21:T4d9,Characterized by nucleus pulposus (NP) cell senescence and extracellular matrix (ECM) degradation, disc degeneration is a common pathology for various degenerative spinal disorders. To date, effective treatments for disc degeneration are absent. Here, we found that Glutaredoxin3 (GLRX3) is an important redox-regulating molecule associated with NP cell senescence and disc degeneration. Using a hypoxic preconditioning method, we developed GLRX3⁺ mesenchymal stem cell-derived extracellular vehicles (EVs-GLRX3), which enhanced the cellular antioxidant defense, thus preventing reactive oxygen species (ROS) accumulation and senescence cascade expansion in vitro. Further, a disc tissue-like biopolymer-based supramolecular hydrogel, which was injectable, degradable, and ROS-responsive, was proposed to deliver EVs-GLRX3 for treating disc degeneration. Using a rat model of disc degeneration, we demonstrated that the EVs-GLRX3-loaded hydrogel attenuated mitochondrial damage, alleviated the NP senescence state, and restored ECM deposition by modulating the redox homeostasis. Our findings suggested that modulation of redox homeostasis in the disc can rejuvenate NP cell senescence and thus attenuate disc degeneration.22:T4e5,Patients with osteoporotic fractures often require effective fixation and subsequent bone repair. However, currently available materials are often limited functionally, failing to improve this cohort's outcomes. Herein, kaempferol-loaded mesoporous bioactive glass nanoparticles (MBGNs)-doped orthopedic adhesives are prepared to assist osteoporotic fracture fixation and restore dysregulated bone homeostasis, including promoting osteoblast formation while inhibiting osteoclastic bone-resorbing activity to synergistically promote osteoporotic fracture healing. The injectability, reversible adhesiveness and malleable properties endowed the orthopedic adhesives with high flexibility and hemostatic performance to adapt to complex clinical scenarios. Moreover, Ca²⁺ and SiO₄ ^4- ions released from MBGNs can accelerate osteogenesis via the PI3K/AKT pathway, while kaempferol mediated osteoclastogenesis inhibition and can slow down the bone resorption process through NF-κB pathway, which regulated bone regeneration and remodeling. Importantly, implementing the orthopedic adhesive is validated as an effective closed-loop management approach in restoring the dysregulated bone homeostasis of osteoporotic fractures.

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