Fibrosis Drug Efficacy Assessment Based on Microfluidic Mechanical Property Evaluation of Spheroid Models

A microfluidic system is developed to evaluate fibrosis drug efficacy based on the mechanical properties of 3D spheroid models. Pulmonary fibrosis progression is mimicked by activating fibroblasts with TGF-β at different stages, and drug effects are assessed through changes in spheroid deformability. This mechanobiology-based approach provides a novel platform for fibrosis drug screening.

Abstract

Fibrotic diseases, such as pulmonary fibrosis, pose significant challenges in both research and treatment. To address the limitations of existing systems, a novel collision-based spheroid mechanical property assessment system is developed. The system utilizes inertial fluid dynamics to induce controlled collisions through uniformly sized spheroids, allowing strain to be measured via high-speed cameras. In this study, the system is first validated using HEK293T spheroids to optimize flow velocity, followed by an analysis of deformability differences between two cell types related to pulmonary fibrosis (Calu-1 and MRC-5). A co-culture spheroid model comprising two types of lung cells, endothelial and fibroblast cells, in different rations is further developed, and significant differences in deformability depending on the cell composition is observed. Finally, spheroids are treated with TGF-β1(Transforming Growth Factor-β1), a factor known to activate fibroblast cells and induce excessive extra cellular matrix (ECM) accumulation, and Nintedanib, an anti-fibrotic drug, to assess changes in mechanical properties. These results effectively reflect the mechanical properties driven by cell-cell and cell-ECM interactions and highlight the correlation between spheroid mechanics and the progression of fibrotic disease. This system not only contributes to a deeper understanding of fibrosis progression but also serves as a powerful platform for accelerating the development of anti-fibrotic therapies.