Exercise-mimetic electrical stimulation of muscles triggered by sonopiezoelectric therapy promotes functional repair of abdominal wall defects

Current clinical approaches for abdominal wall defects (AWD) caused by extensive myofascial tissue loss employ synthetic meshes for fibrotic tissue repair, but fail to restore complete functionality. Under physiological conditions, rhythmic contractions of abdominal wall muscles during respiration generate endogenous bioelectric cues essential for muscle action potentials and cellular behavior. Therefore, we aimed to develop an exercise-mimetic electrical stimulation (ES) triggered by sonopiezoelectric therapy (SPT) to promote functional repair of AWD. To achieve this, a sandwich-like piezoelectric patch (PCP) was fabricated by sandwiching a chitin mat between two polycaprolactone mats. The three-layer structure mimics lateral abdominal muscle microarchitecture and provides topographical cues for myoblast alignment and fusion. Under respiratory-induced mechanical deformation, the PCP patches generate ES, helping restore local electric field homeostasis. Additionally, low-intensity pulsed ultrasound (LIPUS) can be applied to deliver more precise and intensified stimulation, further promoting myogenic differentiation and myoblast fusion in both in vitro and in vivo studies. It was found that ES could activate the Ca 2+ /CaN/NFAT2 signaling pathway under dual mechanical and LIPUS stimulation, enhancing the functional repair of AWD. This exercise-mimetic ES triggered by SPT establishes an innovative therapeutic strategy for abdominal wall repair, demonstrating broad potential in regenerative medicine. The exercise-mimetic electrical stimulation system comprises a sandwich-like piezoelectric patch constructed from aligned PCL-chitin-PCL nanofiber mats. It converts both endogenous and exogenous mechanical stimuli into electrical signals, thereby restoring local electric field homeostasis and promoting muscle differentiation and regeneration. The resulting bioelectrical cues act synergistically with the anisotropic topography to guide myofiber alignment and enhance myogenic differentiation via the Ca 2+ /CaN/NFAT2 pathway, ultimately facilitating functional muscle regeneration and reducing fibrosis in abdominal wall defect repair.