Microencapsulation of cells, including islets, within stable ultra-thin membranes of maleimide-conjugated PEG-lipid with multifunctional crosslinkers
Microencapsulation of cells, including islets, within stable ultra-thin membranes of maleimide-conjugated PEG-lipid with multifunctional crosslinkers
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DOI：
10.1016/j.biomaterials.2013.01.015
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发表时间：
2013-04-01
期刊：
影响因子：
14
通讯作者：
Nilsson, Bo
中科院分区：
文献类型：
--
作者：
Teramura, Yuji;Oommen, Oommen P.;Nilsson, Bo
将朗格汉斯胰岛和胰岛素分泌细胞包封在半透膜内被认为是一种安全、简单的胰岛移植技术，可以减轻早期移植物损失，避免免疫抑制治疗。然而，当胰岛和细胞被包裹在聚合物膜内时，这些植入物的总体积趋于增加，限制了被包裹细胞和周围组织之间的运输。超薄膜可以潜在地克服这些扩散限制，以提供临床应用的植入物。在这里，我们提出了一种方法，将胰岛和细胞包裹在一个稳定的超薄聚合物膜内，使用含有马来酰亚胺基团的聚乙二醇共轭磷脂（mal - peg -脂质）和多种相互作用聚合物（例如，4臂PEG-Mal和8臂PEG-SH）。当mal - peg -脂质被添加到胰岛和细胞悬浮液中时，处于平衡状态的胶束会自发地掺入细胞表面。在混合物中加入4臂PEG-Mal和8臂PEG-SH导致膜厚度大幅增加，因为许多mal - peg -脂质胶束参与了微米水平的膜形成。用这种方法微胶囊化后，胰岛体积未见明显增加。聚合物膜对胰岛的微胶囊化表现出半渗透性，即使在7天后，也不会影响胰岛素在葡萄糖刺激下的释放。胰岛和细胞周围的聚合物膜结构至少维持了30天。此外，所形成的膜在暴露于人全血和血清时表现出较低的血栓形成性和抑制补体活化。(c) 2013 Elsevier Ltd.版权所有。
The encapsulation of islets of Langerhans (islets) and insulin-secreting cells within a semi-permeable membrane has been suggested as a safe and simple technique for islet transplantation to attenuate early graft loss and avoid immunosuppressive therapy. The total volume of these implants tends, however, to increase upon encapsulation of the islets and cells within the polymer membrane, limiting transport between encapsulated cells and the surrounding tissue. Ultra-thin membranes could potentially overcome these diffusion limitations to provide for clinically applicable implants. Here we propose a method to encapsulate islets and cells within a stable ultra-thin polymer membrane using poly(ethylene glycol)-conjugated phospholipid bearing a maleimide group (Mal-PEG-lipids) and multiple interactive polymers (e.g., 4-arm PEG-Mal and 8-arm PEG-SH). When Mal-PEG-lipids were added to islet and cell suspensions, spontaneous incorporation into a cell surface occurred from the micelles at an equilibrium state. The addition of 4-arm PEG-Mal and 8-arm PEG-SH to the mixture induced a substantial increase in the membrane thickness because a number of Mal-PEG-lipid micelles were involved in the membrane formation at the micrometer level. No appreciable increase in islet volume was observed after microencapsulation by this method. Microencapsulation of islets with the polymer membranes, which showed semi-permeability, did not impair insulin release in response to glucose stimulation, even after 7 days. The polymer membrane structure surrounding the islets and cells was well maintained for at least 30 days. In addition, the membrane formed showed much lower thrombogenicity and inhibited complement activation upon exposure to human whole blood and serum. (c) 2013 Elsevier Ltd. All rights reserved.