Mechanomedicine for lung transplantation

As the definitive therapeutic intervention for end-stage lung diseases, lung transplantation continues to face limitations due to postoperative complications and graft rejection. Conventional research has predominantly focused on biochemical pathways, neglecting the biomechanical nature of the lungs as dynamic respiratory organs. Herein, we propose time the conceptual framework of "mechanomedicine in lung tTransplantation" (MLT), establishing an integrated "assessment-intervention" lifecycle management model through the convergence of biomechanics, mechanobiology, and clinical medicine. Preoperatively, multiscale biomechanical evaluation, including organ-level lung compliance matching, molecular-level extracellular matrix (ECM) stiffness analysis, and mechanosensitive pathway profiling, optimizes donor-recipient compatibility and enhances functional reserves in marginal donor lungs. Intraoperatively, fiber-optic Bragg grating sensor networks and 4D-printed biocompatible scaffolds enable real-time vascular-airway biomechanical adaptation, complemented by lung-protective ventilation strategies to minimize iatrogenic injury. Postoperatively, targeted modulation of ECM stiffness, pharmacological inhibition of the YAP/TAZ mechanotransduction axis, and restoration of mitochondrial calcium homeostasis collectively recalibrate the biomechanical microenvironment to attenuate pathological remodeling. Mechanistically, we elucidate how mechanical cues orchestrate immune dysregulation and tissue fibrosis through cross-scale networks (molecular-cellular-organ), thereby proposing a novel "mechano-biochemical dual-axis coupling" paradigm. This work provides a translational roadmap from theoretical foundations to clinical implementation, heralding a paradigm shift in transplant medicine toward proactive biomechanical modulation.