Breaking the vicious cycle of diabetic wounds with an exosome-engineered dual-responsive microneedle patch

Diabetic wound (DW), a prevalent type of chronic non-healing injury, poses substantial clinical challenges owing to persistent oxidative stress, dysregulated inflammation and recurrent bacterial infections. To rationally modulate the microenvironment of DWs, this study fabricated a core-shell structured multifunctional microneedle (MN) patch, designated as AEP-GCMN. Specifically, we designed engineered exosomes, Aloe-Exo PC (AEP), by encapsulating proanthocyanidins (PC) into aloe-derived exosomes, which were then integrated into methacrylated hyaluronic acid (HAMA) to serve as the core layer of the MN patch. In contrast, a polyvinyl alcohol/polyvinylpyrrolidone (PVA/PVP) blend was loaded with catalase (CAT) and surface-functionalized with Gold Nano-Stars (GNS), forming the structural shell of the patch. The AEP-GCMN patch operates through a multi-stage mechanism: its casing rapidly produces oxygen via CAT upon wound contact, while the embedded GNS enable photothermal antibacterial therapy under NIR light. Subsequently, the sustained release of AEP leads to the intracellular delivery of PCs, which alleviate oxidative stress and inhibit inflammation to improve the microenvironment. Additionally, Aloe-Exos contribute to angiogenesis and cell migration. This intelligent responsive system offers a synergistic strategy for the temporal modulation of hypoxia, infection and chronic inflammation in DWs, representing a promising intelligent therapeutic approach for DW management. ToC figure Proposed multi-mechanistic actions of AEP-GCMN in DW therapy: anti-inflammatory, pro-angiogenic, antibacterial, and overall wound-healing promotion. • A core-shell microneedle patch is engineered for intelligent microenvironment-responsive therapy of diabetic wounds. • The catalytic shell rapidly decomposes H 2 O 2 to generate oxygen, alleviating wound hypoxia upon application. • The bilayer design achieves spatiotemporally regulated sequential release of multiple therapeutic agents. • Engineered plant-derived exosomes actively suppress inflammation, oxidative stress and ferroptosis. • Gold nanostars mediate potent near-infrared photothermal antibacterial activity and immunomodulation.