172 Chapter 7 emerging knowledge about ECM mechanical properties and the functional impacts of these microenvironment parameters. Another important property which goes hand-in-hand with mechanics is topography, reflecting the fibrous landscape within the ECM-derived hydrogels. In chronic lung diseases like COPD or lung fibrosis, the ECM topography is altered next to the mechanical properties of ECM [28, 60-63]. Using lung ECM sourced from diseased human lungs, for the generation of the hydrogels, would inherently convey (most of) the biochemical composition and resemble the mechanical properties; however, the native architecture of the lung ECM assembly is lost during the process of preparing ECM-derived hydrogels. Recently, preparing porcine lung ECM hydrogels with micropatterned surfaces was described as a method to prepare arrays for drug screening [64]. This study demonstrates the preparation of spherical patterns on the hydrogel surface with different diameters, although the aspects of altering the hydrogel surface to guide cell fate, behaviour or differentiation remain unexplored. Alternatively, electrospinning could provide another opportunity to alter the structural organization of the fibres [65]. While electrospun Poly(L-lactic acid)(PLLA)/ porcine lung ECM hybrid scaffolds have been previously established [66], there is no report of electrospinning of pure decellularized lung ECM. Developing novel tools to modify the topography of the ECM fibres within the hydrogels and the regulation of the structural arrangements within these hydrogels requires more attention. Surface modifications on non-ECM-derived hydrogels is not a novel concept [67, 68], yet little is known about applying such modifications to the locations within the hydrogels in different planes in order to mimic the architecture of the native lung tissue. The details of measuring, reporting and altering the properties of lung ECM-derived hydrogels gain more importance as the field progresses. Unfortunately to date, attempts at modifying properties of lung ECM-derived hydrogels remain rather limited. While the latest studies have focused on altering mechanical properties at a global level, new and innovative methodologies that will allow us to initiate more targeted modifications in such properties are required. Especially considering the heterogeneity of lung tissue and its architecture, having more control over spatial distribution of alterations in mechanical properties would enhance the in vivo mimicking capacity of our models.
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