Novel enzymatic cross-linking-based hydrogel nanofilm caging system on pancreatic β cell spheroid for long-term blood glucose regulation

Pancreatic beta cell therapy for type 1 diabetes is limited by low cell survival rate owing to physical stress and aggressive host immune response. In this study, we demonstrate a multilayer hydrogel nanofilm caging strategy capable of protecting cells from high shear stress and reducing immune response by interfering cell-cell interaction. Hydrogel nanofilm is fabricated by monophenol-modified glycol chitosan and hyaluronic acid that cross-link each other to form a nanothin hydrogel film on the cell surface via tyrosinase-mediated reactions. Furthermore, hydrogel nanofilm formation was conducted on mouse beta cell spheroids for the islet transplantation application. The cytoprotective effect against physical stress and the immune protective effect were evaluated. Last, caged mouse beta cell spheroids were transplanted into the type 1 diabetes mouse model and successfully regulated its blood glucose level. Overall, our enzymatic cross-linking-based hydrogel nanofilm caging method will provide a new platform for clinical applications of cell-based therapies.

Automated summary

This study demonstrates a multilayer hydrogel nanofilm caging strategy to protect pancreatic beta cells from physical stress and reduce immune response. By forming a nanothin hydrogel film on the cell surface, the cytoprotective and immune protective effects were evaluated, showing successful regulation of blood glucose levels in a type 1 diabetes mouse model. Overall, this enzymatic cross-linking-based hydrogel nanofilm caging method provides a new platform for clinical applications of cell-based therapies.