Skin-mimetic albumin hydrogel as an artificial protein skin with a mitochondria-targeted bioenzymatic cascade for cross-scale redox repair in diabetic wounds

Artificial skin substitutes and hydrogel dressings have improved diabetic wound care by providing coverage, moist interfaces, and structural support for re-epithelialization. However, many current systems still show limited long-term retention and insufficient active remodeling of the hostile diabetic wound microenvironment, where ROS-driven oxidative stress serves as a key node sustaining chronic nonhealing. Here, we report BTSC, a dynamic skin-mimetic albumin hydrogel designed as a wound-retentive artificial protein skin with an embedded mitochondria-targeted bioenzymatic cascade module for cross-scale redox repair. The albumin network acts as a bioactive protein matrix rather than a passive scaffold, integrating injectability, self-healing, wet adhesion, skin-like mechanical compatibility, tissue-level ROS buffering, and stabilization of mitochondria-targeted SOD/CAT nanocomposites (TPP-SC). In the acidic diabetic wound microenvironment, Schiff base crosslinks enabled sustained pH-responsive TPP-SC release over approximately one week. During local retention, BTSC buffered wound-bed ROS and supported SOD/CAT-mediated O 2 generation from endogenous H 2 O 2 , mitigating oxidative and hypoxic stress. Released TPP-SC further accumulated in mitochondria, attenuated mtROS, and helped restore mitochondrial redox balance. This tissue-to-organelle redox regulation reduced inflammation, promoted angiogenesis, collagen remodeling, and re-epithelialization, and accelerated diabetic wound closure.