Calcium Alginate

Abstract

The concept of using semipermeable capsules for delivery of therapeutic biological reagents was pioneered by T. M. S. Chang over 30 years ago (Chang 1964). Over the next 15 years, a number of immunoisolation systems were developed in an attempt to protect transplanted tissues or cells from host immune rejection; most of these were hollow fibers that were loaded with isolated pancreatic islets and then transplanted into diabetic rodents as bioartificial pancreas devices (Chick 1977, Tze 1976). In 1980, Lim and Sun successfully applied an alginate-polylysine microencapsulation system to islet transplantation in a rodent model (Lim and Sun 1980). This report attracted more attention to the concept of microencapsulation, especially the alginate-polylysine system. During the last 15 years, much effort has been devoted to the study of this system (reviewed by Lanza and Chick 1997). Most of the procedures for producing these microcap sules involve extruding a mixture of cells and sodium alginate into a divalent cation solution to form water-insoluble gel droplets. The negatively charged gel droplets are then coated with positively charged polymers, such as poly-L-lysine (PLL), through ionic interaction. The primary function of the coating is to form a strong complex membrane that reduces and controls the permeability of the alginate gel sphere. Recently, Lanza et al (1995a) reported prolongation of porcine and bovine islet xenograft survival in diabetic mice without immunosuppression, using uncoated alginate gel spheres—that is, alginate droplets that have under-gone gelation in calcium chloride but have not been coated with a synthetic PLL membrane. Sub-sequently, we applied this method to an even more discordant xenograft model, fish islets transplanted into rodents. In our laboratory, fish islet xenograft survival was significantly prolonged in both diabetic mouse and rat recipients without immunosuppression (Yang et al 1996, 1997b). Further studies revealed that uncoated alginate encapsulation, in combination with immunosuppression, permitted long-term fish islet xenograft survival in diabetic mice and rats (Yang et al 1996, Yang et al 1997b), as well as long-term islet allograft survival in spontaneously diabetic dogs (Lanza et al 1995b). It was surprising that uncoated alginate gel spheres could markedly prolong islet xenograft survival, because data clearly indicate that uncoated alginate gel has sufficient porosity to permit antibodies and complement to enter (Lanza et al 1995a, Martinsen et al 1992, Tanaka et al 1984). It is clear that the immunoprotective effect could not be explained solely by the capsule’s mechanical barrier (i.e., porosity of capsule versus molecular weight of diffusents) and that more complex mechanism(s), such as biological and diffusion modulation effects by the encapsulation materials, must also play significant roles. In this chapter, we will focus on technological advances and insights that have been gained through the study of uncoated calcium alginate gel encapsulation systems.