Tissue Engineering Aspects of Neutral Networks

Macroporous Structure of Neutral PHEMA Containing Networks 

Since different crosslinking agents possess different solubilities in water, it was hypothesized that by altering the crosslinking agent used it should be possible to alter the networks pore morphology. Chirlia et al. (Clayton et al., 1997a,b Lou et al., 2000) performed a rather extensive evaluation of 

PHEMA solubility decreases with increasing ion concentration. As a result, Mikos et al. used salt solutions of varying ionic strength to dilute the reaction mixtures (Liu et al., 2000). It was noted that increasing the ion content of the aqueous solution to 0.7M, interconnected macropores were obtained at 60 vol% water. Surfactants may also be used to control the network pore structure. However, not much work has been done in this area, since surfactants typically work to reduce the surface repulsions between the two phases and form a uniform emulsion. These smaller emulsion droplets when gelled will create a network with an even smaller porous structure. Yet, this is still a promising area of exploration, since it may be possible to form alternate phase structures such as bicontinuous phases, which would be ideal for cellular invasion. 

Isotactic PHEMA was found to possess negative temperature dependence in water (Oh and Jhon, 1989). While atactic PHEMA is not expected to have a strong negative temperature dependence, the mechanisms of this behavior can still exist over short ranges and may effect the phase behavior. As such, increased temperatures may also function to control the pore morphology by allowing the polymer to phase separate early on in the reaction. 

Temperature not only plays a critical role with the thermodynamics, but also with the kinetics of the polymerization. Once phase separation occurs, the polymer phase will start to settle out of solution since it is denser than the aqueous phase. Chirlia noted this phenomenon by stating that in some reactions, a water layer was evident over the polymer sponge layer (Chirila et al., 1993). Temperature can reduce this settle-out by ramping up polymerization rate, and forcing gelation to occur sooner. 

Shwarkawy et al. (1997, 1998a,b) also demonstrated that changes in pore size not only effected vascular density but also the response to systemic uptake of drug through a vascularized implant. It was demonstrated that the 60 pm pore material deUvered the drug in almost half the time it took for a subcutaneous injection to be taken up systemically. This is due to the increased vascular density as well as increased vascular permeability at these pore sizes (Shwarkawy et al., 1997, 1998a,b). 

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