A fully biodegradable and self-regulating injectable silk fibroin hydrogel for glucose-responsive insulin delivery

Diabetes is one of the most common chronic diseases with a prevalence of 536.6 million worldwide. Self-regulating insulin delivery systems that mimic the function of the pancreas and respond to glucose levels provide enhanced therapeutic effects for diabetes treatment. Herein, we present an intelligent glucose-responsive injectable hydrogel prepared with silk fibroin (SF) and phenylboronic acid (PBA) via Green Chemistry for minimally invasive and controlled administration of insulin. PBA forms hydrogen bonds with the backbone and functional side groups of SF and serves as the crosslinker to speed up the gelation of SF. Under hyperglycemic conditions, PBA forms boronate ester with glucose which disrupts the crosslinking and leads to the swelling of hydrogel for insulin release. More importantly, the glucose-responsive enzymatic degradation of hydrogel further facilitates the release of insulin under hyperglycemic conditions, which contributes to more precise glycemic control. After 48 h, the insulin released percentage at a glucose level of 5 mg/mL was 1.83 and 1.39 times greater than that of 0 mg/mL and 1 mg/mL groups. After one single subcutaneous injection of insulin-encapsulated hydrogel in T1DM Wistar rats, the blood glucose homeostasis is restored in 2 h and maintained for 2 days. Meanwhile, the hydrogel is fully degraded within 3 days in vivo, indicating the excellent match that has been achieved between its function and degradation kinetics. Such kind of fully biodegradable, self-regulating injectable hydrogel is easy to prepare at a low cost, providing a new intelligent platform for controlled insulin delivery to achieve long-term management of diabetes.