A Piezo-Mimetic Ionic Hydrogel Harnessing Joint Motion for Cartilage Repair

Articular cartilage regeneration remains challenging due to its avascular architecture and limited intrinsic repair capacity. Here, we present a piezo-mimetic ionic hydrogel (PSG-Mg_c) that harnesses endogenous joint motion to orchestrate cartilage repair through mechano-electrical coupling. The hydrogel integrates a freeze-thaw crosslinked poly(vinyl alcohol) (PVA) backbone for mechanical resilience with sodium alginate (SA) and carboxyl-enriched acylated gelatin (Acy-Gel) to construct a hydrated, ion-permissive network capable of dynamic Mg²⁺ coordination. Unlike conventional electron-based piezoelectric materials, PSG-Mg_c transduces mechanical deformation into localized ionic currents via deformation-induced asymmetric ion migration, while simultaneously enabling sustained Mg²⁺ delivery to modulate cellular metabolism. This dual mechano-electrical coupling and biochemical regulation enhance chondrocyte activity and promote extracellular matrix synthesis in vitro. In anatomically distinct trochlear and femoral condylar defect models, the hydrogel exhibits load-adaptive functionality, generating amplified bioelectric cues under higher mechanical stress and achieving near-native cartilage restoration. By coupling mechanical energy harvesting with ion-mediated electrochemical signaling, PSG-Mg_c establishes a new paradigm that shifts cartilage repair from passive scaffolding toward active mechano-electrical coupling regeneration.