Human proximal tubule cells (HPTCs) play a crucial role in the development of bioartificial kidneys. It is essential that these cells be able to form epithelia on the porous membrane of the device, creating a ‘bioreactor’ that performs many of the functions a healthy kidney would normally perform. Unfortunately, the lack of biocompatible porous membranes that can promote the differentiation of HPTCs into epithelia has hindered the development of bioartificial kidneys.
A research team led by Daniele Zink and Jackie Y. Ying at the A*STAR Institute of Bioengineering and Nanotechnology has now developed membrane materials and coatings that are suitable for HPTC growth and differentiation by modifying the surface of established materials and synthesizing novel materials1.
Preliminary assessments showed that the polymeric membranes currently used in commercial hollow fiber-based hemodialysis cartridges, including membranes consisting of polyethersulfone (PES) or polysulfone (PSF) mixed with polyvinylpyrrolidone (PVP), were incompatible with HPTC growth and survival. Surface treatments and coatings using extracellular matrices also fail to significantly improve the cell performance of these conventional membranes, which is critical in bioartificial kidneys.
First, the researchers altered the surface wettability of conventional membranes through various physical and chemical treatments. Deposition of a strongly adhesive, mussel protein-derived substance known as dihydroxyphenylalanine (DOPA) boosted the hydrophilicity of PES–PVP and PSF–PVP membranes, altered the density of functional surface groups, and resulted in improved cell attachment.
Next, the researchers investigated the ability of the DOPA-coated membranes to induce cell proliferation and found that, after a slight decrease in number, the HPTCs grew exponentially. On the other hand, the formation of differentiated epithelia only took place when the DOPA film was combined with another layer of collagen. “Currently, it is not understood why DOPA improves cell performance so profoundly,” says Zink. Noting that this phenomenon also occurred for other cell types, she adds that these coatings could be useful for other applications in tissue engineering.
Moreover, the HPTCs generated epithelial tissues on pure PSF and PES membranes, even without coatings. The researchers think that this is probably due to a PVP-induced suppression of the ability of the membrane to adsorb serum proteins present in the cell culture medium. The researchers also synthesized new PVP-free sponge-like membrane materials, such as polysulfone–Fullcure, that were compatible with HPTCs.
The researchers are currently pursuing the development of bioartificial kidneys. “We are proceeding with pre-clinical studies on our device,” says Zink. They are also designing instruments that deliver specific growth factors to patients with acute and chronic kidney diseases.
The A*STAR-affiliated researchers contributing to this research are from the Institute of Bioengineering and Nanotechnology