Development of a Bioartificial Kidney

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