A biomimetic in vitro glomerular filtration barrier model for investigating renal barrier dysfunction in hyperglycemia.

Hyperglycemia and hypertension are primary contributors to chronic kidney disease (CKD), typically managed by dialysis or kidney transplantation. However, these treatments often have limited efficacy and can contribute to the progression of the disease. Tissue-engineered in vitro kidney models have emerged as promising tools for enhancing the understanding of disease mechanisms and supporting the development of targeted therapies. Yet, many existing models fail to replicate the complex structural and biochemical microenvironment of the native kidney. To address this, a biomimetic diabetic in vitro glomerular filtration barrier (GFB) using kidney-derived decellularized extracellular matrix hydrogel coating on a nanofibrous bacterial cellulose (BC) membrane. This scaffold provides both architectural support and essential cues that promote the attachment and growth of endothelial and podocyte cells. The model, when exposed to hyperglycemic conditions, exhibited altered expression of renal markers, including PECAM-1, nephrin, and podocin. Additionally, the developed model was treated with metformin, a widely used prescription medication, primarily for type 2 diabetes, to mitigate hyperglycemia-induced cellular damage. Functional validation of the hyperglycemic GFB model was performed by assessing the permeability of albumin, glucose, and creatinine, which revealed increased concentrations of these molecules in the filtrate region, indicating impaired filtration function. These results highlight the model's ability to recapitulate key pathological features of diabetic nephropathy but also demonstrate its partial reversal upon therapeutic intervention, thus offering a physiologically relevant platform for studying renal disease progression and screening nephrotoxic drugs, potentially reducing the need for animal models.