Carbohydr Polym 2025 Nov 01;373:124653. doi: 10.1016/j.carbpol.2025.124653.

A two-birds-with-one-stone polysaccharide-based microneedle therapy: Prolonged glycemic regulation and accelerated diabetic wound healing.

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Microneedle-based delivery systems represent an advanced strategy for painless, minimally invasive transdermal insulin therapy in diabetes. Despite their potential, the clinical translation of microneedle platforms is impeded by critical challenges, including immunogenic reactions triggered by residual materials in the skin, limited durations of insulin release, and the lack of glucose-lowering-driven therapeutic frameworks for diabetic wound healing. Here, we propose a dual-functional therapeutic strategy through synergistic modification of glycol chitosan and dextran polysaccharides to engineer a biomimetic pancreatic insulin delivery platform. This innovative design integrates boronate ester bonds to enable glucose-responsive release while utilizing imine bonds to simultaneously enhance hydrogel stability and precisely modulate insulin release kinetics. Inspired by starfish morphology, microneedle design and array configuration are optimized, achieving a 6.13-fold increase in skin adhesion. In vivo, a single patch maintains normoglycemia for 71.6 h (>96 % mass retention), accelerates wound closure (10 mm wound healed by day 12), and sustains glycemic control for 14 days. This work developed a glucose-responsive, bioinspired islet-mimetic microneedle system capable of dynamically modulating insulin release flux for dual glycemic control and wound healing in diabetes management.

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