Prevention of morphological changes in alginate microcapsules for islet xenotransplantation

Background: Alginate microcapsule swelling, which occurs as a result of inc reased hydrophilicity owing to the Ca++ that remains after rapid chelation of the inner alginate core, is a problem in encapsulation. We have previous ly shown that exchange of the residual divalent Ca++ with the monovalent Na + through the use of 6 mmol/L Na2SO4 decreases swelling in chelated alginat e-polylysine-alginate microcapsules, and this process enhances their durabi lity. The purpose of the present study was to examine the morphology of Na2 SO4-treated microcapsules in long-term incubation with the use of serum-sup plemented culture medium. Methods: Spherical beads of purified alginate (3%) that were gelled with 1. 1% CaCl2 were first coated with polylysine, and then with 0.24% alginate. A fter rapid chelation of the inner alginate core with 55 mmol/L sodium citra te, the capsules were either incubated for 30 minutes in 6 mmol/L Na2SO4 or left untreated (control). Each group of capsules was then placed in a flas k containing Ham's culture medium supplemented with 20% porcine serum and i ncubated at 37 degreesC. Results: The diameters of Na2SO4-treated capsules only increased modestly f rom a mean +/- SD of 635 +/- 22.08 to 684.53 +/- 17.86 mum (P <0.0001) by d ay 7, with no further increases thereafter. In contrast, control capsules s howed a steady increase in their mean diameters, which changed from 639.55 +/- 21.44 to 735.48 +/- 108.85 mum (P <0.0001) by day 66. In addition, wher eas treated capsules remained spherical, control capsules showed progressiv e polymorphism. Conclusion: We have developed a new method of making more durable and stabl e microcapsules that can be used for islet cell xenotransplantation.