Combining Microfluidic Assessment with Encoded Hydrogel Microparticle-Based Immunoassay for Anti-Interleukin Drug Repurposing of Pulmonary Fibrosis Therapy.

Abstract

Pulmonary fibrosis is a life-threatening disorder characterized by excessive extracellular matrix (ECM) deposition and progressive dysfunction. The disease progression is closely associated with increased ECM stiffness, which compromises normal tissue mechanics and leads to respiratory failure. Although its etiology is multifactorial, immune-mediated responses are central drivers of fibrotic remodeling through inflammatory cytokine release and aberrant tissue repair. Here, we present a microfluidic-integrated 3D immune spheroid platform for pulmonary fibrosis remodeling, featuring cytokine-secreting immune cells to induce fibrosis-like alterations in mechanical properties. This platform enables quantitative analysis of reversible changes in ECM stiffening and its modulation upon anti-interleukin drug administration using microfluidic mechanical assessment. Simultaneously, cytokine secretion profiles are obtained via multiplex immunoassays. Treatment with anti-interleukin agents elicited target-specific reductions in both spheroid stiffness and pro-inflammatory cytokine output. This integrated approach offers a screening-compatible preclinical tool to dissect immune-driven fibrotic dynamics and identify mechanically restorative antifibrotic therapies, highlighting the therapeutic repurposing potential of anti-interleukin drugs.