24 Chapter 2 Figure 2: Representative scanning electron microscopy (SEM) images of decellularized lung parenchyma from non-disease control donors (upper row) and IPF patients (lower row). One of the mechanisms by which abnormal topography plays a role in lung fibrosis is the altered microstructures in the protein organization. In a study by Seo et al., comparison of adipose-derived stromal cells seeded on collagen type I networks with thin fibers and low pore size to cells seeded on networks with thick fibers and bigger pore size revealed that changing the microstructure increased differentiation of these stromal cells to myofibroblasts ~1.5X [39]. Along with fiber thickness and pore size, fiber alignment is an important parameter in ECM topography. Increased migration speed of primary lung fibroblasts seeded on collagen type I -methacrylated gelatin hydrogels was observed in highly aligned network samples, compared to hydrogels with less aligned networks [40]. In another study, increasing fiber density independent of the stiffness resulted in higher surface area of seeded dermal fibroblasts in 3D in vitro culture [41]. While collagen type I hydrogels with different stiffness values were used to test the effect of microstructure in the study by Seo et al., it is difficult to conclude the stiffness-independent contribution of the microstructure. As the abovementioned changes (stiffness, viscoelasticity and topography) in the fibrotic ECM occur simultaneously during fibrosis, more studies using advanced biomaterials are required to examine the individual contributions of such properties to the perpetuation of the fibrotic response.
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