Programmable Self-Heating Microneedle Patch for on-Demand Postprandial Glucose Management.

Achieving on-demand glucose control to prevent postprandial spikes remains a significant challenge in diabetes management. Here, we present a programmable self-heating microneedle (PSH-MN) patch for on-demand, timed‑sequence insulin delivery. The patch features a three-dimensional‌ (3D)-printed backing with four quadrants, each with a calcium oxide (CaO)-based exothermic mixture and a water capsule. MN tips made of polyvinylpyrrolidone (PVP) for insulin loading are spray-coated with a phase-change material (PCM), forming a thermosensitive barrier for controlled, sequential release. The patch possesses sufficient mechanical strength for skin penetration (>760 µm) and maintains good stability for long-term storage (>3 months). Mechanical activation of a quadrant triggers a rapid self-heating exothermic reaction (∼80°C within 1 min) that melts the coating, accelerates PVP dissolution, and enables on-demand insulin release. In vitro studies confirm programmable, sequential drug release with spatial control and linear dose‑response. After systematic biosafety validation, the activated patch lowers blood glucose to normal levels within 2 h and sustains it for over 3 h in a diabetic rat model. Sequential quadrant activation in glucose tolerance tests successfully counteracts four consecutive meal-mimicking spikes within 24 h. This PSH-MN patch offers a robust, biosafe, and user-friendly platform for programmable insulin delivery, providing a promising approach for personalized diabetes management.