Selenium nanozyme-crosslinked composite hydrogel for promoting cartilage regeneration in osteoarthritis via an integrated ‘outside-in’ and ‘inside-out’ strategy

作者：Wenyan Gao, Shaochun Li, Ya Miao, Guangfu Yuan, Gaoyang Li, Guoqiang Zhou, Guang Jia, Xinjian Yang, Yi Jin · 发表于：Journal of Colloid and Interface Science · 年份：2025 · DOI：10.1016/j.jcis.2025.137612 · 被引用次数：10 · 研究领域：Osteoarthritis Treatment and Mechanisms、Advanced Nanomaterials in Catalysis、Nanoplatforms for cancer theranostics

Osteoarthritis (OA), a degenerative joint disease, is characterized by chondrocyte senescence, extracellular matrix (ECM) degradation, and chronic inflammation, with limited regenerative capacity. Current therapies primarily provide symptom relief, therefore highlighting the need for more effective strategies to address OA's multifactorial pathology. This study introduces an innovative selenium nanozyme-crosslinked injectable composite hydrogel (Se/PRP-OGel), which combines selenium nanoparticles (SeNPs) with platelet-rich plasma (PRP) in a biocompatible oxidized chondroitin sulfate-gelatin scaffold (OGel), to address OA through an integrated "outside-in" and "inside-out" strategy. The "outside-in" strategy utilizes SeNPs to scavenge reactive oxygen species (ROS), alleviate oxidative stress, and restore redox balance, thereby reducing extracellular damage and modulating inflammation in the OA microenvironment. Concurrently, the "inside-out" strategy utilizes PRP's bioactive growth factors (e.g., TGF-β, IGF, FGF) to rejuvenate senescent chondrocytes, stimulate proliferation, and enhance ECM synthesis, creating a regenerative microenvironment. The results showed that Se/PRP-OGel demonstrated excellent biocompatibility, reduced ROS levels, mitigated chondrocyte senescence, and balanced ECM homeostasis. Moreover, it promoted cartilage repair, pain relief, and functional restoration in an OA rat model. This dual approach interrupts OA's degenerative cycle and fosters cartilage reg...