Engineering a Biomimetic\nGlomerular Filtration Barrier:\nCoculturing Endothelial Podocytes on Kidney ECM-Bacterial Cellulose\nMembrane Hybrid

A novel avenue for advancing our understanding of kidney\ndisease\nmechanisms and developing targeted therapeutics lies in overcoming\nthe limitations of the existing <i>in vitro</i> models.\nTraditional animal models, while useful, do not fully capture the\nintricacies of human kidney physiology and pathophysiology. Tissue\nengineering offers a promising solution, yet current models often\nfall short in replicating the complex microarchitecture and biochemical\nmilieu of the kidney. To address this challenge, we propose the development\nof a sophisticated <i>in vitro</i> glomerular filtration\nbarrier (GFB) utilizing advanced biomaterials and a kidney decellularized\nextracellular matrix (kdECM). In our approach, we employ a bacterial\ncellulose membrane (BC) as a scaffold, providing a robust framework\nfor cell growth and interaction. Coating this scaffold with kdECM\nhydrogel derived from caprine kidney tissue via a detergent-free decellularization\nmethod ensures the preservation of vital extracellular matrix proteins\ncrucial for cellular compatibility and signaling. Our engineered GFB\nnot only supports the growth of endothelial and podocyte cells but\nalso exhibits the presence of key markers such as CD31 and nephrin,\nindicating successful cellular integration. Furthermore, the expression\nof collagen IV, an essential extracellular matrix (ECM) protein, validates\nthe fidelity of our model in simulating cellular interactions within\na kdECM matrix. Additionally, we assessed the filtration efficiency\nof the developed GFB model using albumin, a standard protein, to evaluate\nits performance under conditions that closely mimic the native physiological\nenvironment. This innovative approach, which faithfully recapitulates\nthe native microenvironment of the glomerulus, holds immense promise\nfor elucidating kidney disease mechanisms, conducting permeability\nstudies, and advancing personalized therapeutic strategies. By leveraging\ncutting-edge biomaterials and tissue-specific coculture technology,\nthis study can be further extended to develop GFB for the treatment\nof renal diseases, ultimately improving patient outcomes and quality\nof life.