Acid-responsive MgB₂ thick nanosheets MBNs alleviate knee osteoarthritis by dual delivery of H₂ and Mg2+

Acid-responsive thick nanosheets for knee osteoarthritis therapy. • Dual delivery of H₂ gas and Mg 2+ ions in inflammatory joints. • H₂ scavenges ROS and reduces pro-inflammatory cytokines. • Mg 2+ contributes to chondroprotection and cartilage matrix maintenance. • A gas-ion synergistic strategy to reprogram the joint microenvironment. The inadequacy of current Knee Osteoarthritis (KOA) therapies lies in the challenges of effectively overcoming oxidative stress and repairing damaged joint cartilage. To address these challenges, we developed an innovative “gas-ion synergistic delivery” treatment strategy using two-dimensional magnesium boride thick nanosheets (MBNs). The MBNs, prepared via solvent-assisted exfoliation, continuously release hydrogen gas (H₂) and magnesium ions (Mg 2+ ) in the mildly acidic microenvironment of KOA (pH 6.5), providing a dual therapeutic effect. Hydrogen shows strong antioxidant properties, effectively scavenging free radicals 2,2-azino -bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH)), reducing intracellular ROS levels. Furthermore, MBNs significantly suppress the expression of pro-inflammatory cytokines IL-1β and TNF-α. This strategy leverages “gas antioxidation-ion regeneration” dual-mode synergy, offering low cost and exceptional biocompatibility. It presents an innovative solution with clear translational potential for microenvironment reprogramming and targeted therapy of KOA.