Islet-encapsulation in ultra-thin layer-by-layer membranes of poly(vinyl alcohol) anchored to poly(ethylene glycol)-lipids in the cell membrane
Islet-encapsulation in ultra-thin layer-by-layer membranes of poly(vinyl alcohol) anchored to poly(ethylene glycol)-lipids in the cell membrane
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DOI：
10.1016/j.biomaterials.2007.07.050
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发表时间：
2007-11-01
期刊：
影响因子：
14
通讯作者：
Iwata, Hiroo
中科院分区：
文献类型：
--
作者：
Teramura, Yuji;Kaneda, Yoshihiro;Iwata, Hiroo
将朗格汉斯岛（胰岛）微囊化在半透膜中，即生物人工胰腺的创建，已被研究为一种安全且简单的胰岛移植技术，无需免疫抑制治疗。将胰岛封闭在半透膜中后，植入物的总体积趋于增加，这限制了移植部位。因此，临床应用需要超薄膜。在这里，我们提出了一种新方法，将胰岛封装在聚（乙烯醇）（PVA）超薄膜中，该超薄膜锚定在胰岛细胞膜中带有马来酰亚胺基团（Mal-PEG-脂质，PEG Mw：5000）的聚（乙二醇）（PEG）-磷脂缀合物上。当将 Mal-PEG-脂质添加到胰岛悬浮液中时，它们会自发地在胰岛外层细胞上形成薄层。胰岛上的 PEG-脂质层被 PVA 单层覆盖，并通过硫醇/二硫化物交换反应的逐层方法进一步增强 PVA 膜。通过该方法进行微囊化后，没有观察到胰岛的实际体积增加。此外，将胰岛表面封装在 PVA 膜中不会损害响应葡萄糖刺激的胰岛素释放。(c) 2007 Elsevier Ltd. 保留所有权利。
The microencapsulation of islets of Langerhans (islets) in a semipermeable membrane, i.e., the creation of a bioartificial pancreas, has been studied as a safe and simple technique for islet transplantation without the need for immunosuppressive therapy. The total volume of the implant tends to increase after enclosure of the islets in the semipermeable membrane, which limits transplantation sites. Thus, ultra-thin membranes are required for clinical applications. Here, we propose a novel method to encapsulate islets in an ultra-thin membrane of poly(vinyl alcohol) (PVA) anchored to a poly(ethylene glycol) (PEG)-phospholipid conjugate bearing a maleimide group (Mal-PEG-lipids, PEG Mw: 5000) in the cell membranes of islets. When Mal-PEG-lipids were added to an islet suspension, they spontaneously formed a thin layer on cells of the outer layer of islets. The PEG-lipid layer on the islets was covered by a PVA monolayer, and the PVA membrane was further reinforced by using the layer-by-layer method with thiol/disulfide exchange reactions. No practical volume increase in islets was observed after microencapsulation by this method. In addition, encapsulation of the islet surface in PVA membranes did not impair insulin release in response to glucose stimulation.(c) 2007 Elsevier Ltd. All rights reserved.