Wharton's jelly (WJ) is considered a potential scaffold in tissue‐engineered trachea for its similar composition and function to cartilage tissue. However, the feasibility of using WJ to construct engineered neocartilage tissue has not been reported, let alone tubular tracheal cartilage regeneration and segmental tracheal lesion repair. Here, electrospun nanofibrous membranes composed of three different decellularized WJ matrix (DWJM)/poly(ε‐caprolactone) (PCL) ratios (8:2, 5:5, and 2:8) are fabricated. The results demonstrate improved degradation speed, absorption, and cell adhesion capacity but weakened mechanical properties with increased DWJM content, but satisfactory homogeneous cartilage regeneration is only achieved in the DWJM/PCL (8:2) group after 12 weeks in vivo culture. Furthermore, homogeneous, 3D, tubular, trachea‐shaped cartilage is constructed with a controllable lumen diameter and wall thickness based on the 2D nanofibrous membrane using a modified sandwich model, in which the chondrocyte‐membrane construct is rolled around a silicon tube. Most importantly, by combining the above schemes with previously established vascularization and epithelialization techniques, chondrification, vascularization, and epithelialization are achieved simultaneously thus realizing long‐term (6 months) circumferential tracheal lesion repair in a rabbit model with a biological structure and function similar to that of native trachea, representing a promising approach for the clinical application of tracheal tissue engineering.

Skin wound healing strategies that promote sustainable healing, prevent bacterial infections, and cause only mild irritation are urgently needed for open wound therapy. In this study, a system that consists of a reactive oxygen species (ROS)‐degradable hydrogel dressing, with encapsulated biosafe nitric oxide (NO) donor L‐arginine (L‐Arg), and a low level (100 × 10−6 m) of the household disinfectant hydrogen peroxide (H2O2) is established for sustainable wound therapy and disinfection. Under stimulation with a low level of H2O2, NO is sustainably generated from L‐Arg within the hydrogel dressing, which mediates macrophage and fibroblast chemotaxis to the wound site, as well as collagen synthesis, resulting in rapid wound healing and skin organ regeneration. The combination of H2O2 and NO also endows the system with a synergistic antibacterial ability to eliminate ampicillin‐resistant Escherichia coli. In addition, a full‐thickness skin wound model demonstrates that the ROS‐degradable hydrogel dressing, with a wound exudate adsorption ability, shows effective wound healing promotion and a good biocompatibility, without any hazardous residues and skin irritation. This ROS‐responsive, degradable, synergistic wound healing system provides an alternative strategy for sustainable wound treatment, both at home and in the clinic.

Nanozyme catalytic therapy triggered by tumor‐specific endogenous stimuli is an emerging tumor therapy that attracts wide attention. However, the current therapeutic efficacy of nanozyme catalytic therapy is severely limited by the catalytic efficiency of nanozymes and the concentration of endogenous reaction substrates. Herein, a novel and efficient IrN5 single‐atom (IrN5 SA) nanozyme is developed with multiple enzyme‐like catalytic activities. Due to the synergistic effect of central Ir single‐atom and axial N coordination, IrN5 SA exhibits better enzymatic catalytic performance than IrN4 SA. At tumor sites, IrN5 SA can generate a large amount of reactive oxygen species (ROS) through oxidase (OXD)‐like and peroxidase (POD)‐like catalytic activities. Moreover, IrN5 SA can also generate O2 and hydrogen peroxide (H2O2) through catalase (CAT)‐like and nicotinamide adenine dinucleotide (NADH) oxidase (NOX)‐like catalytic activities, realizing the efficient nanozyme catalytic therapy in a substrate‐cycle manner. Additionally, IrN5 SA can effectively break the intracellular NADH/NAD+ cycle balance by mimicking NOX, and then cooperate with fatty acid synthase cerulenin (Cer) to interfere with the energy metabolism homeostasis of tumor cells. Consequently, the designed IrN5 SA/Cer nanoagent can disrupt redox and metabolic homeostasis in the tumor region through an enzyme‐mimicking cascade reaction, effectively overcoming the shortcomings of current nanozyme catalytic therapy.