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A microfluidic lung-on-a-chip based on biomimetic hydrogel membrane
Chong Shen1, Huiming Yang1, Wenqi She1
1Key Laboratory of Biomass Chemical Engineering (Education Ministry), College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang, China.
Biotechnology and Bioengineering
|May 17, 2023
Summary
Researchers developed a new lung-on-a-chip using a hydrogel membrane that better mimics the human lung's extracellular matrix. This improved model accurately reflects pulmonary fibrosis, offering a better tool for disease investigation and drug development.
Area of Science:
- Biomaterials Engineering
- Tissue Engineering
- Respiratory Medicine
Background:
- Lung-on-a-chip models are crucial for studying lung diseases.
- Existing models using polydimethylsiloxane (PDMS) membranes lack the compositional and mechanical properties of the natural alveolar basal membrane.
- This limitation hinders accurate recapitulation of lung physiology and disease pathology.
Purpose of the Study:
- To develop a novel lung-on-a-chip model with a biomimetic membrane.
- To improve the recapitulation of the alveolar mechanical microenvironment.
- To create a more accurate platform for studying pulmonary fibrosis and evaluating antifibrotic drugs.
Main Methods:
- Fabrication of a lung-on-a-chip device utilizing a thin, biocompatible F127-DA hydrogel membrane.
- Characterization of the hydrogel membrane's composition and mechanical properties to match the native alveolar extracellular matrix.
- Culturing human pulmonary artery endothelial cells (HPAEpiCs) and assessing epithelial/endothelial functions and barrier integrity.
- Inducing fibrotic conditions under varying mechanical strain to compare hydrogel-based and PDMS-based chips.
Main Results:
- The F127-DA hydrogel membrane closely mimicked the composition and stiffness of the human alveolar extracellular matrix.
- The hydrogel-based lung-on-a-chip successfully reconstructed alveolar mechanical microenvironments, enhancing epithelial/endothelial functions and barrier formation.
- Pulmonary fibrosis was observed on the hydrogel chip only under nonphysiologically high strain, unlike the accelerated fibrosis seen on PDMS chips, aligning better with in vivo observations.
- The hydrogel-based model demonstrated a more physiologically relevant response to fibrotic stimuli.
Conclusions:
- The F127-DA hydrogel-based lung-on-a-chip provides a superior biomimetic platform for studying lung diseases.
- This physiologically relevant model accurately reflects pulmonary fibrosis mechanisms.
- It serves as an ideal tool for investigating lung diseases and developing effective antifibrotic therapies.
