Asymmetric hydrogel with "spear-shield" properties promotes diabetic foot ulcer healing by modulating macrophage...

Diabetic foot ulcer (DFU) remain a formidable clinical challenge, with treatment difficulties stemming from impaired macrophage autophagy within the hyperglycaemic and oxidative stress microenvironment, coupled with the structural and functional limitations of existing dressings. Here, we report an asymmetric "spear-shield" hydrogel dressing designed to overcome these impairments and accelerate DFU repair. The dressing is built on a polyacrylamide (PAM) network incorporating a gradient of copper alginate (Cu-Alg), yielding a structurally continuous yet functionally stratified bilayer: a rigid, highly cross-linked outer shield that provides mechanical protection and anti-adhesion, and a soft, low-cross-linked inner spear that conforms to the wound bed and enables robust tissue adhesion. The spear layer further carries macrophage-targeting liposomes (AP-Lipo) assembled from dimeric artemisinin conjugates (dACS) and phosphatidylserine (PS). Artemisinin and Cu²⁺ activate macrophage autophagy via the PI3K/AKT/mTOR and AMPK/mTOR pathways. Overall, this study demonstrates that an asymmetric hydrogel structure can effectively integrate targeted autophagy reactivation with intelligent wound protection, offering a new strategy for chronic wound therapy.