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Advances in lung biomimetic systems: exploring biophysical cues in lung regenerative medicine
Shiyuan Bian1, Jason Say2, Dana Brinson3
1Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8; Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, University Health Network, Toronto General Hospital, University of Toronto, 101 College Street, Toronto, Ontario, Canada, M5G 0A3.
Abstract:
The COVID-19 pandemic highlighted the urgent need for advanced lung regenerative medicine. While traditional research focused on biochemical pathways, biophysical cues are equally critical regulators of lung cell behavior. This review discusses the role of key mechanical cues including cyclic stretch, strain/pressure, geometry, and matrix stiffness on lung cells in health and disease. The focus is on the evaluation of biomimetic platforms (decellularized scaffolds, dynamic surfaces, biomaterial constructs, and lung-on-chip devices) that recapitulate these environments; and the paradigm shifts in the field which show the importance of physiologically relevant systems. Finally, we identify challenges and future directions for translating mechanobiology-informed approaches into clinical therapies, highlighting their transformative potential for lung tissue engineering.
