BIOCOMPATIBLE MEMBRANES FOR ISLET XENOGRAFTS

将开发具有增强生物相容性的膜， 异种胰岛移植物的免疫分离， 将确定生物不相容性的机制。 在一个相对 成功的技术，膜是由凝聚的一个 聚阴离子、水溶性、无毒聚合物（褐藻胶，一种多糖）， 聚阳离子水溶性聚合物（聚赖氨酸，一种聚氨基酸）。 的 所得膜由相互包合的水凝胶组成， 相互作用的带负电和带正电的聚合物。 蛋白质吸附到 这种带电荷的膜和增强成纤维细胞粘附，扩散， 过度生长 这一过程可由炎症引发或加速 由于巨噬细胞在膜上的扩散和激活， 可以被补体刺激。 将合成一种新型聚合物，其具有聚（L-赖氨酸）（缩写为 PLL）主链与聚（环氧乙烷）（缩写为PEO）侧臂。 的 聚阳离子骨架将与褐藻胶相互作用形成水凝胶膜， 而非离子的亲水性PEO侧臂将屏蔽带电的 从生物环境中的蛋白质和细胞的表面。 的 由褐藻胶凝聚体制成的膜的渗透性和稳定性， 将在体外测量PLL-移植物-PEO。 膜渗透性将为 通过测量125 I标记的蛋白质相对于 数学模型 将通过测量来评估体外稳定性 膜形成后即刻和1个月后的渗透率 孵化 这些膜的生物相容性将在 通过测量蛋白质吸附，成纤维细胞扩散， 补体激活、巨噬细胞扩散和巨噬细胞合成 白细胞介素1。 这将有助于深入了解 这些材料的生物相容性。 将评估生物相容性 在非糖尿病仓鼠体内使用无胰岛微囊， 植入后腹腔巨噬细胞的出现， 的细胞和胶原蛋白合成的微胶囊膜，和 微囊聚集并结合到腹膜内 组织中 将通过以下方法评估胶囊的体内稳定性： 腹膜组织的组织学检查是否有破损的包膜， 植入前和植入后的渗透性测量。 大鼠胰岛将被分离，微囊化， 在糖尿病金黄仓鼠中腹膜内注射。 初步体内数据 1个月的持续时间与这些材料制成的微胶囊 并支持这些微胶囊增强了 生物相容性 用PLL-接枝-PEO材料制成的微胶囊 显示出明显少于那些制造的细胞附着和炎症 没有植入PLL

Membranes with enhanced biocompatibility will be developed for the immunoisolation of xenogenic islet of Langerhans transplants, and the mechanisms of bioincompatibility will be determined. In a relatively successful technique, a membrane is formed by the coacervation of a polyanionic, water-soluble, nontoxic polymer (algin, a polysaccharide) with a polycationic, water-soluble polymer (polylysine, a polyamino acid). The resulting membrane consists of a hydrogel of mutually entwined, closely interacting negatively and positively charged polymers. Proteins adsorb to this charged membrane and potentiate fibroblast adhesion, spreading, and overgrowth. This process may be initiated or accelerated by inflammation resulting from macrophage spreading and activation on the membrane, which may be stimulated by complement. A novel polymer will be synthesized that has a poly(L-lysine) (abbreviated PLL) backbone with poly(ethylene oxide) (abbreviated PEO) side arms. The polycationic backbone will interact with algin to form a hydrogel membrane, and the nonionic, hydrophilic, PEO side arms will shield the charged surface from the proteins and cells in the biological environment. The permeability and stability of membranes made from coacervates of algin and PLL-graft-PEO will be measured in vitro. Membrane permeance will be assessed by measuring the diffusion of 125I-labeled proteins relative to a mathematical model. Stability in vitro will be assessed by measuring permeance immediately after membrane formation and after 1 month incubation. The biocompatibility of these membranes will be assessed in vitro by measurement of protein adsorption, fibroblast spreading, complement activation, macrophage spreading, and macrophage synthesis of interleukin 1. This will provide insight into the mechanisms of bioincompatibility in these materials. Biocompatibility will be assessed in vivo with islet-free microcapsules in nondiabetic hamsters by measuring the appearance of peritoneal macrophages post-implantation, the attachment of cells to and collagen synthesis upon the microcapsule membranes, and the clumping and incorporation of the microcapsules into the peritoneal tissues. Stability of the capsules in vivo will be assessed by histological examination of peritoneal tissues for broken capsules and by measurement of permeability before implantation and after explantation. Rat islets will be isolated, microencapsulated, and the transplanted intraperitoneally in diabetic golden hamsters. Preliminary in vivo data of 1 month duration with microcapsules made from these materials are presented and lend support to the hypothesis that these microcapsules have enhanced biocompatibility. Microcapsules made with the PLL-graft-PEO material showed dramatically less cell attachment and inflammation than those made with ungrafted PLL.