Miniaturizing the extracorporeal Renal Assist Device
The implantable bioartificial kidney builds upon the existing extracorporeal Renal Assist Device (RAD), which is a bioartificial kidney that combines a membrane hemofilter and a bioreactor of human renal tubule cells to mimic many of the metabolic, endocrine, and immunological functions of a healthy kidney.
While clinical trials confirmed that the RAD can safely treat acute renal failure in a critical care setting, adoption of the RAD for routine treatment of ESRD patients is hampered by its labor-intensive and complex operation, large size, and high marginal cost.
The ultimate goal of The Kidney Project is to apply microelectromechanical systems (MEMS) and nanotechnology to miniaturize the extracorporeal RAD into a surgically implantable, self-monitoring, and self-regulating bioartificial kidney.
After a single surgery to establish a permanent blood connection, the bioartificial kidney processes blood continuously for 24 hours per day, which mitigates the inconveniences and morbidities associated with intermittent hemodialysis.
There are several benefits to the implantable bioartificial kidney including the alleviation of the necessity of constant physician oversight and a heavy regimen of immunosuppressant drugs and medication.
Leveraging recent advances in science
To mimic the work of a natural kidney, the bioartificial kidney has to contain high efficiency ultrafiltration membranes, be able to regulate blood flow, and stabilize necessary cells within an engineered environment.
Three key technology developments were needed to implement these functions:
- high-efficiency ultrafiltration membranes
- control of blood-materials interactions such as thrombosis and fouling
- stable differentiated function of renal cells in an engineered construct
Advances in silicon nanotechnology were required to make it possible to mass-produce reliable, high-porosity, robust, and compact membranes. Improvements in molecular coatings that impart blood compatibility and techniques to coat silicon membranes without blocking pores were needed. And cell sourcing and storage issues had to be resolved. All of these technologies are now in place.
Two components: hemofilter and cell bioreactor
Our hemofilter uses silicon nanotechnology to produce a highly efficient and compact membrane, which relies on the body’s blood pressure to perform filtration without needing pumps or a power supply. The hemofilter must be capable of generating meaningful ultrafiltration volumes at driving pressures similar to capillary perfusion pressure, while remaining free of fouling for months. Furthermore, if this technology is to be generalized to implantable continuous therapies, protein losses must be minimal.
For the cell bioreactor, we are applying recent advances in the field of tissue engineering to grow and maintain renal tubule cells. The bioreactor must be capable of high-volume salt and water reabsorption from the ultrafiltrate while maintaining a barrier to reabsorption of toxins. In addition, it should impart biological activity such as autoregulation of blood pressure and production of vitamin D.
Early in our design process we identified two major obstacles to miniaturizing the RAD:
- size and pump requirements of modern dialysis units
- water volume needed for dialysis
At the same time, we were inspired by the success of hollow fiber polymer membranes used in treating renal failure excorporally. However, we noticed that the kidney’s natural fibers were uniform, elongated, slit-shaped structures, rather than the irregular and more cylindrically-shaped pores of polymer membranes. Our team has applied MEMS technology, which is often not used for biomedical applications, for the production of silicon nanopore membranes with slit-shaped pores that are tailored for implementation in a bioartificial kidney.