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Papers of the Week


Papers: 25 Jan 2025 - 31 Jan 2025


2025 Jan 27


J Control Release


39880042

ROS fueled autonomous sol-gel-sol transitions for on-demand modulation of inflammation in osteoarthritis.

Authors

Chen Y, Yin N, Jin S, Yang L, He Y, Guo L, Feng M

Abstract

Osteoarthritis is the most prevalent form of arthritis, and a leading cause of pain and long-term disability. Dysregulation of redox homeostasis is a key feature in the pathological progression of osteoarthritis that amplifies the inflammatory response, aggravates synovitis and accelerates cartilage degradation. Herein, a hemin and chitosan-mediated antioxidant gel inducing ROS conversion (hc-MAGIC) was constructed to targeting oxidative stress for osteoarthritis treatment. The optimized hc-MAGIC exhibited autonomous sol-gel-sol transition properties, which enable to be administered via intra-articular injections, prolong retention in the joint cavity, and controlled modulation of inflammation in response to ROS. Notably, with extracellular ROS fueled, hc-MAGIC could address hypoxia in the osteoarthritic joint cavity through spatiotemporally controlled generation of oxygen (O). Moreover, hc-MAGIC restored the impaired antioxidative capacity of macrophages by upregulating HO-1 on demand, resulting in suppressing excessive intracellular ROS generation. Consequently, by restoring both extracellular and intracellular redox homeostasis in osteoarthritic joints, hc-MAGIC markedly reversed the inflammatory microenvironment to support chondrogenesis, prevented cartilage degradation, and promoted cartilage repair by augmenting cartilage matrix formation. Therefore, featuring its sol-gel-sol transition properties,ROS-to-O conversion, and dual-mode redox regulation, hc-MAGIC offers a potent novel therapy for on-demand modulation of inflammation in osteoarthritis.