ArticleRespiratory research2026
Extracellular matrix remodeling modifies structural responses to ventilator-induced lung injury: a multiscale correlative imaging study.
Article in Respiratory research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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15 authors.
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Abstract
backgroundMechanical ventilation (MV) can induce or exacerbate ventilator-induced lung injury (VILI), particularly in mechanically heterogeneous lungs with pre-existing injury.
methodsWe investigated VILI in a rat model of bleomycin-induced lung injury and compared it with healthy controls using a combined in-vivo and ex-vivo imaging approach. Previously acquired in-vivo data from four-dimensional (4D) phase-contrast synchrotron micro-computed tomography (micro-CT) and forced oscillation measurements showed increased lung elastance and reduced local acinar deformation in bleomycin-induced injured lungs at baseline and after injurious MV. To identify structural and mechanical correlates, we performed automated three-dimensional (3D) pore analysis and atomic force microscopy (AFM) on formalin-fixed, paraffin-embedded lung tissue, complemented by histology and spatial co-registration.
resultsEx-vivo analysis revealed pronounced airspace enlargement after both injurious MV of healthy lungs, and in bleomycin-injured lungs with inflammation and early fibrotic changes, with the strongest cumulative effect in combined bleomycin and VILI. AFM demonstrated region-specific mechanical responses, and correlation analyses linked pore geometry and nanoscale stiffness to in-vivo lung mechanics. Spatial analysis further showed co-localization of VILI-associated airspace damage with injured regions.
conclusionsExtracellular matrix remodelling modifies the lung's response to injurious mechanical ventilation, with VILI-associated airspace damage preferentially co-localising with regions of pre-existing matrix injury. This multiscale correlative approach provides mechanistic insight into the interplay between lung injury and VILI and informs ventilation strategies in structurally altered lungs.
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