DEVELOPMENT OF A BIOARTIFICIAL KIDNEY

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Long term ex vivo therapy for kidney failure has been achieved, so that the kidney may be the first solid organ in which tissue engineering concepts can produce an implantable device for long-term in vivo replacement therapy. To replace the kidney's excretory function, an implantable bioartificial kidney requires both a device to replace blood ultrafiltration performed by renal glomeruli and a device to replace transport regulatory function of the renal tubule. We have developed early prototypic devices capable of these functions. The Phase I efforts will consolidate these efforts by identifying the best combination of synthetic materials, biologic compounds and cell components to produce an implantable bioartificial kidney. A bioartificial glomerulus will be produced using two different approaches. One approach is to promote targeted angiogenesis with the use of angiogenic factors to promote capillary growth around polysulfone hollow fibers with high hydraulic permeability but with a high reflection coefficient for proteins greater than 25,000 daltons. A second approach is to promote confluent growth in bioreactors of autologous endothelial cell monolayers along the inner surface of polysulfone hollow fibers. Experiments are planned to test the functional capacity of these two approaches to replace renal filtration. The ultimate goal of this proposal is to develop the initial functioning prototypes of an implantable bioartificial kidney containing a filtration device connected to a tubule processing unit. This Phase I grant will develop a critical foundation for the Phase II grant which will develop an implantable device to replace renal function in patients with end stage renal disease to circumvent the need for long-term dialytic therapy or renal transplantation.