Cellular microencapsulation was first developed for the purpose of immunoisolating foreign cells beyond in vivo implantation for a variety of therapeutic applications. Encapsulation of pancreatic islets to provide a sustainable insulin depot for diabetic patients was among the most widely publicized. Type I diabetes is an autoimmune disorder in which the patient's own immune system attacks the islet cells that produce insulin. Encapsulation of the cultured islet cells in a thin shell is safe from the immune response but is permeable to insulin, nutrients, and other metabolic necessities (Orive et. al., 2003).
A second important application of cell encapsulation involves hepatocytes - among the most difficult cells to culture. In lieu of allotransplantation, individuals suffering fromliver dysfunction have limited options. Bioartificial Liver Assist Devices (BLAD) have been developed for the purpose of aiding a failing liver via perfusion of blood plasma through an extracorporeal device in which hepatocytes are encapsulated within a three-dimensional microenvironment, promoting normal functions such as detoxification, excretion, and metabolism.
First generation BLAD were hollow cartridges housing hepatocytes cultured in the luminal space. However, recently, there have been efforts to encapsulate the hepatocytes within the BLAD. This is to protect the hepatocytes from immune responses and shear forces (Patzer et. al., 2001). Microcapsules for cellular encapsulation are produced using a variety of technologies, ranging from manual dispensation of a polyelectrolyte/cell suspension into a receiving solution, to emulsification of thermally sensitive polymeric solutions. The breadth of encapsulation technologies used for this specialized application is limited principally by the requirements of the encapsulated cells.
Subsequently, nearly all solutions involved are aqueous, and those that aren't must be water immiscible and biocompatible (e.g. oils such as dimethyl polysiloxane, used in the case of emulsions). Additionally, solution osmolarity can not stray far from physiological (300 mOsm), and mechanical stresses must be limited so as not to rupture cell membranes during microcapsules production. Finally, limitations specific to cell types must be taken into consideration - for instance, calcium ion concentrations usually ranging from 0.1 to 2 wt% when alginate are employed for cell encapsulation; however, stem cells are known to be sensitive to transmembrane calcium gradients and so the application presents obstacles that otherwise, in the case of most terminally differentiated cells types, would be negligible (Ciccolini et. al., 2003).
A final, categorically important consideration for cellular encapsulation is the compromise between size and sustainable mass transport. Cells towards the inside of a capsule must also be able to exchange molecules over a large range of sizes, from soluble gases to large signaling proteins, depending on the specific application. If the capsule is too large to sustain sufficient passive (diffusion-based) mass transport given the permeability of the encapsulating medium, cells towards the inside of the cell may not develop as intended or may perish leading to the necrotic microcapsule cores.