A Blood-Triggered Adhesive Hydrogel Loaded with Reactive Oxygen Species-Responsive Liposomes for the Treatment of Acute Kidney Injury

Partial nephrectomy (PN) is the standard treatment for renal tumors but is frequently complicated by acute kidney injury arising from two distinct pathological insults: the ischemia-reperfusion injury induced by vascular clamping and the mechanical trauma caused by parenchymal suturing. Conventional hemostatic suturing often exacerbates tissue necrosis via high tension, while IRI triggers oxidative bursts and ferroptosis. To overcome these synergistic challenges, a blood-triggered, dual-cross-linked adhesive hydrogel loaded with reactive oxygen species-responsive (ROS-responsive) GW7647 liposomes was engineered. Upon contact with the bleeding surface, the hydrogel rapidly solidified to achieve effective hemostasis, acting as a tension-free sealant to replace or reduce suturing. Concurrently, the elevated reactive oxygen species (ROS) levels in the ischemic microenvironment triggered the phase transition of the embedded liposomes, enabling the on-demand release of GW7647. Mechanistically, GW7647 activated the PPARα/Nrf2/GPX4-SLC7A11 signaling axis, effectively suppressing lipid peroxidation and blocking ferroptosis. By integrating rapid, noncompressive hemostasis with stress-adaptive metabolic regulation, this multifunctional platform promoted tissue regeneration and functional recovery, offering a promising therapeutic strategy for post-PN management.