Promoting Dendrimer Self-Assembly Enhances Covalent Layer-by-Layer Encapsulation of Pancreatic Islets

For type 1 diabetics, islet transplantation can induce beneficial outcomes, including insulin independence and improved glycemic control. The long-term function of the grafted tissue, however, is challenged by host inflammatory and immune responses. Cell encapsulation can decrease detrimental host responses to the foreign implant, but standard microencapsulation imparts large transplant volumes and impaired metabolite and nutrient diffusion. To mitigate these effects, we developed an efficient covalent Layer-by-Layer (cLbL) approach for live-cell nanoencapsulation, based on oppositely charged hyperbranched polymers functionalized with complementary Staudinger ligation groups. Reliance on cationic polymers for cLbL, however, is problematic due to their poor biocompatibility. Herein, we incorporated the additional feature of supramolecular self-assembly of the dendritic polymers to enhance layer uniformity and decrease net polymer charge. Functionalization of poly (amino amide) (PAMAM) with triethoxysilane decreased polymer charge without compromising the uniformity and stability of resulting nanoscale islet coatings. Encapsulated pancreatic rat islets were viable and functional. The implantation of cLbL islets into diabetic mice resulted in stable normoglycemia, at equivalent dosage and efficiency as uncoated islets, with no observable alterations in cellular engraftment or foreign body responses. By balancing multi-functionality and self-assembly, nano-scale and stable covalent layer-by-layer polymeric coatings could be efficiently generated onto cellular organoids, presenting a highly adaptable platform for broad use in cellular transplantation.