Chitosan-based injectable hydrogels with dual glucose sensors for precise control of insulin release and diabetes mellitus therapy

Chitosan-based injectable hydrogels were designed and fabricated through the dynamic crosslinking of dualreversible covalent bonds (imine and phenylboronate ester) for precise insulin release. The hydrogels contain dual glucose-sensors/responsive elements, featuring high sensitivity and rapid responsiveness to glucose level variation in cumulative and half-hourly pulsed insulin release. The hydrogels demonstrated improved cytocompatibility against HSF cells and histological long-term analysis of tissue after implantation. Evaluation of the glycemic control ability in STZ-induced hyperglycemic mice revealed that the hydrogel system showed excellent glycemic control ability in the glucose tolerance test and maintained blood glucose levels in a normal range for up to 11 days after a single administration. Thus, the hydrogel system showed applicable potential in insulin replacement therapy for diabetes mellitus.