TY - JOUR
KW - Biomedical Engineering
KW - Biomimetics
KW - Lab-on-a-chip
KW - Respiratory system models
KW - Tissue engineering
AU - Jungwook Paek
AU - Lakshminarayan Reddy Teegala
AU - Farid Alisafaei
AU - Anika Alim
AU - Joseph W. Song
AU - Sunghee E. Park
AU - Jeehan Chang
AU - Haijiao Liu
AU - Bang-Jin Kim
AU - Sandra Ryeom
AU - Vivek Shenoy
AU - Geremy C. Clair
AU - Charles Thodeti
AU - Sailaja M. Paruchuri
AU - Dan Dongeun Huh
AB - Structural remodelling of living tissues due to mechanical forces is a common occurrence that plays an essential role in development, health and disease, but preclinical investigation of this dynamic process in human-relevant conditions remains a challenge. Here we present a microphysiological system integrated with pneumatically addressable soft actuators to emulate dynamic mechanical loading of mucosal tissues in the human respiratory tract. Using this system, we created a clinically relevant model of airway constriction in distal regions of asthmatic lungs to show compressive force-induced fibrotic airway remodelling. Following in vivo validation, we generated vascularized airway constructs in this model to investigate abnormal vascular remodelling in asthma, revealing airway constriction-induced subepithelial fibrosis as a key contributor to increased vascularity of asthmatic airways. Furthermore, we identified molecular mediators of abnormal airway remodelling through proteomics analysis of our microphysiological system and tested the feasibility of pharmacologically modulating their activity. We believe that our technology provides a useful tool for studying biophysical control and dysregulation of dynamic tissue remodelling in lungs and other mechanically active organs.
BT - Nature Biomedical Engineering
DA - 2026-05-11
DO - 10.1038/s41551-026-01669-9
LA - en
N2 - Structural remodelling of living tissues due to mechanical forces is a common occurrence that plays an essential role in development, health and disease, but preclinical investigation of this dynamic process in human-relevant conditions remains a challenge. Here we present a microphysiological system integrated with pneumatically addressable soft actuators to emulate dynamic mechanical loading of mucosal tissues in the human respiratory tract. Using this system, we created a clinically relevant model of airway constriction in distal regions of asthmatic lungs to show compressive force-induced fibrotic airway remodelling. Following in vivo validation, we generated vascularized airway constructs in this model to investigate abnormal vascular remodelling in asthma, revealing airway constriction-induced subepithelial fibrosis as a key contributor to increased vascularity of asthmatic airways. Furthermore, we identified molecular mediators of abnormal airway remodelling through proteomics analysis of our microphysiological system and tested the feasibility of pharmacologically modulating their activity. We believe that our technology provides a useful tool for studying biophysical control and dysregulation of dynamic tissue remodelling in lungs and other mechanically active organs.
PY - 2026
SP - 1
EP - 22
T2 - Nature Biomedical Engineering
TI - Mechanical force-induced tissue remodelling in a clinically relevant microphysiological model of asthmatic human lungs
UR - https://www.nature.com/articles/s41551-026-01669-9
Y2 - 2026-05-18
SN - 2157-846X
ER -