Nanozyme-Reinforced miR-197-3p Delivery Resets Metabolic and Senescence Pathways to Rejuvenate Osteoarthritic...

Area of Science:

• Biomedical Engineering
• Regenerative Medicine
• Molecular Biology

Background:

• Osteoarthritis (OA) is a degenerative joint disease characterized by oxidative stress, chondrocyte senescence, and extracellular matrix (ECM) degradation.
• Current OA treatments lack disease-modifying capabilities, highlighting the need for novel therapeutic strategies.

Purpose of the Study:

• To identify novel therapeutic targets for osteoarthritis.
• To develop an effective intra-articular delivery system for therapeutic microRNAs and antioxidants.

Main Methods:

• Identified miR-197-3p as a downregulated, cartilage-protective microRNA in aged and osteoarthritic cartilage.
• Engineered a multifunctional microsphere platform (miR/PBNP@Gel) co-encapsulating miR-197-3p and Prussian blue nanozymes (PBNPs) in GelMA hydrogel.
• Evaluated the therapeutic efficacy of miR/PBNP@Gel in vitro and in vivo OA models, including metabolomic profiling.

Main Results:

• miR-197-3p was found to restore ECM anabolism, suppress senescence, and target G3BP1.
• The miR/PBNP@Gel platform enhanced miRNA stability, cellular uptake, and provided continuous reactive oxygen species (ROS) scavenging.
• Treatment with miR/PBNP@Gel reversed chondrocyte dysfunction and senescence, promoted cartilage repair, and improved joint function in vivo.
• Metabolomic analysis revealed reprogramming of the TCA cycle and antioxidant pathways.

Conclusions:

• miR-197-3p is a novel therapeutic regulator for osteoarthritis.
• The injectable, cell-free miR/PBNP@Gel strategy effectively combines miRNA therapy and redox modulation for OA disease modification and cartilage regeneration.