A roadmap to stopping an incurable lung disease

Idiopathic pulmonary fibrosis is a devastating lung disease that is incurable, fatal, and challenging to diagnose. It causes the excessive deposition of extracellular matrix within lung tissue, alteration of the 3D lung microenvironment, and changes in tissue mechanical properties that impair gas exchange functions and eventually lead to death. Approved drugs developed for pulmonary fibrosis focus on treating symptoms at the cellular level, with an increasing focus on the role of the extracellular matrix in the development and progression of the disease.

This shift in understanding and treatment necessitates the development of complex in vitro models that more closely mimic human lungs. Dabaghi et al. presented a roadmap for improving these models for studying pulmonary fibrosis.

“Pre-clinical in vitro models are increasingly embracing complexity over simplicity, and integrating biochemical, biophysical, and mechanical cues that exist in the in situ healthy and diseased 3D lung microenvironments,” author Jeremy Hirota said.

The authors summarized known processes in pulmonary fibrosis, the role of the extracellular matrix in these pathologies, and discussed the parameters that should be considered, like cell types and inclusion of dynamic forces, when evaluating or developing an in vitro model. They hope to motivate the biomedical scientists, biomedical engineers, and materials researchers working to fabricate models that more closely mimic human lungs in health and disease.

They conclude by discussing future directions for even more advanced models, including tunable biomaterials that can interact with cells and change properties in real time.

Source: “A roadmap for developing and engineering in vitro pulmonary fibrosis models,” by Mohammadhossein Dabaghi, Mabel Barreiro Carpio, Neda Saraei, Jose Manuel Moran-Mirabal, Martin R. Kolb, and Jeremy A. Hirota, Biophysics Reviews (2023). The article can be accessed at https://doi.org/10.1063/5.0134177 .