Prevention of Morphological Changes in Alginate Microcapsules for Islet Xenotransplantation

Abstract

Background

Alginate microcapsule swelling, which occurs as a result of increased hydrophilicity owing to the Ca⁺⁺ that remains after rapid chelation of the inner alginate core, is a problem in encapsulation. We have previously shown that exchange of the residual divalent Ca⁺⁺ with the monovalent Na⁺ through the use of 6 mmol/L Na₂SO₄ decreases swelling in chelated alginate-polylysine-alginate microcapsules, and this process enhances their durability. The purpose of the present study was to examine the morphology of Na₂SO₄-treated microcapsules in long-term incubation with the use of serum-supplemented 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. After rapid chelation of the inner alginate core with 55 mmol/L sodium citrate, 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 flask containing Ham's culture medium supplemented with 20% porcine serum and incubated at 37°C.

Results

The diameters of Na₂SO₄-treated capsules only increased modestly from a mean±SD of 635±22.08 to 684.53±17.86 μm (P <0.0001) by day 7, with no further increases thereafter. In contrast, control capsules showed a steady increase in their mean diameters, which changed from 639.55±21.44 to 735.48±108.85 μm (P<0.0001) by day 66. In addition, whereas treated capsules remained spherical, control capsules showed progressive polymorphism.

Conclusion

We have developed a new method of making more durable and stable microcapsules that can be used for islet cell xenotransplantation.