Engineering a Biomimetic Glomerular Filtration Barrier: Coculturing Endothelial Podocytes on Kidney ECM-Bacterial Cellulose Membrane Hybrid.

Abstract

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