Extracellular matrix hydrogels derived from human lung replicate biomechanics of native tissue
Cellular and molecular mechanisms (English)Rationale: The extracellular matrix (ECM) composition changes in disease, which influences the mechanical properties of the lung. This study aimed to characterize the stiffness and viscoelasticity of nondiseased, COPD and fibrotic lung tissue in comparison to lung-derived ECM hydrogels.
Methods: Human explanted lung (nondiseased n=4, COPD n=4 and pulmonary fibrosis n=1) was assessed using a low load compression tester (LLCT) measuring stiffness, viscoelastic stress relaxation and Maxwell elements representing phases of viscoelastic relaxation. For hydrogel creation, tissue was decellularized, lyophilized, ground into a powder, porcine pepsin solubilized, buffered with PBS, pH neutralized, gelled at 37°C and measured with the LLCT. Measurements where obtained from 3 locations per tissue piece and for each hydrogel 4 replicates were measured on 3 occasions.
Results: Hydrogels were generated from nondiseased, COPD and fibrotic human lung tissue. The stiffness and viscoelastic data of the tissues, and corresponding hydrogels, are presented in table 1.
Conclusions: This study shows for the first time the possibility to generate ECM hydrogels from nondiseased and diseased human lung. The stiffness and viscoelasticity characteristics of whole tissue remained present in the ECM hydrogels; the stiffness resembles that of native tissue reported in Booth et al. Am J Respir Crit Care Med 2012.
Table 1. Stiffness and viscoelastic properties of nondiseased, COPD and IPF human lung tissue compared to that of corresponding ECM hydrogels