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International Journal of Bioprinting                                      In vitro 3D pancreatic acinar unit






















































            Figure 3. Viability and distribution of stromal cells in 3D MEW scaffolds. (a) Metabolic activity of fibroblasts seeded on MEW scaffolds as a function
            of time, measured from the reduction of resazurin (n = 3). Tukey’s multiple comparisons test: *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. (b)
            Representative confocal images at 10× (i, iii, v) and 20× (ii, iv, vi) magnifications of HFF1 at 14, 21, and 28 days after seeding. Scale bars: 100 µm (i) and
            50 µm (ii). (c) Scanning electron microscopy (SEM) images at different magnifications showing the HFF1 colonization within the MEW constructs. Scale
            bars: 500 µm (i, iv, vii), 100 µm (ii, v, viii), and 20 µm (iii, vi, ix).

            pancreatic unit (epithelial cells surrounded by stromal   environment respond to drugs differently than cells
            cells). After 7, 10, and 14 days in co-culture, HPDE-KRAS   in two-dimensional models and show features more
            cells visibly proliferated within the MEW model, growing   similar to the ones typical of PDAC components (e.g.,
            on fibers and on the stromal tissue and colonizing most of   chemoresistance, biochemical gradients, tumor–stroma
            the cavity’s bottom.                               cytoarchitecture). 47-51  For this reason, pancreatic cancer
                                                               research has been oriented in recent years toward the
            4. Discussion                                      development of novel in vitro models such as organ-on-

            Two-dimensional models are valuable low-cost systems   chip and 3D models that better mimic the human tumor
            that can be easily applied in in vitro experiments,  but they   for in vivo conditions, for addressing ethical concerns in
                                                  45
            are unable to recapitulate the biological and biophysical   animal experiments, and to deepen our understanding
            complexity of human tumor microenvironment.        of PDAC physiopathology. 52,53  So far, only few studies
                                                         46
            Indeed, several studies have largely proved that pancreatic   focused  on replicating the  3D  gland geometry of  the
            cancer  and stromal  cells  grown in  a  3D bioengineered   functional unit of exocrine pancreas, 23-25,54,55  but they


            Volume 10 Issue 2 (2024)                       420                                doi: 10.36922/ijb.1975
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