3d-printing-vitro-hydrogel-microcarriers-alternating-viscous-inertial

3D Printing of <em>In Vitro</em> Hydrogel Microcarriers by Alternating Viscous-Inertial Force Jetting

Microcarriers are beads with a diameter of 60-250 &#181;m and a large specific surface area, which are commonly used as carriers for large-scale cell ...

Tsinghua University

Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing

Resolving the origin and development of tumor heterogeneity has proven to be a crucial challenge in cancer research. In vitro tumor models have been widely used for both scientific and clinical research. Currently, tumor models based on 2D cell culture, animal models, and 3D cell-laden constructs are widely used. Heterogeneous tumor models, which consist of more than one cell type and mimic cell-cell as well as cell-matrix interactions, are attracting increasing attention. Heterogeneous tumor models can serve as pathological models to study the microenvironment and tumor development such as tumorigenesis, invasiveness, and malignancy. They also provide disease models for drug screening and personalized therapy. In this review, the current techniques, models, and oncological applications regarding 3D heterogeneous tumor models are summarized and discussed.

Review on biofabrication and applications of heterogeneous tumor models.

Studying biological characteristics of tumors and evaluating the treatment effects require appropriate in vitro tumor models. However, the occurrence, progression, and migration of tumors involve spatiotemporal changes, cell-microenvironment and cell-cell interactions, and signal transmission in cells, which makes the construction of in vitro tumor models extremely challenging. In the past few years, advances in biomaterials and tissue engineering methods, especially development of the bioprinting technology, have paved the way for innovative platform technologies for in vitro cancer research. Bioprinting can accurately control the distribution of cells, active molecules, and biomaterials. Furthermore, this technology recapitulates the key characteristics of the tumor microenvironment and constructs in vitro tumor models with bionic structures and physiological systems. These models can be used as robust platforms to study tumor initiation, interaction with the microenvironment, angiogenesis, motility and invasion, as well as intra- and extravasation. Bioprinted tumor models can also be used for high-throughput drug screening and validation and provide the possibility for personalized cancer treatment research. This review describes the basic characteristics of the tumor and its microenvironment and focuses on the importance and relevance of bioprinting technology in the construction of tumor models. Research progress in the bioprinting of monocellular, multicellular, and personalized tumor models is discussed, and comprehensive application of bioprinting in preclinical drug screening and innovative therapy is reviewed. Finally, we offer our perspective on the shortcomings of the existing models and explore new technologies to outline the direction of future development and application prospects of next-generation tumor models.

Bioprinting of in vitro tumor models for personalized cancer treatment: a review.

Towards the development of in vivo-mimicking tumor model for extensive study of tumorigenesis and establishment of personalized therapy, patient-derived primary tumor cells were employed in this work for three-dimensional (3D) bioprinting. Intrahepatic cholangiocarcinoma cells isolated from patient were bioprinted using a composite hydrogel system of gelatin-alginate-Matrigel into pre-designed grid architecture. ICC cells were observed to process a colony forming ability with high survival rate and active proliferation. Expression levels of tumor markers, cancer stem cell markers, matrix metalloproteinase protein, index of tumor fibrosis, index of liver function, and epithelial-mesenchymal transition regulatory proteins confirmed the development of the invasive and metastatic phenotype of the intrahepatic cholangiocarcinoma cells in the 3D printed tumor microenvironment. Similar results were obtained in anti-cancer drug resistance of the intrahepatic cholangiocarcinoma cells in the 3D bioprinted construct that demonstrated stem-like properties, which suggested the promising potential of current 3D printed tumor model in the development of personalized therapy, especially for discovery of more conducive targeted drugs.

Article	Year
Review on biofabrication and applications of heterogeneous tumor models. Journal of tissue engineering and regenerative medicine\| PubMed ID: 31359625	2019
Bioprinting of in vitro tumor models for personalized cancer treatment: a review. Biofabrication\| PubMed ID: 32470967	2020
Bioprinting of patient-derived in vitro intrahepatic cholangiocarcinoma tumor model: establishment, evaluation and anti-cancer drug testing. Biofabrication\| PubMed ID: 32599574	2020

Tiankun Liu

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