Renal Biology Driven Macro- and Microscale Design Strategies for Creating an Artificial Proximal Tubule Using Fiber-Based Technologies

Abstract

Chronic kidney disease affects one in six people worldwide. Due to the scarcity of donor kidneys and the complications associated with hemodialysis (HD), a cell-based bioartificial kidney (BAK) device is desired. One of the shortcomings of HD is the lack of active transport of solutes that would normally be performed by membrane transporters in kidney epithelial cells. Specifically, proximal tubule (PT) epithelial cells play a major role in the active transport of metabolic waste products. Therefore, a BAK containing an artificial PT to actively transport solutes between the blood and the filtrate could provide major therapeutic advances. Creating such an artificial PT requires a biocompatible tubular structure which supports the adhesion and function of PT-specific epithelial cells. Ideally, this scaffold should structurally replicate the natural PT basement membrane which consists mainly of collagen fibers. Fiber-based technologies such as electrospinning are therefore especially promising for PT scaffold manufacturing. This review discusses the use of electrospinning technologies to generate an artificial PT scaffold for ex vivo/in vivo cellularization. We offer a comparison of currently available electrospinning technologies and outline the desired scaffold properties required to serve as a PT scaffold. Discussed also are the potential technologies that may converge in the future, enabling the effective and biomimetic incorporation of synthetic PTs in to BAK devices and beyond.