A biomimetic tubuloid-on-a-chip for human renal fibrosis research and anti-fibrotic drug development.

Chronic kidney disease (CKD), driven largely by renal fibrosis, lacks effective therapies due to the limited predictive capacity of existing preclinical models. To address this, we developed a human tubuloid-on-a-chip model integrating tubuloids, endothelial cells, and immune cells within a microfluidic system to recapitulate the key pathophysiology of renal fibrosis. Induction of fibrosis with TGF-β1 in this system recapitulated key pathological features, including extracellular matrix deposition, epithelial-mesenchymal transition, and loss of epithelial polarity. Functional assessments revealed impaired tubular reabsorption, including reduced albumin uptake and glucose transport, alongside elevated oxidative stress, mirroring clinical observations in CKD patients. The model's pharmacological relevance was validated by the therapeutic effects of nintedanib, which attenuated fibrotic phenotypes. Taken together, this tubuloid-on-a-chip platform demonstrates the potential to model complex fibrotic pathologies in vitro and may serve as a useful tool for CKD research and anti-fibrotic drug development, potentially accelerating therapeutic discovery for renal fibrosis.