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International

                                                                         Journal of Bioprinting



                                        RESEARCH ARTICLE
                                        Bioprinting native-like 3D micro breast cancer

                                        tissues utilizing existing cancer cell lines



                                        Brian E. Grottkau 1,2† *, Zhixin Hui , and Yonggang Pang *
                                                                                       1
                                                                   1†
                                        1 The Laboratory for Therapeutic 3D Bioprinting, Department of Orthopedic Surgery, Massachusetts
                                        General Hospital, Harvard Medical School, Boston, Massachusetts, USA
                                        2 Department of Orthopedics, University of Miami Medical Center and Jackson Memorial Hospital,
                                        Miami, FL 33136, USA




                                        Abstract

                                        3D cancer cell models provide a more accurate representation of in vivo conditions
                                        than traditional 2D cultures. Many cancer cell lines, while stable and extensively
                                        characterized in 2D environments, often underperform compared to primary cells
                                        in 3D models due to the inherent resource constraints and variability of the latter.
                                        To bridge this gap and harness the full potential of established cancer cell lines, we
                                        adopted the innovative direct volumetric drop-on-demand (DVDOD) bioprinting
                                        methodology that we have developed previously, leading to the inception of
                                        printed micro-cancer tissues (PMCaTs). Our method, notable for its bioink droplet
                                        scattering technique, enables the generation of intricate features within a droplet,
                                        allowing for the creation of typical architectures of breast cancer tissue. We created
                                        PMCaTs that captured the essence of micro breast cancer tissues, from native-like
            † These authors contributed equally   ductal structures and cancer nests to the intricate cancer microenvironment. This
            to this work.
                                        encompasses elements like cancer-associated fibroblasts, detailed microvasculature,
            *Corresponding authors:     and regions marked by both intensive proliferation and hypoxia. These bioprinted
            Brian E. Grottkau
            (bxg1729@med.miami.edu)     models demonstrate long-term viability and are instrumental for diverse research
            Yonggang Pang               areas—from exploring cancer growth dynamics and hypoxia-induced behaviors
            (ypang11@outlook.com)       to investigating the nuances of microvasculature, drug penetration capabilities,
                                        immune responses, metastatic trends, and clinical drug response predictions.
            Citation: Grottkau BE, Hui Z,
            Pang Y. Bioprinting native-like    Ultimately, our groundbreaking DVDOD bioprinting technique holds the promise of
            3D micro breast cancer tissues   reshaping the landscape of cancer research, introducing advanced in vitro models
            utilizing existing cancer cell lines.    poised to transform therapeutic exploration.
            Int J Bioprint. 2024;10(3):2911.
            doi: 10.36922/ijb.2911
            Received: February 9, 2024  Keywords: Bioprinting; Direct volumetric drop-on-demand; 3D micro breast cancer
            Accepted: April 3, 2024     tissues; Native-like; Cancer cell lines; 3D models
            Published Online: June 13, 2024
            Copyright: © 2024 Author(s).
            This is an Open Access article
            distributed under the terms of the
            Creative Commons Attribution   1. Introduction
            License, permitting distribution,
                                                                                   1
            and reproduction in any medium,   Despite significant advancements in cancer research,  recapitulating the complexities
                                                                                                             2
            provided the original work is   of human tumors for in vitro drug testing and disease modeling remains a challenge.
            properly cited.             Numerous cancer cell lines have been established to deepen our comprehension of tumor
            Publisher’s Note: AccScience   biology and therapeutic responses. For example, the Cancer Cell Line Encyclopedia
            Publishing remains neutral with   (CCLE) offers over 1000 cell lines, providing a comprehensive molecular characterization
            regard to jurisdictional claims in                3
            published maps and institutional   resource for cancer research.  Similarly, the cancer therapeutics response portal (CTRP)
            affiliations.               provides over 900 cell lines, helping researchers tailor therapeutic strategies based on

            Volume 10 Issue 3 (2024)                       557                                doi: 10.36922/ijb.2911
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