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Keywords:

  • cytoprotective coating;
  • hydrogen-bonding;
  • layer-by-layer;
  • antioxidant;
  • polyphenol;
  • immunomodulatory

Abstract

Though transplantation of pancreatic islet cells has emerged as a promising treatment for Type 1 diabetes its clinical application remains limited due to a number of limitations including both pathogenic innate and adaptive immune responses. This paper reports on a novel type of multifunctional cytoprotective material applied to coat living pancreatic islets. The coating utilizes hydrogen-bonded interactions of a natural polyphenol (tannic acid) with poly(N-vinylpyrrolidone) deposited on the islet surface via non-ionic layer-by-layer assembly. It is demonstrated that the coating is conformal over the surface of mammalian islets including those derived from rat, non-human primate (NHP), and human. In contrast to unmodified controls, the coated islets maintain their viability and β-cell functionality for at least 96 hours in vitro. It is also determined that the coating demonstrates immunomodulatory cytoprotective properties suppressing pro-inflammatory cytokine synthesis in stimulated bone marrow-derived macrophages and diabetogenic BDC-2.5 T cells. The coating material combines high chemical stability under physiologically relevant conditions with capability of suppressing cytokine synthesis, crucial parameters for prolonged islet integrity, viability, and function in vivo. This study offers new opportunities in the area of advanced multifunctional materials to be used for a cell-based transplantation therapy