Cold‐Responsive Nanocapsules Enable the Sole‐Cryoprotectant‐Trehalose Cryopreservation of β Cell–Laden Hydrogels for Diabetes Treatment

Abstract Islet transplantation has been one promising strategy in diabetes treatment, which can maintain patient's insulin level long‐term and avoid periodical insulin injections. However, donor shortage and temporal mismatch between donors and recipients has limited its widespread use. Therefore, searching for islet substitutes and developing efficient cryopreservation technology (providing potential islet bank for transplantation on demand) is in great need. Herein, a novel cryopreservation method is developed for islet β cells by combining microfluidic encapsulation and cold‐responsive nanocapsules (CR‐NCs). The cryopreserved cell‐laden hydrogels (calcium alginate hydrogel, CAH) can be transplanted for diabetes treatment. During the freezing process, trehalose is released inside β cells through the CR‐NCs and serves as the sole cryoprotectant (CPA). Additionally, CAH helps cells to survive the freeze–thaw process and provide cells with a natural immune barrier in vivo. Different from traditional cryopreservation methods, this method combining the CR‐NCs and hydrogel encapsulation replaces the toxic CPAs with natural trehalose. Great preservation results are obtained and transplantation experiments of diabetic rats further prove the excellent glucose regulation ability of such β cell–laden hydrogels post cryopreservation. This novel cryopreservation method helps to establish a reliable and ready‐to‐use bank of biological samples for transplantation therapy and other biomedical applications.