Pancreatic β 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 β cell spheroids for the islet transplantation application. The cytoprotective effect against physical stress and the immune protective effect were evaluated. Last, caged mouse β 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.
Bibliographical noteFunding Information:
This research was financially supported by the Ministry of Science and ICT (NRF-2016R1E1A1A01943393, NRF-2017M3A9C6031786, NRF-2019M3A9G1023840, NRF-2019R1I1A1A01059554, NRF-2019M3A9H1103786, and NRF-2020R1A2C3005834). This research was supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (HI18C0453). The Institute of Engineering Research at Seoul National University provided research facilities for this work. This work is also financially supported by the LG Chemical Global Innovation Grant.
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