143 3D lung models – 3D extracellular matrix models Figure 3: Generation and usage of decellularized lung ECM as a hydrogel. A) Different methods applied to decellularize lung tissue include physical methods such as freeze thawing or sonication, chemical methods that employ (combination of) detergents and acidic/alkaline solutions and enzymatic methods with endonucleases or exonucleases. Combinations of physical, chemical and enzymatic decellularization methods has also been employed. B) Schematic representation of generation of ECM-derived hydrogels from the decellularized lung ECM. Lung ECM powder, which is obtained after freeze-drying and grinding the decellularized lung scaffold, is digested using pepsin in acidic media. Then, the resulting solution is brought back to pH 7.4 and supplemented with PBS to equilibrate the salt concentration. This solution, also called “pre-gel” can form hydrogels irreversibly once it is incubated at 37°C. Apart from IPF, acellular scaffolds have also been derived from COPD lung tissue. COPD derived bronchial epithelial cells had enhanced proliferative capacity and maintained basal cell phenotype when seeded on COPD-derived decellularized bronchial constructs compared to non-diseased scaffolds [146]. In contrast, no variation was observed in the differentiation or proliferative potential of emphysematous lung-derived mesenchymal stromal cells grown on decellularized 6
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