Transplantation of pancreatic islets (cell clusters) has emerged as a promising treatment for Type 1 diabetes.  However its clinical application remains limited due to adverse effects of immunosuppression which puts increase demand for efficient islet coating that can preserve islet viability and function.  We developed an ultrathin polymer coating with immunomodulatory and anti-inflammatory responses to protect living pancreatic islets. The coating was comprised of cytocompatible polymers of hydrogen-bonded natural polyphenol (tannic acid) and poly(N-vinylpyrrolidone) deposited on the islet surface via non-ionic layer-by-layer assembly.  The coating was conformal over the surfaces of rat, non-human primate, and human islets. In contrast to unmodified controls, the coated islets maintained their viability and �-cell functionality for at least 96 hours in vitro.  We also determined that the coating demonstrated immunomodulatory cytoprotective properties suppressing pro-inflammatory cytokine synthesis in stimulated bone marrow-derived macrophages and diabetogenic CD4+ T cells.  A decrease in Th1 cytokine responses was observed when antigen-stimulated BDC-2.5 T cells and LPS-stimulated bone marrow-derived macrophages were co-treated with the coating material, suggesting the efficacy of this encapsulation strategy to provide physical islet protection and prevent efficient autoreactive T cell responses.   The developed material combines high chemical stability under physiologically relevant conditions with capability of scavenging free-radicals, two crucial parameters for prolonged islet integrity, viability, and function in vitro/in vivo.    Our study offers new opportunities in the area of advanced transplant materials to be used in Type 1 diabetes treatment as well as in various areas of cell-based therapy.

Immunomodulatory ultrathin polymer coatings for pancreatic islet modification

246th National Meeting (2013)

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