Modeling functional responses to pollutant exposure using modular hydrogel supported vascularized...

Area of Science:

• Biomaterials Science
• Cell Biology
• Regenerative Medicine

Background:

• Alveolar type 2 (AT2) cells are vital for lung homeostasis.
• Three-dimensional alveolospheres are valuable models for lung research.
• Understanding extracellular matrix (ECM) influence on AT2 cells is critical.

Purpose of the Study:

• To identify key ECM characteristics for AT2 alveolosphere formation and growth.
• To develop advanced lung models for disease and drug discovery.

Main Methods:

• Encapsulating AT2 cells in various ECM-based hydrogels.
• Assessing alveolosphere formation with different matrix compositions and stiffness.
• Developing a multicellular vascularized alveolosphere-on-a-chip model.

Main Results:

• Laminin identified as a key ECM protein supporting alveolosphere formation.
• Low matrix stiffness and high compliance promoted greater alveolosphere formation.
• Inhibition of matrix degradation and cellular contractility disrupted formation.
• A vascularized alveolosphere-on-a-chip model was successfully developed.

Conclusions:

• Physicochemical properties of the ECM critically influence alveolosphere formation.
• The developed platform advances lung biology, disease mechanism, and drug discovery studies.
• The model is useful for evaluating chemical exposures on alveolar cells.