Electroactive Dressing Induces Piezoelectric Signals and Ca 2 ⁺ Activation to Enhance Osteoblast Differentiation and Bone Regeneration in Negative Pressure Therapy

Abstract Negative‐pressure wound therapy plays a pivotal role in treating open bone fractures. However, the loss of bioelectricity during the healing process significantly delays tissue repair. The generation and maintenance of bioelectric fields require a complex interplay of multiple factors. Previous attempts to regenerate the lost bioelectric field using exogenous conductive materials or supplementing endogenous functional electrolytes have limited success. During this study, a novel electroactive dressing is formulated tailored for negative‐pressure therapy by combining piezoelectric poly L‐lactic acid doped with bioactive glass and amino‐terminated dendritic macromolecules. When subjected to negative pressure, the mechanical deformation of the dressing generates exogenous piezoelectric signals that effectively couple with the endogenous ionic electric fields. Furthermore, the amine‐terminated poly(amidoamine) dendritic macromolecules capture cations via coordination and ion‐exchange mechanisms, thus retaining electrolytes at the wound site. The findings indicate that the bioelectricity generated by the electroactive dressing under negative pressure facilitates the influx of calcium ions into cells. Calcium ions bind calmodulin, activating Ca 2 ⁺/calmodulin‐dependent kinase II, which further activates phosphatidylinositol3‐kinase (PI3K), initiating the PI3K/Akt pathway and enhancing osteoblast activity. The efficacy of the developed electroactive dressing is verified using a critical‐sized cranial bone‐defect model in rats, demonstrating its significant osteogenic differentiation potential. The exogenous and endogenous fields provided by the electroactive dressing maintain the electrophysiological state necessary for bone regeneration, providing a novel therapeutic approach for clinical open fractures.