Urine‐Microenvironment‐Initiated Composite Hydrogel Patch Reconfiguration Propels Scarless Memory Repair and Reinvigoration of the Urethra

Abstract The harsh urine microenvironment (UME), as an inherent hurdle, endangers and renders urethral repair unreachable. Innovatively, the unfavorable UME is utilized as the design source to construct a UME‐responsive 3D‐printed hydrogel patch for realizing scarless memory repair, wherein laser‐excited reactive oxygen species (ROS) production and mechanical strength elevation using chemically crosslinked silicon quantum dots are accessible. Intriguingly, the proposed composite scaffolds can respond to Ca²⁺ in urine, cause structure reconfiguration, and repress swelling to further enhance scaffold stiffness. Systematic experiments validate that ROS birth and unexpected stiffness elevation in such UME‐responsive scaffolds can realize scarless memory repair of the urethra in vivo. Comprehensive mechanism explorations uncover that the activations of cell proliferation and collagen‐related genes (e.g., MMP‐1 and COL3A1) and the dampening of fibrosis‐related (e.g., TGF‐β/Smad) and mechanosensitive genes (e.g., YAP/TAZ) are responsible for the scarless memory repair of such UME‐responsive scaffolds via enhancing collagen deposition, recalling mechanical memory, decreasing fibrosis and inflammation, and accelerating angiogenesis. The design rationales (e.g., UME‐initiated structure reconfiguration and antiswelling) can serve as an instructive and general approach for urethra repair.