Human donor islets coated with functionalized chitosan and alginate nanoscale layers can restore normoglycemia in diabetic mice

Conformal coating is a promising encapsulation approach to reduce the immunogenicity of islet transplants in the treatment of type 1 diabetes (T1D). The primary objective of this work was to investigate a combination of non-immunogenic polyelectrolytes, tetrahydropyran triazole phenyl-alginate (TZ-AL) and quaternized phosphocholine-chitosan (PC-QCH), to create a nano-thin film onto the surface of human donor islets and assess its potential for clinical translation. To evaluate the coating materials, spheroids made from human-derived proliferative EndoC-βH1 and non-proliferative βH5 beta cell lines as pseudo-islet models was used as complementary models before applying the coating onto human islets. Coating formation and biocompatibility were first validated with spheroids and then applied to human islets. The results indicated formation of the desired coating morphology on both spheroids and human islets. In addition, both coated spheroids and human islets cultured for 7 days <i>in vitro</i> maintained cell viability, metabolic activity, and glucose stimulated insulin secretion compared to non-coated control groups. Gene expression of islet/beta cell markers (<i>INS</i>, <i>GCG</i>, <i>PDX1</i>, and <i>MAFA)</i> also remained similar, suggesting no significant impact on coated spheroid and islet cell function. Lastly, transplantation of coated human islets in diabetic mice restored normoglycemia for up to 30 days. These findings suggest that this conformal coating can maintain human islet cell function and thus, it can be a promising candidate towards clinical application of nanoencapsulation for T1D cell therapy.