End-stage renal disease (ESRD) affects 378,000 Americans and is increasing in prevalence at 8% / year. Of the three treatment options (transplant, peritoneal, and hemo dialysis) none is ideal, as transplant is severely limited by scarcity of donor organs and both dialytic modalities are expensive and confer significant morbidity and mortality. Advances in the treatment of ESRD will involve the tissue engineering of nephronal units; indeed, a tissue-engineered renal tubule cell device is presently in clinical trials. For this technology to be generally applicable, devices must be compact, inexpensive, and self-monitoring. An eventual goal of this line of research is an implantable tissue engineered device for renal replacement therapy. The advent of Microelectromechanical Systems (MEMS) technology has produced practical surface and bulk micromachining techniques with the ability to manufacture mechanical devices (pores, valves, gears etc.) with feature sizes on the same order of magnitude as subcellular organelles, in combination with on-chip electronics and sensors. This combination allows MEMS devices to sense their local environment and intelligently act upon the local environment by changing electrical and mechanical properties of the devices. Preliminary testing of a MEMS ultrafilter for use in renal replacement therapy has begun, as well as definition of the biocompatibilty of MEMS materials. This project seeks to demonstrate attachment and stable growth of renal proximal tubule cells (RPTCs) on silicon and other MEMS materials.
Specific Aim 1 : Demonstrate attachment of porcine and human RPTCs to mono- and poly-crystalline silicon, silicon dioxide, silicon nitride, and polydimethoxysilane (""""""""MEMS materials""""""""), with and without extracellular matrix proteins.
Specific Aim 2 : demonstrate the RPTCs on MEMS materials are able to form stable monolayers with tight junctions.
Specific Aim 3 : demonstrate metabolic activity, includingammoniagenesis, Vitamin D hydroxylation, and glutathione metabolism by RPTCs on MEMS materials.
Specific Aim 4 : Demonstrate attachment, growth, and differentiated function of RPTCs on nanoporous substrates. This project has a high likelihood of success, and provides a necessary first step in the tissue engineering of an implantable nephronal unit. Failure of RPTCs to grow on these substrates despite a variety of suface modifications would be extremely important, as it would indicate a need for new materials in bioengineering.
| Roy, S; Goldman, K; Marchant, R et al. (2011) Implanted renal replacement for end-stage renal disease. Panminerva Med 53:155-66 |
