EAGER: Colloidal Crystal Membranes for encapsulation of porcine islets

经皮选择性包埋免疫隔离可显著提高异种移植细胞的存活率。理想的胶囊应该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物(如胰岛素)。尽管最近取得了进展，但持续存在的挑战包括缺乏对孔大小和包膜厚度的精细控制，后者导致质量传输受限、细胞坏死和细胞对外部刺激的反应缓慢。材料的不稳定性和生物的不兼容性也对细胞的封装提出了挑战。利用二氧化硅纳米颗粒在猪胰岛表面形成渗透选择涂层是一项探索性的研究工作。这种涂层可以实现对厚度、孔大小和活性化学功能的前所未有的控制。这项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，并源于最近确定了一种良性(即近生理条件)和可控的方法，用于合成5至40 nm的稳定二氧化硅纳米颗粒，并将它们排列成胶体晶体阵列和薄膜。两千多万美国糖尿病患者的患病促使了这项拟议的研究，该研究旨在实现一种新的、潜在的高影响力的解决方案，以解决具有挑战性的异种胰岛移植问题。该倡议的成功直接关系到新型渗透选择性膜材料和应用的发展。此外，它将建立对纳米颗粒-细胞关联用于质量传输控制的基本理解，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。

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.