se scaffolds come<br />

from <str<strong>on</strong>g>the</str<strong>on</strong>g> family <str<strong>on</strong>g>of</str<strong>on</strong>g> polyesters. Poly(α-hydroxy acids) like poly(lactic acid) (PLA), poly(glycolic acid)<br />

(PGA), and <str<strong>on</strong>g>the</str<strong>on</strong>g> co-polymer, known as poly(lactic-co-glycolic acid) (PLGA) are a part <str<strong>on</strong>g>of</str<strong>on</strong>g> tissue engineering<br />

studies. <strong>The</strong> comm<strong>on</strong> use <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>the</str<strong>on</strong>g>se polymers is basically related to <str<strong>on</strong>g>the</str<strong>on</strong>g>ir degradati<strong>on</strong> behaviour. Polymer<br />

degradati<strong>on</strong> takes place mostly through scissi<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>the</str<strong>on</strong>g> main chains or side-chains <str<strong>on</strong>g>of</str<strong>on</strong>g> polymer molecules,<br />

induced by <str<strong>on</strong>g>the</str<strong>on</strong>g>ir <str<strong>on</strong>g>the</str<strong>on</strong>g>rmal activati<strong>on</strong>, oxidati<strong>on</strong>, photolysis, radiolysis, or hydrolysis. Some polymers undergo<br />

degradati<strong>on</strong> in biological envir<strong>on</strong>ments when living cells or microorganisms are present around <str<strong>on</strong>g>the</str<strong>on</strong>g><br />

polymers. PLA degrades into lactic acid, and PLGA degrades into lactic and glycolic acid. Also, for PLGA,<br />

<str<strong>on</strong>g>the</str<strong>on</strong>g> degradability rate can be c<strong>on</strong>trolled by changing <str<strong>on</strong>g>the</str<strong>on</strong>g> co-m<strong>on</strong>omer compositi<strong>on</strong>. Fur<str<strong>on</strong>g>the</str<strong>on</strong>g>rmore, PLA and<br />

PLGA are approved by United States Food and Drug Administrati<strong>on</strong> for biomedical uses [Ikada and Tsuji,<br />

1999; Steinbüchel, 2003].<br />

Supercritical CO 2 (scCO 2 ) foaming was first proposed by Mo<strong>on</strong>ey et al. [1996] to create porous<br />

PLGA and PLA scaffolds by <str<strong>on</strong>g>the</str<strong>on</strong>g> pressure quench method, which was first proposed by Goel and Beckman<br />

[1994] to manufacture microcellular PMMA foams. <strong>The</strong>re have been a number <str<strong>on</strong>g>of</str<strong>on</strong>g> followers, which worked<br />

<strong>on</strong> foaming <str<strong>on</strong>g>of</str<strong>on</strong>g> biodegradable polymers to create porous scaffolds by this method [Reverch<strong>on</strong> and Cardea,<br />

2007a; Tsivintzelis et al., 2007a; Quirk et al., 2004a; Goel and Beckman, 1994a, 1995; Khang et al., 2007].<br />

Supercritical CO 2 is a green solvent and this method c<strong>on</strong>sists in using CO 2 as a blowing agent for<br />

<str<strong>on</strong>g>the</str<strong>on</strong>g> polymer to create porous material. CO 2 is used because it is relatively n<strong>on</strong>-toxic, relatively inert, and n<strong>on</strong><br />

combustible. Also, it has relatively reachable critical points (T c = 31°C and P c = 73.8 bars). Thus it can be<br />

used to prepare microcellular foams using supercritical fluids as foaming agents. It has many advantageous<br />

properties, which enable <str<strong>on</strong>g>the</str<strong>on</strong>g>ir use as foaming agents; <str<strong>on</strong>g>the</str<strong>on</strong>g>se include a tuneable solvent power, <str<strong>on</strong>g>the</str<strong>on</strong>g><br />

plasticizati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> glassy polymers (as a c<strong>on</strong>sequence <str<strong>on</strong>g>of</str<strong>on</strong>g> glass transiti<strong>on</strong> temperature depressi<strong>on</strong>) and enhanced<br />

diffusi<strong>on</strong> rates. <strong>The</strong> low critical temperature <str<strong>on</strong>g>of</str<strong>on</strong>g> CO 2 allows an easy and complete separati<strong>on</strong> from <str<strong>on</strong>g>the</str<strong>on</strong>g><br />

polymer, without a vapour-liquid transiti<strong>on</strong> during <str<strong>on</strong>g>the</str<strong>on</strong>g> expansi<strong>on</strong>. General principle <str<strong>on</strong>g>of</str<strong>on</strong>g> foaming method is<br />

<str<strong>on</strong>g>the</str<strong>on</strong>g> following: saturati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> pellets with CO 2 at desired temperature and high pressure, followed by a rapid<br />

depressurizati<strong>on</strong> which causes <str<strong>on</strong>g>the</str<strong>on</strong>g> super saturati<strong>on</strong>. As a result <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>the</str<strong>on</strong>g> super saturati<strong>on</strong>, <str<strong>on</strong>g>the</str<strong>on</strong>g> creati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>the</str<strong>on</strong>g><br />

nuclei occurs and <str<strong>on</strong>g>the</str<strong>on</strong>g> depressurizati<strong>on</strong> induced desorpti<strong>on</strong> from <str<strong>on</strong>g>the</str<strong>on</strong>g> polymer matrix and <str<strong>on</strong>g>the</str<strong>on</strong>g> phase change <str<strong>on</strong>g>of</str<strong>on</strong>g><br />

CO 2 provides <str<strong>on</strong>g>the</str<strong>on</strong>g> pore growth.<br />

<strong>The</strong> solubility <str<strong>on</strong>g>of</str<strong>on</strong>g> CO 2 increases with pressure, which leads to work at supercritical pressures.<br />

Moreover, since <str<strong>on</strong>g>the</str<strong>on</strong>g> critical temperature <str<strong>on</strong>g>of</str<strong>on</strong>g> CO 2 is 31°C, it can be used to process <str<strong>on</strong>g>the</str<strong>on</strong>g>rmally sensitive<br />

materials. Sorpti<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> CO 2 into <str<strong>on</strong>g>the</str<strong>on</strong>g> polymers depresses <str<strong>on</strong>g>the</str<strong>on</strong>g>ir glass transiti<strong>on</strong> temperature which results in a<br />

polymer/gas soluti<strong>on</strong>.<br />

On <str<strong>on</strong>g>the</str<strong>on</strong>g> o<str<strong>on</strong>g>the</str<strong>on</strong>g>r hand, in <str<strong>on</strong>g>the</str<strong>on</strong>g> tissue engineering field, as CO 2 replaces <str<strong>on</strong>g>the</str<strong>on</strong>g> chemical solvents, it<br />

provides <str<strong>on</strong>g>the</str<strong>on</strong>g> complete disappearance <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>the</str<strong>on</strong>g> residual amounts <str<strong>on</strong>g>of</str<strong>on</strong>g> undesired substances in <str<strong>on</strong>g>the</str<strong>on</strong>g> scaffolds <str<strong>on</strong>g>of</str<strong>on</strong>g><br />

biomedical use. <strong>The</strong> manufacturing methods are very important for <str<strong>on</strong>g>the</str<strong>on</strong>g> specific organs because <str<strong>on</strong>g>the</str<strong>on</strong>g><br />

physicochemical properties <str<strong>on</strong>g>of</str<strong>on</strong>g> scaffold matrices — such as porosity, equivalent pore diameter, and specific<br />

area — are determined by <str<strong>on</strong>g>the</str<strong>on</strong>g> manufacturing methods.<br />

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