Scholarlink

<p>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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 发表日期：

    2026年5月11日

查看全文
  • Jungwook Paek,
  • Lakshminarayan Reddy Teegala,
  • Farid Alisafaei,
  • Anika Alim,
  • Joseph W. Song,
  • Sunghee E. Park,
  • Jeehan Chang,
  • Haijiao Liu,
  • Bang-Jin Kim,
  • Sandra Ryeom,
  • Vivek Shenoy,
  • Geremy C. Clair,
  • Charles Thodeti,
  • Sailaja M. Paruchuri,
  • Dan Dongeun Huh

摘要

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.