008 | A 3D bioprinted microfluidic Breast Cancer-on-Chip model for studying drug transport and resistance

Simona Campora¹, Kimia Abedi², Alessandra Lo Cicero¹, Gabriele Lo Buglio¹, Francesco La Monica¹, Giulia Palazzo¹, Riccardo Barrile², Giulio Ghersi^1|4 | ¹Department of Biological, Chemical and Pharmaceutical Sciences and Technologies STEBICEF, University of Palermo, Italy; ²Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH, United States; ³Center for Stem Cells and Organoid Medicine CuSTOM, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States; ⁴Abiel Srl, Palermo, Italy.

Understanding the complex interactions among tumor cells, stromal components, and vascular networks is essential for the development of effective therapeutic strategies in breast cancer. However, conventional experimental models often fail to reproduce the physiological complexity required to reliably predict drug responses. To address these limitations, a 3D bioprinted microfluidic Breast Cancer-on-Chip platform was developed, incorporating a perfusable, endothelialized microfluidic channel that enables controlled delivery of culture medium and chemotherapeutic agents, thereby mimicking systemic drug administration [1]. The platform integrates patient-derived tumoral constructs generated through 3D bioprinting of self-assembling organoids composed of primary breast cancer epithelial cells, fibroblasts, and endothelial cells. Within this system, cells autonomously organize into structured tumoral assembloids and establish a functional microvascular network capable of invading the surrounding extracellular matrix, recapitulating key features of the tumor microenvironment. Notably, the formation of a dense, collagen-rich capsule surrounding the tumoral assembloids was observed, which appears to hinder the penetration of circulating therapeutics and may contribute to drug resistance. Targeting this endogenous collagen barrier emerges as a promising strategy to enhance intratumoral drug delivery, particularly for nanoparticle-based therapeutic systems. Disruption or modulation of collagen deposition was found to improve therapeutic penetration, potentially increasing the efficacy of both conventional chemotherapeutics and nanomedicine-based formulations. Overall, this Breast Cancer-on-Chip platform represents a versatile and physiologically relevant model for investigating tumor–stroma–vasculature interactions, elucidating mechanisms of drug resistance, and evaluating novel therapeutic approaches within a controlled microfluidic environment.