Preparation Of Immunoisolatory Membranes

The majority of thermoplastic ultrafiltration (UF) and microfiltration (MF) membranes used to encapsulate cells are manufactured from homogenous polymer solutions by phase inversion (47). Ultrafiltration membranes have pore sizes ranging from 5 nm to 0.1 ^m, while microfiltration (or microporous) membranes have pores ranging from 0.1 to 3 ^m. Phase inver

Figure 4 Diagram illustrating the different components of a macrocapsule contributing to successful implantation and cell viability. The manufacturing process involves several different aspects each with its own complexities. The initial choice of cell types includes primary, immortalized, or engineered. Intracapsular cell biology issues following encapsulation include a consideration of the need to use a compatible extracellular matrix and other considerations specific to that cell type because they impact cell nutrition and product synthesis. A series of other device-related issues include membrane geometry, morphology, and transport of molecules into and out of the device. Finally, the device must be sealed and, depending on the site of implantation, could require a tether for subsequent retrieval or the inclusion of radio-opaque markers for imaging purposes.

Figure 4 Diagram illustrating the different components of a macrocapsule contributing to successful implantation and cell viability. The manufacturing process involves several different aspects each with its own complexities. The initial choice of cell types includes primary, immortalized, or engineered. Intracapsular cell biology issues following encapsulation include a consideration of the need to use a compatible extracellular matrix and other considerations specific to that cell type because they impact cell nutrition and product synthesis. A series of other device-related issues include membrane geometry, morphology, and transport of molecules into and out of the device. Finally, the device must be sealed and, depending on the site of implantation, could require a tether for subsequent retrieval or the inclusion of radio-opaque markers for imaging purposes.

sion is a versatile technique that allows for the formation of membranes with a wide variety of nominal molecular weight cutoffs, permeabilities, and morphologies. The morphology and membrane properties depend on the thermodynamic parameters and kinetics of the fabrication process. In phase inversion, the polymer is first dissolved in an appropriate solvent. The solution is cast as a flat sheet or extruded as a hollow fiber. As part of the casting or extrusion procedure, the polymer solution is precipitated by a phase transition, which can be brought about by changing the temperature or solution composition. This process involves the transfer of a single-phase liquid polymer solution into a 2-phase system consisting of a polymer-rich phase that forms the membrane structure, and a second liquid polymer-poor phase that forms the membrane pores. Any polymer that will form a homogenous solution, which under certain temperatures and compositions will separate into 2 phases, can be used. Thermodynamic and kinetic parameters, such as the chemical potential of the components and the free energy of mixing of the components, determine the manner in which the phase separation takes place (48).

In cases where membrane strength limits the overall device strength, the membrane must be manufactured with certain considerations in mind, and the membrane dimensions, composition, and structure may have to be altered. Choosing a material that is inherently stronger (i.e., more ordered), or higher in molecular weight, with which to cast the membrane should increase the overall mechanical properties. UF or MF membranes can be fabricated with macrovoids within the wall or as an open-cell foam where the microvoids are interconnected. By incorporating techniques that increase the isoreti-culated structure within the membrane wall, the tensile strength can be increased with similar membrane porosity, thus maintaining the same overall diffusive transport. The strength also can be improved by increasing the cross-sectional area of the membrane by thickening the walls. Decreasing the overall membrane porosity increases the overall membrane strength. An example of a macrovoid-containing structure is presented in Fig. 5.

The outer morphology of the membranes can be altered during fabrication or by a posttreatment to improve the host tissue reaction. Using various phase inversion techniques, the outer surface of the membrane can range from a selectively permeable membrane ''skin'' to a structure large enough to allow cells to enter the wall (approximately 10-20 ^m in diameter). The combination of proper membrane transport and outer morphologies may also be achieved with composite membranes (49).

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