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Prevention of Morphological Changes in Alginate Microcapsules for Islet Xenotransplantation
  1. Hasan A. Hobbs,
  2. William F. Kendall Jr,
  3. Marcus Darrabie,
  4. Emmanuel C. Opara
  1. From the Department of Surgery (H.A.H., W.F.K., M.D.), Duke University Medical Center and the Veterans Administration Medical CenterDurham, NC. Duke University Medical Center and the Veterans Administration Medical Center (E.C.O.), Durham, NC.
  1. Address correspondence to: Emmanuel C. Opara, PhD, Box 3065, Duke University Medical Center, Durham, NC 27710.
  2. Supported in part by research funding from Microislet Inc, San Diego, Calif, and by the US Department of Veteran Health Affairs.
  3. Presented at the American Federation of Medical Research (AFMR) Symposium 1 of the Clinical Research 2001 Meeting held at the Crystal Gateway Marriott Hotel, Arlington, Va.

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.

Key Words
  • diabetes
  • islet transplantation
  • alginate
  • microcapsules
  • hydrophilicity

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