Biosynthetic Tubules: Multiscale Approaches to Kidney Engineering

Abstract

There are over 700,000 cases of end-stage renal disease in the USA, resulting in more deaths per year than prostate or breast cancer. Many researchers have proposed the generation of in vitro kidney models or implantable therapeutic replacements using biomedical engineering strategies. Because the functional unit of the kidney—the nephron—is based on tubule structures, the formation of biosynthetic tubules is at the foundation of creating models or devices to recapitulate the kidney. Recent approaches to engineering kidney tubules involve both bioengineering (perfusable microfluidic proximal tubule chips, biomaterials as scaffolds to support engineered kidney tissue units) and biological (cellular aggregates differentiated from stem cells, self-assembled kidney tubule-like structures from epithelial cells) to model kidney cells and tissues. In this review, we detail advances in the two main approaches—bioengineering and biological—for the generation of biosynthetic kidney tubules. Although many steps have been taken towards recapitulation of kidney function, no approach has been able to recreate multiple segments of the nephron in a functional scheme.