Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore.
Biomaterials. 2011 Feb;32(6):1465-76. doi: 10.1016/j.biomaterials.2010.10.061. Epub 2010 Dec 9.
The bioreactor unit of bioartificial kidneys contains porous membranes seeded with renal cells. For clinical applications, it is mandatory that human primary renal proximal tubule cells (HPTCs) form differentiated epithelia on the membranes. Here, we show that HPTCs do not grow and survive on a variety of polymeric membrane materials. This applies also to membranes consisting of polysulfone/polyvinylpyrrolidone (PSF/PVP), which have been used in the bioreactor unit of bioartificial kidneys after coating with an extracellular matrix (ECM). Our data reveal that coating with just an ECM does not sufficiently improve HPTC performance on non-HPTC-compatible membrane materials. On the other hand, we have characterized the effects of a variety of surface treatments and coatings, and found that double coating with 3,4-dihydroxy-l-phenylalanine and an ECM markedly improves HPTC performance and results in the formation of differentiated epithelia on PSF/PVP membranes. We have also synthesized alternative membrane materials, and characterized membranes consisting of polysulfone and Fullcure. We found that these membranes sustain proper HPTC performance without the need for surface treatments or coatings. Together, our data reveal that the materials that have been previously applied in bioartificial kidneys are not suitable for applications with HPTCs. This study elucidates the types of membrane materials and coatings that are favorable for the bioreactor unit of bioartificial kidneys.
生物人工肾的生物反应器单元包含接种有肾细胞的多孔膜。对于临床应用,必须使人类原代肾近端小管细胞 (HPTC) 在膜上形成分化的上皮。在这里,我们表明 HPTC 不会在各种聚合物膜材料上生长和存活。这同样适用于用细胞外基质 (ECM) 涂层后的由聚砜/聚乙烯吡咯烷酮 (PSF/PVP) 组成的膜,其已被用于生物人工肾的生物反应器单元。我们的数据表明,仅用 ECM 涂层并不能充分提高 HPTC 在非 HPTC 兼容的膜材料上的性能。另一方面,我们已经对各种表面处理和涂层的效果进行了表征,发现用 3,4-二羟基-L-苯丙氨酸和 ECM 双重涂层可显著改善 HPTC 的性能,并导致在 PSF/PVP 膜上形成分化的上皮。我们还合成了替代的膜材料,并对由聚砜和 Fullcure 组成的膜进行了表征。我们发现这些膜在不需要表面处理或涂层的情况下即可维持适当的 HPTC 性能。总之,我们的数据表明,先前在生物人工肾中应用的材料不适合与 HPTC 一起应用。本研究阐明了有利于生物人工肾生物反应器单元的膜材料和涂层类型。