Mechano-Iontronic Hydrogels Generating Biomimetic Endogenous Bioelectricity for Promoting Cartilage Regeneration

Articular cartilage regeneration has long been a formidable challenge because of its avascular and aneural nature. Traditional approaches, using exogenous electrical stimulation or electroactive materials, often fail to align with the endogenous iontronic bioelectricity of natural cartilage. Herein, an implantable mechano-iontronic hydrogel (MI-hydrogel) is biomimetically designed to enhance cartilage repair. This MI-hydrogel generates iontronic electricity under deformation, closely mimicking the characteristics and mechanisms of natural cartilage. It is demonstrated that the MI-hydrogel synergistically integrates iontronic electricity and mechanical stimulation during physical activity, activating the ion channel protein Piezo1. This activation promotes the chondrogenic differentiation of stem cells in vitro and facilitates cartilage repair in vivo. Additionally, these coupled effects are shown to reprogram the metabolic microenvironment, enhancing glutamine metabolism and accelerating the cartilage regeneration process. This study not only underscores the potential of the MI-hydrogel as a novel therapeutic platform but also introduces a new mechanism for tissue regeneration, paving the way for innovative approaches in regenerative medicine.