Glucose and H2O2-responsive G-quadruplex smart hydrogel for dual control of hyperglycemia and diabetic wound management

Abstract

Chronic diabetes and diabetes-related wounds are major health concerns worldwide. Generally, type-1 diabetes and advanced type-2 diabetes are diagnosed with externally administered insulin. Additionally, traditional wound dressings are often ineffective to combat diabetic wounds. Here, we focus on developing a stimuli-responsive thixotropic hydrogel based on guanosine (G) and 2,4,6-trifluorophenylboronic acid (FBA) to enable efficient insulin delivery and to manage diabetic wounds. The hydrogel has been well characterized by various analytical techniques such as thioflavin T binding assay, CD spectroscopy, PXRD, 11B VT-NMR and FT-IR spectroscopy. Furthermore, the hydrogel's morphology and mechanical properties have been investigated using FE-SEM, AFM, HR-TEM and rheometer respectively. Live/dead staining, MTT and hemolysis assays collectively indicate that the hydrogel is biocompatible enabling the scope of further in vivo studies. Insulin and berberine-loaded hydrogel have markedly accelerated diabetic wound contraction and almost complete restoration of epidermal and dermal architecture achieved by 21 days, depicting its strong regenerative efficacy in an in vivo diabetic wound model. The insulin-loaded hydrogel has achieved sustained glycemic control up to 96 h that is markedly superior to conventional insulin injections in diabetic rats. Overall, these findings establish that the hydrogel is a dual-function therapeutic system for next-generation diabetic wound therapy and insulin delivery. © 2026 Elsevier B.V.