Diffusion characteristics of microfabricated silicon nanopore membranes as immunoisolation membranes for use in cellular therapeutics.

Diffusion characteristics of microfabricated silicon nanopore membranes as immunoisolation membranes for use in cellular therapeutics.
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微加工硅纳米孔膜作为免疫隔离膜用于细胞治疗的扩散特性。

DOI:
10.1089/dia.2005.7.151
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发表时间:
2005
影响因子:
5.4
通讯作者:
Rampersaud,ArfaanA
Rampersaud,ArfaanA
中科院分区:
医学3区
文献类型:
--
作者:
Smith,Catherine;Kirk,Randy;West,Teri;Bratzel,Marsha;Cohen,Michael;Martin,Francis;Boiarski,Anthony;Rampersaud,ArfaanA

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目的:免疫隔离膜通过物理隔离异种移植组织与宿主,保护异种移植组织。然而,大多数是商业过滤膜,不具备免疫隔离所需的所有功能。硅纳米孔膜是含有数万个纳米尺寸通道的薄层硅,其允许小分子的被动扩散。他们是优秀的尺寸选择性屏障,本研究的目的是进一步表征其免疫保护性能,并与商业filtermembranes.Methods比较:跨膜扩散进行了研究,使用不同大小的分子,包括荧光素异硫氰酸酯-葡聚糖(相对分子大小为4.4 kDa,20 kDa,和70 kDa),葡萄糖(0.18 kDa),胰岛素(6.1 kDa),和免疫球蛋白G(IgG)(150 kDa)。通过溶血测定分析对补体介导的裂解的保护。用已报道的免疫隔离屏障滤膜进行了比较研究。为了评估硅纳米孔膜是否改变葡萄糖刺激的胰岛的胰岛素反应模式,macrocapsules构建与纳米孔膜和填充与胰岛,和动态灌注studies were performed.Results:相对于商业膜,硅纳米孔膜显示出高速率的葡萄糖和胰岛素的扩散,并作为有效的屏障补体蛋白和IgG。没有其他商业膜表现出可比的扩散和免疫隔离性能。放置在macrocapsule内的胰岛表现出葡萄糖响应性胰岛素分泌在perfusion study.Conclusions:硅纳米孔膜具有独特的和理想的扩散性能作为免疫隔离膜,并允许快速响应时间的刺激胰岛葡萄糖。这些特征归因于膜的物理性质,即直通道、足够的孔隙率和5 μm的厚度。
Objective:Immunoisolating membranes protect transplanted xenogeneic tissue by physically isolating them from the host. However, most are commercial filter membranes that do not possess all the features needed for immunoisolation. Silicon nanopore membranes are thin layers of silicon containing tens of thousands of nanometer-sized channels, which allow passive diffusion of small molecules. They are excellent size-selective barriers, and the objective of this study was to further characterize their immunoprotective properties and make comparisons with commercial filter membranes.Methods:Diffusion across membranes was studied using molecules of different sizes, including fluorescein isothiocyanate-dextrans (relative molecular sizes of 4.4 kDa, 20 kDa, and 70 kDa), glucose (0.18 kDa), insulin (6.1 kDa), and immunoglobulin G (IgG) (150 kDa). Protection from complement-mediated lysis was analyzed by a hemolysis assay. Comparative studies were done with filter membranes that have been reported as immunoisolation barriers. To evaluate if silicon nanopore membranes changed insulin response patterns for glucose-stimulated islets, macrocapsules were constructed with nanopore membranes and filled with pancreatic islets, and dynamic perifusion studies were performed.Results:Relative to commercial membranes, silicon nanopore membranes showed high rates of diffusion for glucose and insulin, and acted as efficient barriers to complement proteins and IgG. No other commercial membrane showed comparable diffusion and immunoisolating properties. Islets placed within the macrocapsule exhibited glucose-responsive insulin secretion in perifusion studies.Conclusions:Silicon nanopore membranes possess unique and desirable diffusion properties as immunoisolation membranes and allow rapid response times for the stimulation of islets by glucose. These features are attributed to the physical properties of the membranes, namely, the straight channels, adequate porosity, and the 5 µm thickness.