Tissue responses against immunoisolating alginate‐PLL capsules in the immediate posttransplant period

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Abstract
Alginate-polylysine (PLL) capsules are commonly applied for immunoisolation of living cells for the treatment of a wide variety of diseases. Large-scale application of the technique, however, is hampered by insufficient biocompatibility of the capsules with failure of the grafts as a consequence. Most studies addressing biocompatibility issues of alginate-PLL capsules have focused on the degree of overgrowth on the capsules after graft failure and not on the reaction against the capsules in the immediate posttransplant period. Therefore, capsules were implanted in the peritoneal cavity of rats and retrieved 1, 5, and 7 days later for histological examination and X-ray photoelectron spectroscopy analysis for evaluation of chemical changes at the capsule surface. After implantation, the nitrogen signal increased from 5% on day 0, to 8.6% on day 7, illustrating protein adsorption on the capsule's surface. This increase in protein content of the membrane was accompanied by an increase in the percentage of overgrown capsules from 0.5 ± 0.3% on day 1 to 3.3 ± 1.6% on day 7. The cellular overgrowth was composed of monocytes/macrophages, granulocytes, fibroblasts, erythrocytes, multinucleated giant cells, and basophils. This overgrowth was not statical as generally assumed but rather dynamic as illustrated by our observation that at day 1 after implantation we mainly found monocytes/macrophages and granulocytes that on later time points were substituted by fibroblasts. As the inflammatory reaction predictably interfere with survival of encapsulated cells, efforts should be made to suppress activities or recruitment of inflammatory cells. These efforts may be temporary rather than permanent because most inflammatory cells have disappeared after 2 weeks of implantation. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 62: 430–437, 2002