Mechanical force-induced tissue remodelling in a clinically relevant microphysiological model of asthmatic human lungs.

Summary

This organ-level microphysiological platform demonstrates that dynamic mechanical constriction alone can drive subepithelial fibrosis and increased vascularity in asthma-like airways, and it identifies molecular mediators amenable to pharmacologic modulation. The work bridges mechanobiology with translational targeting in a clinically relevant human model validated in vivo.

Key Findings

• Dynamic airway constriction in a human microphysiological system induces subepithelial fibrosis in distal asthmatic-like airways.
• Vascularized airway constructs revealed airway constriction-driven increases in vascularity via subepithelial fibrosis.
• Proteomics identified mediators of remodeling, and pharmacologic modulation was feasible in the platform.
• Findings were validated with in vivo data, enhancing translational relevance.

Clinical Implications

Reframes asthma as, in part, a mechanobiological disease: therapies targeting mechano-transduction and identified mediators may prevent or reverse subepithelial fibrosis and aberrant vascular remodeling. Offers a human-relevant testbed for precision therapeutics.

Limitations

• In vitro microphysiological system may not capture full systemic immune and multicellular interactions of in vivo asthma.
• Short- to mid-term remodeling dynamics; long-term reversibility and clinical efficacy remain untested.

Future Directions

Map causal mechano-transduction pathways to specific mediators, test anti-fibrotic/anti-angiogenic strategies, and validate biomarkers/endpoints for early-phase clinical trials targeting mechanically driven asthma endotypes.