Abstract 1232: A 3D bioprinted prostate cancer ex vivo model with nanoengineered hydrogel for potential drug screening

Abstract Prostate cancer (PCa) is one of the most lethal cancers in men worldwide. As of 2024 there have been 2,001,140 new cases reported. The tumor microenvironment (TME) is a dynamic niche where tumor cells, stromal, and immune cell types interact within the tumor-specific extracellular matrix (ECM), playing a fundamental role in regulating tumorigenesis and dissemination. TME promotes signaling between tumor cells and non-malignant cells, which leads to tumorigenesis that results in metastasis. An Ex vivo model is required for understanding the tumor microenvironment and to study the changes that occur during metastasis but it remains challenging to achieve due to the complexity posed by the disease’s heterogeneity. Currently, the latest advancement in 3D bioprinting and organoid technology offers to fabricate a physiologically relevant ex-vivo cancer model. However, challenges remain in terms of the choice of suitable bioink. In this study, we developed a nanoengineered hydrogel (NOEH) by mixing different ratios of Laponite with Gelatin Methacrylate (GelMA). After mixing, we characterized the rheological and swelling ratio, parameters. We observed that the viscoelastic property of Nanoengineered hydrogel (NOEH) gets enhanced as the ratio of laponite. To analyze the biocompatibility and proliferation of NOEH, we embedded the prostate cancer cells (WPMY-1 and PC3), mesenchymal cells (WPMY-1), and Human umbilical vein endothelial cells (HUVECs) and observed NOEH are compatible with all the cells. We optimized the printing parameter of NOEH to fabricate the 3D prostate cancer scaffold and mimic the TME by adding different proportions of cells. The outcome of the study revealed that the NOEH supports cellular properties like viability, migration, and proliferation in 3D bioprinted scaffolds. The combination of Laponite with GelMA enhances viscoelastic properties and swelling capacity, promoting cellular interactions for the co-culture of normal and cancer cells of PCa-TME. The combination of GelMA-Laponite also resulted in higher viability as the cell in co-culture maintained high viability for 10 days. This novel 3D-bio printed PCa-TME model is progressing towards a platform for drug testing personalized medicine but needs further analysis to understand complex interactions of the cellular and non-cellular components. The PCa-TME model is being utilized to explore how the stiffening of the Extracellular Matrix contributes to chemoresistance and the potential role of efflux pumps in this process. Citation Format: Anirud Chakravarthi Arava, Camar Ameril, Ananya Aggarwal, Gnanasekar Munirathinam, Mohammad Fazle Alam. A 3D bioprinted prostate cancer ex vivo model with nanoengineered hydrogel for potential drug screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1232.