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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

