NOVEL ISLET-POLYMER MATRIX SYSTEM

新型胰岛聚合物基质系统

• 批准号: 2016661
• 负责人: You Han Bae
• 金额: $ 10.85万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-01-01 至 1998-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2016661
• 关键词: acrylamides; adsorption; artificial endocrine pancreas; artificial membranes; biomaterial compatibility; biomaterial development /preparation; biomaterial evaluation; cell aggregation; chemical synthesis; copolymer I; dogs; foreign body reaction; glucose; high performance liquid chromatography; insulin; insulin dependent diabetes mellitus; laboratory rat; membrane permeability; nonhuman therapy evaluation; pancreatic islets; polymethacrylate; secretion; sulfonylurea; swine; tissue engineering; tissue support frame

This grant proposal introduces a new concept for an implantable biohybrid artificial pancreas to treat Type I Diabetes Mellitus. Among the many limited approaches attempted, the most successful data has been obtained with transplantation of immunoprotected pancreatic islets. Recognizing the limited life span of islet cells due to an abnormal living environment or in emergency, such as unexpected cell lysis, it will be necessary for the implanted to be retrieved or replaced with fresh islets. Existing systems, such as intraperitoneal grafting of encapsulated islets or intravascular grafting of islets in a housing may have severe limitations for retrieval or replacement. The proposed system consists of an islet/thermosensitive polymer matrix and an immuno-protecting membrane pouch. The thermosensitive polymer matrix undergoes phase transition from a soluble form to a precipitation when the temperature is raised beyond the lower critical solution temperature of the polymer. This allows for the injection and removal of islet suspension in the polymer solution at low temperature and solidifying around islets in the loosely structured polymer matrix at body temperature. This polymer matrix will prevent islets from aggregation in the pouch, will allow efficient diffusion of nutrients, glucose and insulin, and provide an easy method for replacement/retrieval. In addition, this grant proposes to graft sulfonylurea molecules onto thermosensitive polymer chains. This biospecific polymer will stimulate insulin secretion of beta-cells and enhance glucose response. This may offer an opportunity to minimize the number of islets implanted, thereby reducing the implant volume and increase the overall efficiency of the system. The aim of this proposal is to construct a refillable islet/polymer matrix system in a pouch, test its feasibility and optimize the system.

该赠款提案引入了一个新概念，用于植入生物杂种 人工胰腺治疗I型糖尿病。在许多人中 尝试的有限方法，获得了最成功的数据 免疫保护胰岛的移植。认识到 由于生活环境异常或 在紧急情况下，例如意外的细胞裂解，对于 植入要检索或用新鲜胰岛取代。现有系统， 例如封装胰岛的腹膜内移植或血管内 在住房中嫁接胰岛可能有严重的检索限制 或更换。所提出的系统由胰岛/热敏性系统组成 聚合物基质和免疫保护膜袋。这 热敏感聚合物基质经历了从可溶性的相变 当温度升高到下方时，形成降水 聚合物的关键溶液温度。这允许 在低的聚合物溶液中注入和去除胰岛悬浮液 温度并在胰岛周围凝固，结构松散 聚合物基质在体温下。此聚合物矩阵将阻止 袋中聚集的胰岛将有效扩散 营养素，葡萄糖和胰岛素，并为 替换/检索。此外，这笔赠款建议将移植物 磺酰脲分子到热敏聚合物链上。这 生物特异性聚合物将刺激β细胞的胰岛素分泌和 增强葡萄糖反应。这可能提供了最小化的机会 植入的胰岛数量，从而减少了植入物的体积和 提高系统的整体效率。该提议的目的是 要在袋中构建可再填充的胰岛/聚合物矩阵系统，请测试 可行性并优化系统。