Chronic lung diseases such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are associated with changes in the extracellular matrix (ECM) composition and abundance affecting the mechanical properties of the lung. This study aimed to generate ECM hydrogels from control, severe COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) IV) and IPF human lung tissue and evaluate if their stiffness and viscoelastic properties were reflective of native

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... tissue. For hydrogel generation, control, COPD GOLD IV and fibrotic human lung tissue was decellularized, lyophilized, ground into powder, porcine pepsin solubilized, buffered with PBS, and gelled at 37°C. Viscoelastic properties from tissues and hydrogels were assessed using a low load compression tester (LLCT) measuring the stiffness and viscoelastic properties in terms of a generalized Maxwell model representing phases of viscoelastic relaxation. The ECM hydrogels had a higher stress relaxation than tissue. ECM hydrogels required 3 Maxwell elements with slightly slower relaxation times (τ) than that of native tissue which required 4 elements. The relative importance (RI) of the first Maxwell element contributed the most in ECM hydrogels whereas for tissue the contribution was spread out over all 4 elements. IPF tissue had a longer lasting 4th element with a higher RI than the other tissues and IPF ECM hydrogels did require a 4th Maxwell element in contrary to all other ECM hydrogels. This study shows that hydrogels composed of native human lung ECM can be generated. Stiffness of ECM hydrogels resembled that of whole tissue while viscoelasticity differed