EAGER: Colloidal Crystal Membranes for encapsulation of porcine islets

EAGER：用于封装猪胰岛的胶体晶体膜

• 批准号: 0956601
• 负责人: Michael Tsapatsis
• 金额: $ 4.8万
• 依托单位: University of Minnesota-Twin Cities
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-10-01 至 2010-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0956601&HistoricalAwards=false
• 关键词: EAGER; Colloidal; Crystal; Membranes; encapsulation

The viability of xenotransplanted cells could be dramatically improved through immunoisolation by permselective encapsulation. The ideal capsule would simultaneously protect the cell from immunological attack, transport nutrients, and release therapeutic cell metabolites (e.g., insulin). Despite recent progress, persistent challenges include the lack of fine control over pore size and encapsulation thickness, the latter leading to mass transport limitations, cell necrosis, and slow cellular response to external stimuli. Material instability and bio-incompatibility also challenge cell encapsulation. An exploratory research effort is proposed for the formation of permselective coatings on porcine pancreatic islets using silica nanoparticles. Such coatings may allow unprecedented control over thickness, pore size and active chemical functionality. The proposed work will benefit from collaborations with The Diabetes Institute at the University of Minnesota and derives from the recent identification of a benign (i.e., near-physiological conditions) and controllable means for synthesizing stable silica nanoparticles from 5 to 40 nm, and their ordering into colloidal crystal arrays and thin films. The infliction of more than twenty million Americans with diabetes motivates the proposed research which aims to realize a novel and potentially high impact solution to the challenging problem of islet xenotransplantation. The success of the proposed initiative is of direct interest to the development of novel permselective membrane materials and applications. In addition, it stands to establish fundamental understanding of nanoparticle-cell association for mass transport control, the implications of which may ultimately influence targeted drug and DNA delivery and non-invasive cellular imaging and tracking.

异种移植细胞的活力可以显着提高免疫隔离通过选择性渗透包封。理想的胶囊将同时保护细胞免受免疫攻击、运输营养物质并释放治疗性细胞代谢产物（例如，胰岛素）。尽管最近取得了进展，但持续的挑战包括缺乏对孔径和包封厚度的精细控制，后者导致质量运输限制、细胞坏死和对外部刺激的缓慢细胞反应。材料不稳定性和生物不相容性也对细胞包封提出了挑战。 提出了一种探索性的研究工作，用于使用二氧化硅纳米颗粒在猪胰岛上形成选择性渗透涂层。这样的涂层可以允许对厚度、孔径和活性化学功能进行前所未有的控制。拟议的工作将受益于与明尼苏达大学糖尿病研究所的合作，并源于最近对良性（即，近生理条件）和用于合成5至40 nm的稳定二氧化硅纳米颗粒的可控手段，以及它们有序化成胶体晶体阵列和薄膜。 超过2000万美国人患有糖尿病，这激发了拟议的研究，旨在为胰岛异种移植的挑战性问题实现一种新的和潜在的高影响力的解决方案。所提出的倡议的成功是直接利益的新型选择性渗透膜材料和应用的发展。此外，它还将建立对用于质量传输控制的纳米颗粒-细胞关联的基本理解，其影响可能最终影响靶向药物和DNA递送以及非侵入性细胞成像和跟踪。