Tu159 - Engineering the Prostate Cancer Microenvironment: A 3D Bioprinted Model Using Dynamic Gelatin-based Hydrogel with Laponite® for Therapeutic Studies

Ananya Aggarwal, BTech – Graduate Student, Biomedical Sciences, University of Illinois; Gnanasekar Munirathinam, PhD – Associate Professor, Biomedical Sciences, University of Illinois; Ramaswamy Kalyanasundaram, DVM, PhD – Professor, Biomedical Sciences, University of Illinois; Mohammad Alam, PhD – Biomedical Sciences – University of Illinois

Abstract Text: An ex vivo model for the prostate cancer tumor microenvironment (PCa-TME) remains elusive due to the disease’s complexity and clinical heterogeneity. Recent advancements in in vitro models, such as organoid technology and 3D bioprinting, have shown promise, but there is a need for ideal bioinks that can support cellular interactions and accurately predict drug responses. This study aimed to develop a 3D bioprinted model of PCa-TME using engineered gelatin methacrylate (GelMA)-based hydrogels enhanced with the rheology modifier Laponite®. We hypothesized that tunable viscoelastic hydrogels mimic the dynamic properties of the extracellular matrix in PCa-TME to support paracrine signaling among normal, cancer, and immune cells. The viability, proliferation, and migration of cells using dynamic GelMA-based hydrogels were investigated using standard prostate cell lines such as WPMY-1, LNCaP, DU145, and PC3, along with two cancer-induced cell lines with chronic exposure to cadmium, i.e., WPMY-Cd and BPH-Cd. Results revealed that the dynamic GelMA-based hydrogels supported the desired cellular properties in 3D bioprinted mono- and co-cultures of normal and cancer cells. Bioprinted structures with dynamic GelMA bioinks had improved printability, shape fidelity retention, and interconnected porosity. The live/dead assay showed a significantly higher number of dead cells than live cells (p-value < 0.001) in the 3D bioprinted PCa-TME model after 5 days of treatment with a drug candidate, 1,4-dihydroxy-2-naphthoic acid (DHNA). The novel 3D-bioprinted PCa-TME model is currently being evaluated for macrophage polarization and transcriptome analysis for primary and secondary metastasis.