Novel Bioprinted Pancreatic Tumor Model: A Translational Tool for Radiotherapy, Chemotherapy and Immunotherapy Efficacy Studies

Abstract

<h3>Purpose/Objective(s)</h3> Creation of first-ever bioprinted model of pancreatic ductal adenocarcinoma (PDAC) using extrusion bioprinting for radiotherapy, chemotherapy and immunotherapy screening and efficacy testing. <h3>Materials/Methods</h3> The PDAC model was bioprinted using a commercial bioprinter. A novel bioink composition which mimics the complex PDAC tumor microenvironment was used to create the tumor model. Various PDAC cell lines were used to create multiple models. The bioprinted tumor model was then characterized for cell viability, cell proliferation, elastography, protein changes, drug toxicity analysis. Additionally, the tumor was also assessed for its use as a tool for studying efficacy of radiotherapy. <h3>Results</h3> The bioprinted tumor model using the novel bioink showed favorable cell proliferation and viability for up to 15 days. Additionally, elastography analysis of the tumor model showed matrix stiffness similar to clinical values (Young's modulus). Our study is the first one to use shear wave elastography to evaluate matrix stiffness of a bioprinted tumor model. Considering the importance of tumor stiffness, stiffness evaluation increases the translational impact of the model for efficacy and high throughput studies. Once established, the model was used to study efficacy of irradiation at 5 and 10 Gy doses over one week. To analyze the effect of radiation, the tumor models were created using luciferase transfected cell line. After one week of irradiation, 10 Gy dosing showed significant reduction in cancer cell viability. The cell viability was studied by analyzing luminescence activity of the cancer cells. In addition to radiotherapy, the tumor models were also used to study efficacy of chemotherapies such as paclitaxel, gemcitabine etc. Further, we also added immune cells in the model to incorporate immune aspect of the tumor microenvironment. <h3>Conclusion</h3> In this study, the bioprinted PDAC model was established, optimized and characterized as a tool for radio-oncology, chemotherapy and immune modulation studies.