(521e) A Balanced Charged Immune-Evasive Hydrogel for Rapid and Long-Term Glycemic Regulation in T1DM Mice

Type 1 diabetes mellitus (T1DM) is a chronic epidemic caused by permanent destruction of insulin-producing β cells and results in absolute insulin deficiency, afflicting over 30 million people worldwide. Transplantation of encapsulated islets is a promising treatment for patients with T1DM. However, its long-term clinical therapeutic efficacy is still hindered by the foreign body reaction (FBR), which will seriously block the mass/signal transport between the implants and the body. Herein, we develop a balanced charged polyelectrolyte hydrogel by tuning the ratio between negatively charged alginate and positively charged poly (ethylene imine) (PEI). The prepared Alg/PEI hydrogel is neutrally charged and can effectively resist the adhesion of proteins, cells, and bacteria. We further use this hydrogel as an immunocamouflage material for islet transplantation therapy. It is found that the encapsulated islets can maintain their glucose-responsive and insulin-producing functions. Additionally, the hydrogel can also effectively evade in vivo FBR after intraperitoneal implantation in an immunocompetent streptozotocin-induced diabetic mouse model. As a result, 100% of the mice rapidly recover to normoglycemia within 2 d and stably maintain for at least 150 d without any immunosuppression treatment. These findings shed light on the “insulin independence and immunoisolation” encapsulation strategy, which can overcome the barrier of islet transplantation and holds the potential to improve current clinical therapeutic efficacy.