Stability of alginate-polyornithine microcapsules is profoundly dependent on the site of transplantation

Alginate encapsulation is a form of cell-based therapy with numerous preclinical successes but recalcitrant complications related to stability and reproducibility. Understanding how alginate stability varies across different transplant sites will help identify indications that might benefit most from this approach. Alginate stability has been quantified in the peritoneum, but there are no systematic studies comparing its relative stability across transplant sites. This study compares the stability of alginate-polycation microcapsules implanted in the peritoneum to those implanted in the brain and subcutaneous space at 14, 28, 60, 90, 120, and 180 days in-life. Using Fourier-Transform Infrared Spectroscopy (FTIR), the surface of explanted capsules was analyzed for the relative proportion of alginate (outer coat) and the polycationic polyornithine (middle coat). Using a mathematic relationship between FTIR peaks related to these two material components, an index was generated to compare the stability of four different alginates. A notable difference was observed with rapid breakdown in the peritoneum. Conversely, identical alginate capsules transplanted into the brain or subcutaneous space were stable for the 6 month study. These data suggest that (1) successful intraperitoneal transplantation requires modifications of the capsule configuration, the host environment, or both and (2) that sites such as the brain and subcutaneous space are inherently less hostile to conventional alginate capsule configurations.