title: Bioprinting the Cancer Microenvironment.
abstract: Cancer is intrinsically complex, comprising both heterogeneous cellular compositions and microenvironmental cues. During the various stages of cancer initiation, development, and metastasis, cell-cell interactions (involving vascular and immune cells besides cancerous cells) as well as cell-extracellular matrix (ECM) interactions (e.g., alteration in stiffness and composition of the surrounding matrix) play major roles. Conventional cancer models both two- and three-dimensional (2D and 3D) present numerous limitations as they lack good vascularization and cannot mimic the complexity of tumors, thereby restricting their use as biomimetic models for applications such as drug screening and fundamental cancer biology studies. Bioprinting as an emerging biofabrication platform enables the creation of high-resolution 3D structures and has been extensively used in the past decade to model multiple organs and diseases. More recently, this versatile technique has further found its application in studying cancer genesis, growth, metastasis, and drug responses through creation of accurate models that recreate the complexity of the cancer microenvironment. In this review we will focus first on cancer biology and limitations with current cancer models. We then detail the current bioprinting strategies including the selection of bioinks for capturing the properties of the tumor matrices, after which we discuss bioprinting of vascular structures that are critical toward construction of complex 3D cancer organoids. We finally conclude with current literature on bioprinted cancer models and propose future perspectives.
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 65 Landsdowne Street, Cambridge, Massachusetts 02139, United States; Harvard-MIT Division of Health Sciences and Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States; Wyss Institute for Biologically Inspired Engineering, Harvard University, 3 Blackfan Circle, Boston, Massachusetts 02115, United States.
authors.forename: Yu Shrike
authors.initials: YS
authors.lastname: Zhang
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 65 Landsdowne Street, Cambridge, Massachusetts 02139, United States; Harvard-MIT Division of Health Sciences and Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States; Department of Bioengineering, École Polytechnique Fédérale de Lausanne, Route Cantonale, Lausanne 1015, Switzerland.
authors.forename: Margaux
authors.initials: M
authors.lastname: Duchamp
authors.affiliation: Division of Vascular & Interventional Radiology, Mayo Clinic, 13400 East Shea Boulevard, Scottsdale, Arizona 85259, United States.
authors.forename: Rahmi
authors.initials: R
authors.lastname: Oklu
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, 55 Fruit Street, Boston, Massachusetts 02114, United States.
authors.forename: Leif W
authors.initials: LW
authors.lastname: Ellisen
authors.affiliation: Harvard-MIT Division of Health Sciences and Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States; Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, United States; Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 65 Landsdowne Street, Cambridge, Massachusetts 02139, United States; Harvard-MIT Division of Health Sciences and Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States; Wyss Institute for Biologically Inspired Engineering, Harvard University, 3 Blackfan Circle, Boston, Massachusetts 02115, United States; Department of Bioindustrial Technologies, College of Animal Bioscience and Technology, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea; Department of Physics, King Abdulaziz University, Abdullah Sulayman Street, Jeddah 21569, Saudi Arabia.
authors.forename: Ali
authors.initials: A
authors.lastname: Khademhosseini
keywords: bioprinting; cancer biology; cancer model; drug screening; vascularization