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International

                                                                         Journal of Bioprinting



                                        RESEARCH ARTICLE
                                        Melt-electrowriting of 3D anatomically relevant

                                        scaffolds to recreate a pancreatic acinar unit
                                        in vitro



                                        Viola Sgarminato 1,2,3 , Michela Licciardello 1,2,3 , Gianluca Ciardelli 1,2,3,4† ,
                                        and Chiara Tonda-Turo 1,2,3 †
                                                              *
                                        1 Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Turin, Italy
                                        2 POLITO BIOMedLAB, Politecnico di Torino, Turin, Italy
                                        3 Interuniversity Center for the Promotion of the 3Rs Principles in Teaching and Research, Pisa, Italy
                                        4 CNR-IPCF, National Research Council-Institute for Chemical and Physical Processes, Pisa, Italy
                                        (This article belongs to the Special Issue: 3D Bioprinting for Tumor Modeling)


                                        Abstract
                                        Melt-electrowriting (MEW) belongs to the group of advanced additive manufacturing
                                        techniques and consists of computer-aided design (CAD)-assisted polymer extrusion
                                        combined with a high-voltage supply to achieve deposition of polymeric fibers
                                        with diameters in the micrometric range (1 to 20 µm) similar to the size of natural
                                        extracellular matrix fibers. In this work, we exploit MEW to design and fabricate a
                                        three-dimensional (3D) model that resembles the morphology of the exocrine
            † These authors contributed equally   pancreatic functional unit without the need of supports, mandrels, or sacrificial
            to this work.               materials. Optimized process parameters resulted in a MEW scaffold having regular
            *Corresponding author:      fibers (19 ± 5 µm size) and an acinar cavity showing high shape fidelity. Then, human
            Chiara Tonda-Turo           foreskin fibroblasts (HFF1) and human pancreatic ductal epithelial cells (HPDE), wild-
            (chiara.tondaturo@polito.it)
                                        type HPDE, and HPDE overexpressing KRAS oncogene were allowed to colonize the
            Citation: Sgarminato V, Licciardello   entire 3D structure and the acinar cavity. Thus, a physiologically relevant 3D model
            M, Ciardelli G, Tonda-Turo C.    was created in vitro after 24 days using a co-culture protocol (14 days of HFF1 alone
            Melt-electrowriting of 3D
            anatomically relevant scaffolds to   plus 10 days of HPDE and HFF1 co-culture). The effect of cell crosstalk within the
            recreate a pancreatic acinar unit    MEW scaffolds was also assessed by monitoring HFF1 secretion of interleukin (IL)-6,
            in vitro. Int J Bioprint.   a pro-inflammatory cytokine responsible for the inflammatory cascade occurring in
            2024;10(2):1975.
            doi: 10.36922/ijb.1975      pancreatic cancer. High levels of IL-6 were detected only when fibroblasts were co-
                                        cultured with the HPDE overexpressing KRAS. These findings confirmed that the MEW
            Received: October 6, 2023
            Accepted: November 17, 2023  3D in vitro model is able to recreate the characteristic hallmark of the pathological
            Published Online: February 23, 2024  condition where cancer oncogenes mediate fibroblast activities.
            Copyright: © 2024 Author(s).
            This is an Open Access article   Keywords: Melt-electrowriting; Exocrine pancreas; In vitro models; 3D scaffolds;
            distributed under the terms of the
            Creative Commons Attribution   Pancreatic ductal adenocarcinoma
            License, permitting distribution,
            and reproduction in any medium,
            provided the original work is
            properly cited.
                                        1. Introduction
            Publisher’s Note: AccScience
            Publishing remains neutral with   Pancreatic adenomeres secreting the digestive enzymes are the functional units of exocrine
            regard to jurisdictional claims in
            published maps and institutional   pancreas and are the sites where the first lesions of pancreatic ductal adenocarcinoma
            affiliations.               (PDAC) develop. In pancreas, an adenomere is constituted by acinar and ductal




            Volume 10 Issue 2 (2024)                       413                                doi: 10.36922/ijb.1975
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