β-Diketone Functionalized Microspheres Chelate Reactive Iron via Metal Coordination for Cartilage Repair

Area of Science:

• Biomaterials Science
• Biomedical Engineering
• Cell Biology

Background:

• Excessive intracellular iron accumulation causes mitochondrial dysfunction and chondrocyte ferroptosis, contributing to osteoarthritis (OA) cartilage damage.
• Ferroptosis, an iron-dependent cell death, is a critical factor in the pathogenesis of OA.

Purpose of the Study:

• To develop and evaluate micelle-microfluidic hydrogel microspheres for in situ reactive iron removal.
• To investigate the potential of these microspheres in restoring mitochondrial homeostasis and treating OA by inhibiting chondrocyte ferroptosis.

Main Methods:

• Fabrication of hydrogel microspheres with stimuli-responsive β-diketone groups for iron chelation.
• Assessment of microsphere efficacy in reducing iron influx (TfR1 downregulation) and mitochondrial iron uptake (CISD1 upregulation).
• Evaluation of the antioxidant effects on the Nrf2/SLC7A11/GPX4 axis to inhibit ferroptosis.

Main Results:

• The hydrogel microspheres effectively chelated intracellular reactive iron, restoring mitochondrial iron homeostasis.
• Microspheres reduced iron influx and mitochondrial uptake by modulating TfR1 and CISD1 expression.
• Antioxidant properties mitigated chondrocyte ferroptosis, slowing OA progression.

Conclusions:

• The developed hydrogel microspheres offer a promising minimally invasive therapeutic strategy for OA by sustainably chelating reactive iron.
• This system demonstrates potential for treating ferroptosis-mediated diseases through targeted intracellular iron management.