In situ-built chemo-electroactive hydrogel incorporating Mg-based hydrogen generators for osteoarthritis therapy

As a degenerative disease, osteoarthritis (OA) is critically influenced by inflammation and extracellular matrix (ECM) degradation in the repair of articular cartilage. Though the in-situ hydrogel could alleviate joint pain with high patient compliance, the synergetic management of the pathological progression of osteoarthritis is limited. Herein, a microenvironment-responsive chemo-electroactive hydrogel is designed by integrating asymmetric magnesium hydrogen generators (MHG) and black phosphorus nanosheets (BPNS) within a biomimetic double-network matrix (PHO) for cartilage repair. The MHG and BPNS couple to form a micro-galvanic cell, where MHG provides electrons and BPNS acts as a low-impedance heterogeneous cathode, establishing a stable microcurrent field. The biomimetic double-network not only provides PHO-MHG@BP with excellent injectability and self-healing ability, but also triggers intelligent release of H₂ and Mg²⁺ under the acidic conditions typical of osteoarthritis. This facilitates scavenging ROS and restoring the inflammatory microenvironment. Simultaneously, the PHO-MHG@BP hydrogel facilitates localized microcurrent transmission through an in situ micro-galvanic cell reaction, achieving long-term bioelectrical regulation for chondrocyte proliferation via the CaMKII signaling cascade. These results demonstrate that the chemo-electroactive hydrogel not only restores redox and bioelectrical homeostasis but also modulates the OA microenvironment, providing a comprehensive therapeutic strategy for osteoarthritis.