Extracellular matrix remodeling by dynamic strain in a three-dimensional tissue-engineered human airway wall model

Area of Science:

• Pulmonary Medicine
• Biomedical Engineering
• Cell Biology

Background:

• Airway wall remodeling, including subepithelial thickening and extracellular matrix (ECM) remodeling, is a key feature of asthma.
• The role of mechanical stress from hyperresponsive smooth muscle cells in this remodeling within a complex 3D environment remains unclear.

Purpose of the Study:

• To investigate the impact of dynamic compression on ECM remodeling in a physiologically relevant 3D human airway wall model.
• To characterize the cellular and molecular responses to mechanical strain in this engineered tissue.

Main Methods:

• A tissue-engineered human airway wall model was created using bronchial epithelial cells and lung fibroblasts within a collagen gel.
• Dynamic lateral compressive strain (10% or 30% at 1 or 60 cycles/hour) was applied using a novel device.
• ECM remodeling was quantified using immunohistochemistry and zymography.

Main Results:

• Dynamic compressive strain induced significant airway wall remodeling, characterized by increased deposition of type III and IV collagen.
• Increased secretion of matrix metalloproteinase-2 and -9 was observed, alongside enhanced myofibroblast differentiation.
• The spatial distribution of type III collagen and myofibroblasts suggested epithelial-fibroblast signaling influenced the remodeling response.

Conclusions:

• Dynamic mechanical compression in a 3D airway model recapitulates key features of asthma-associated airway remodeling.
• This remodeling is dependent on fibroblast activity and epithelial-fibroblast communication, occurring independently of inflammation.