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Osteoarthritis (OA) is a common chronic inflammatory disease in the joints. It is one of the leading causes of disability with increasing morbidity, which has become one of the serious clinical issues. Current treatments would only provide temporary relief due to the lack of early diagnosis and effective therapy, and thus the replacement of joints may be needed when the OA deteriorates. Although the intra‐articular injection and oral administration of drugs are helpful for OA treatment, they are suffering from systemic toxicity, short retention time in joint, and insufficient bioavailability. Nanomedicine is potential to improve the drug delivery efficiency and targeting ability. In this focused progress review, the particle‐based drug loading systems that can achieve targeted and triggered release are summarized. Stimuli‐responsive nanocarriers that are sensitive to endogenous microenvironmental signals such as reactive oxygen species, enzymes, pH, and temperature, as well as external stimuli such as light for OA therapy are introduced in this review. Furthermore, the nanocarriers associated with targeted therapy and imaging for OA treatment are summarized. The potential applications of nanotherapies for OA treatment are finally discussed.

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The modulation of inflammation in tissue microenvironment takes an important role in cartilage repair and regeneration. In this study, a novel hybrid scaffold was designed and fabricated by filling a reactive oxygen species (ROS)-scavenging hydrogel (RS Gel) into a radially oriented poly(lactide-co-glycolide) (PLGA) scaffold. The radially oriented PLGA scaffolds were fabricated through a temperature gradient-guided phase separation and freeze-drying method. The RS Gel was formed by crosslinking the mixture of ROS-responsive hyperbranched polymers and biocompatible methacrylated hyaluronic acid (HA-MA). The hybrid scaffolds exhibited a proper compressive modulus, good ROS-scavenging capability, and cell compatibility. In vivo tests showed that the hybrid scaffolds significantly regulated inflammation and promoted regeneration of hyaline cartilage after they were implanted into full-thickness cartilage defects in rabbits for 12 w. In comparison with the PLGA scaffolds, the neo-cartilage in the hybrid scaffolds group possessed more deposition of glycosaminoglycans and collagen type II, and were well integrated with the surrounding tissue.