Info

NaCI/HEPES ™ Wash pH 7.0

l_ Alginate /

Adsorption

Aspirate —

NaCI/HEPES y Wash pH 7.4

± Citrate

Aspirate —

NaCI/HEPES ~ Wash pH 7.4

Cell-loaded Microcapsules in Culture Medium

Figure 2 Flow diagram outlining the steps involved in the microencapsulation of cells. The poly(L-lysine) and alginate are sequentially adsorbed onto the alginate microspheres following immersion in a water bath.

and provides the barrier paramount for successful immunoisolation.

A second method of macroencapsulation, called coextru-sion, avoids the sealing problem by entrapping cells within the lumen of a hollow fiber during the fabrication process (32). Pinching the fiber before complete precipitation of the polymer causes fusion of the walls, providing closure of the

Figure 3 Schematic illustration of a syringe pump extrusion technique for encapsulating cells within alginate microcapsules. The alginate/cell suspension is extruded through the center of the annular spinneret, whereas filtered nitrogen is passed through a surrounding outer tube. In this manner, droplets are sheared off the spinneret assembly and dropped into a container of CaCl2.

Figure 3 Schematic illustration of a syringe pump extrusion technique for encapsulating cells within alginate microcapsules. The alginate/cell suspension is extruded through the center of the annular spinneret, whereas filtered nitrogen is passed through a surrounding outer tube. In this manner, droplets are sheared off the spinneret assembly and dropped into a container of CaCl2.

extremities while the cells are inside. The advantages of coex-trusion over loading preformed capsules are that the cells are distributed more uniformly along the entire length of the fiber and shear stresses on the cells are reduced during the loading process. In addition, the coextrusion process offers the potential for mass production of cell-loaded capsules.

Several modifications to macrocapsule configurations have been designed to provide added strength to ensure device integrity. It is important for the encapsulating membrane to exhibit enough compliance to meet the dynamics of the surrounding tissue, thus not eliciting a foreign body reaction, yet mechanically resilient to resist failure during device implantation/retrieval. Mechanical supports to provide added strength to the membrane/device are better served from within the device to therefore not impede diffusion between the encapsulating membrane and the surrounding tissue. One approach includes the addition of a cross-linked hydrogel (e.g., a 2% alginate solution) within the device. This modification was observed to enhance structural support during the implantation procedure (33). However, with time the hydrogel loses structural integrity and does not provide added strength, especially with regard to tensile strength, an important consideration for device retrieval.

The ability to retrieve devices, or remove the cellular contents from within, are important safety considerations for potential complications such as brain edema following implantation, contamination, dosing modifications, or patient request. Early designs were based on a semipermeable receptacle (16) or U-shaped configuration (32) attached to the host skull. These configurations offered the ability to empty and refill the devices, or retrieve the devices themselves, without dis rupting the host brain with additional neurosurgical procedures. However, devices secured to the skull could exhibit mechanical perturbations to the host tissue due to mechanical noncompliance and elicit an elevated foreign-body reaction from the host. Other configurations with internal supports have included titanium wires and braided materials to provide added tensile strength during device retrieval. Devices incorporating a titanium wire could be associated with mechanical noncompliance within the device, rendering the flexible membrane susceptible to damage. In contrast, the incorporation of braided materials within the tubular device has provided a material compliant with the membrane that enhances the tensile strength of the device.

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