A Conformal Wearable Ultrasound Bioelectronics for Mechanotherapy Reprogramming of Fibroblast Plasticity via Wnt‐FGF10 Axis to Overcome Fibrotic Healing in Urethral Regeneration

ABSTRACT Postoperative fibrotic complications persistently challenge urethral reconstruction due to dysregulated stromal repair and poor graft integration. Conventional rigid ultrasound transducers lack anatomical conformity on dynamic tissues, limiting therapeutic efficacy. Here, we introduce a conformal, wearable low‐intensity pulsed ultrasound (LIPUS) bioelectronic system that overcomes these constraints via controlled adhesion printing and liquid metal interconnects. This low‐cost (<$20), flexible device ensures stable acoustic coupling and programmable mechanostimulation while maintaining mechanical integrity and biocompatibility under repeated use. In a rabbit model of full‐thickness urethral defect, LIPUS significantly improves luminal patency and urinary flow function, promotes angiogenesis and elastic fiber regeneration, while suppressing collagen deposition and pro‐inflammatory macrophage infiltration. Integrated multi‐omics and single‐nucleus RNA sequencing reveal that LIPUS activates the Wnt pathway to drive fibroblast differentiation into a terminally differentiated FGF10 ⁺ subset (FB3), which engages in regenerative crosstalk with mural cells via FGF10‐FGFR2b signaling and calcium dynamics. Wnt inhibition abrogates this process, confirming mechanistic specificity. This study bridges flexible bioelectronics with deep mechanobiology, providing new insights into how mechanical stimulation can redirect fibroblast fate and override pathological fibrosis, offering a scalable therapeutic framework for fibrotic disorders.