Page 484 - IJB-10-3

International Journal of Bioprinting Stretchable scaffold for modeling fibrosis

2.13. Statistical analysis The scaffold mesh geometry was first defined (Figure 1),
Statistical analysis of variance (ANOVA) was performed and PCL scaffolds with biomimetic stiffness were designed
using GraphPad Prism version 9.0.0 (GraphPad Software accordingly. Scaffolds with different numbers of layers
Inc., USA). (two, three, four, seven, and eight layers) were subjected
to structural analysis under S-L.B. and C.B. hypotheses.
3. Results and discussion Structure displacement computation was performed for
stiffness analytic evaluation, considering both tensile force
In this work, bioartificial PCL/GelMA scaffolds were and bending moment (Figure S1). The analysis utilized
designed and fabricated. These scaffolds were able to Young’s modulus (E) and yield stress (σ ) values of single
reproduce the stiffness of human cardiac fibrotic tissue to PCL filaments fabricated by MEX that were measured by
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sustain in vivo-like cyclic mechanical deformations and uniaxial tensile mechanical tests (E = 444 ± 46.32 MPa
support HCF culture. The ability of bioartificial scaffolds to and σ = 17.15 ± 2.36 MPa). Figures 5 and 9A displayed
sustain cyclic mechanical deformations was imparted by the the stiffness of PCL scaffolds as a function of the number
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PCL scaffold architecture, while stiffness could be adjusted by of scaffold layers, calculated according to the S-L.B. and
both the number of PCL scaffold layers and the concentration C.B. approximations. Considering the PCL single filament
of GelMA hydrogels. Notably, the GelMA hydrogel section area (b × h) of 0.2 × 0.15 mm , measured from SEM
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concentration in bioartificial scaffolds was also optimized images (not shown), scaffold stiffness was found to increase
by static in vitro tests with HCFs to allow their long-term as a function of the number of scaffold layers containing
culture for at least 14 days. Finally, PCL/GelMA scaffolds wavy filaments. Specifically, stiffness values increased
cellularized with HCFs were cultured in dynamic conditions twofold with the addition of any new layer containing
under cyclic mechanical stimulation to preliminarily assess wavy filaments, while layers containing straight filaments
the activation of HCFs into myofibroblasts. did not affect scaffold stiffness. This was a consequence of

3.1. Design and characterization of stretchable the dependence of the area moment on the scaffold cross-
poly(ε-caprolactone) scaffolds section. Indeed, the scaffold cross-section perpendicular to
PCL scaffolds with cardiac tissue-like stretchability were the x-direction (Figure 1) increased with the addition of any
designed to have a tailored mesh geometry with fixed new layer containing wavy filaments. Hence, scaffolds with
filament size and a varying number of superimposed three, four, seven, and eight layers, that is, having the same
layers, to: (i) mimic the stiffness of human cardiac fibrotic number of layers with wavy filaments, displayed the same
tissues (Young’s modulus of 0.4–9 MPa, as measured by stiffness. As similar results were obtained using both S-L.B.
uniaxial tensile tests using a 500 N load cell); (ii) sustain and C.B. hypotheses (Figure 5), the S-L.B. approximation
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in vivo-like maximum elastic deformation (≤22%); (iii) was then selected for further stiffness evaluations.
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display fatigue resistance under uniaxial cyclic tensile tests The mechanical behavior (e.g., stress distribution) of
(with 22% maximum strain). PCL scaffolds with up to eight stacked layers (Figure 1)

Figure 5. PCL: Poly(ε-caprolactone) (PCL) scaffold stiffness computed by structural analysis based on approximations of the single mesh element as a
straight-line (S-L.B.) or a curved beam (C.B.). Abbreviations: C.B.: Curved beam; S-L.B.: Straight-line beam.

Volume 10 Issue 3 (2024) 476 doi: 10.36922/ijb.2247