Investigating Renal Reabsorption Physiology in 3D-Printed Human Kidney Tissues Dialysis significantly extends life for patients with end stage renal disease. However, some classify dialysis as a disease in itself, which leads to anemia, hypertension, depression, and other medical complications. It has been suggested that many of these shortcomings can be significantly improved if the current thrice-weekly intermittent therapy could be replaced with a continuous dialysis strategy, such as a wearable or implantable artificial kidney. To achieve this goal, several labs have been working toward building mechanical or biological devices that assist renal functions. While the mechanical approach is conceptually simple, it lacks biological functionality beyond filtration and usually has limited capacity for reabsorption ? a major kidney function that is often overlooked. In this research plan, by combining 3D bioprinting, kidney biology, and renal physiology, we propose to 3D-print a vascularized proximal tubule model that exhibits renal reabsorption at the macroscopic scale. Specifically, we will determine how the combination of physical cues and vasculature enhances the cell behavior of proximal tubule epithelial cells leading to an improved tissue-level reabsorption. Detailed assays that characterize the cell gene expression, phenotype, and transport-related activities will be performed. In addition, we aim to conduct a series of physiological tests quantifying the transport of sodium, water, glucose, and albumin in our 3D-printed proximal tubule tissue. Overall, our project establishes an innovative platform for conducting renal physiology experiments in in vitro human renal tissues. Ultimately, our results will provide foundational step toward to building extracorporeal living medical devices for replacing reabsorptive kidney functions. While conducting my research, I will be mentored by my postdoctoral advisor Dr. Jennifer Lewis, who is a highly regarded expert in 3D bioprinting, and will initiate collaboration with Drs. Ryuji Morizane and Lisa Satlin, who are pioneers of renal regenerative medicine and highly recognized leading renal physiologists.
The aims of this proposal are carefully crafted to leverage my expertise in physical science and material science, while simultaneously cultivating a program of hands-on experience and training in organ engineering. My strategy allows me to make immediate contributions while simultaneously investing in a knowledge base for a long-term research career in constructing living organs. Overall, I am excited to tackle the challenge of replacing dialysis. Modern day dialysis uses the same core technology that was invented 50 years ago; it is time to make significant progress forward for patients who suffer through dialysis, and I have assembled an expert team to help mentor me in this foundational research goal.
Current dialysis treatment suffers from many serious issues including significant reduction of life quality, hypertension, and many medication needs, all of which can be significantly mitigated if we could replace this thrice- weekly intermittent therapy with a continuous dialysis strategy. Working toward this goal, we plan to 3D print human renal tissue that recapitulates the continuous and active reabsorption function of human kidneys. Our 3D- printed human models will enable us to directly study human renal physiology that have only been analogously carried out using animal models, and will provide a foundational step toward replacing the current dialysis treatment and, ultimately, artificial-kidney transplantation.
