Self Assembled Polymer Scaffolds for Liver Mimics

用于肝脏模拟物的自组装聚合物支架

• 批准号: 0907590
• 负责人: Padmavathy Rajagopalan
• 金额: $ 36.5万
• 依托单位: Virginia Polytechnic Institute and State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0907590&HistoricalAwards=false
• 关键词: Self; Assembled; Polymer; Scaffolds; Liver

ID: MPS/DMR/BMAT(7623) 0907590 PI: Rajagopalan, Padmavathy ORG: Virginia TechTitle: Self Assembled Polymer Scaffolds for Liver MimicsINTELLECTUAL MERIT: This proposal describes the development of liver-mimetic cellular architectures using self-assembled polymeric scaffolds. There is currently no generally applicable methodology to layer liver cells in vitro. Although two dimensional (2D) cell cultures and co-cultures are used extensively as model systems, they do not recapitulate key spatial, geometric, and physiological characteristics of cellular architectures found in vivo. The specific features of this proposal are the design of detachable polyelectrolyte multilayer (PEM) films, the ability to incorporate cell-adhesive ligands such as galactose, tuning the physical properties of the scaffold, and the design of nanoporous detachable polyelectrolyte multilayer films. The specific objectives of the proposal are: (1) Design detachable chitosan/hyaluronan PEM films and demonstrate the feasibility of using them to assemble highly functional 3D liver-mimetic cellular architectures. (2) Tune PEM scaffold film properties to control cell growth and function. (3) Design and assemble nanoporous PEM scaffolds with tunable porosity for efficient transport of nutrients and metabolites. Such liver-mimetic tissues can serve as an accurate model for applications in bioreactor devices, understanding disease pathogenesis, toxicity evaluations, and in the testing of pharmaceuticals and drugs. The detachable PEM-scaffold can be modified, both chemically, and physically to incorporate a diverse range of cell types. BROADER IMPACTS: Hepatocyte tissue culture has challenged the regenerative medicine field for some time. This proposal holds promise for facilitating a range of investigations of liver pathogenesis, toxicity, and, ultimately, liver-like bioreactor devices. The PI and Co-PI are both active participants in outreach and educational initiatives on the Virginia Tech campus. The PI will continue to participate in the VT STARS program, a 3-year residential program focusing on low-income, under-represented youth from South West Virginia, and she has just completed a term as Chair of the AIChE Women's Initiative Committee. The proposal also details her outreach to female middle and high school students designed to acquaint them with career opportunities in science and engineering. The Co-PI is a long time participant in the VT Summer Undergraduate Research Program supported by NSF REU and IGERT awards. Continued commitment to these and other educational initiatives can be anticipated.

ID：MPS/DMR/BMAT（7623）0907590 PI：Rajagopalan，Padmavathy ORG：弗吉尼亚州技术职称：自组装聚合物支架用于肝脏模拟智能优点：该提案描述了使用自组装聚合物支架的肝脏模拟细胞结构的发展。目前还没有普遍适用的方法来体外培养肝细胞。尽管二维（2D）细胞培养物和共培养物被广泛用作模型系统，但它们不能概括体内发现的细胞结构的关键空间、几何和生理特征。 该提案的具体特征是可分离聚电解质多层（PEM）膜的设计、掺入半乳糖等细胞粘附配体的能力、调整支架的物理性质以及纳米多孔可分离聚电解质多层膜的设计。本研究的具体目标是：（1）设计可分离的壳聚糖/透明质酸PEM膜，并证明使用它们组装高功能的三维模拟肝脏细胞结构的可行性。(2)调整PEM支架膜的特性以控制细胞生长和功能。(3)设计和组装具有可调孔隙率的纳米多孔PEM支架，用于营养物质和代谢物的有效运输。这种肝脏模拟组织可以作为一个精确的模型，用于生物反应器装置的应用，了解疾病的发病机制，毒性评估，并在药物和药物的测试。可分离的PEM支架可以进行化学和物理修饰，以掺入多种细胞类型。更广泛的影响：肝细胞组织培养已经挑战了再生医学领域一段时间。 这一提议有望促进一系列肝脏发病机制，毒性，并最终，肝样生物反应器装置的调查。 PI和Co-PI都积极参与弗吉尼亚理工大学校园的外展和教育活动。 PI将继续参加VT STARS方案，这是一个为期3年的居住方案，重点是来自西南弗吉尼亚州的低收入、代表性不足的青年，她刚刚完成了AIChE妇女倡议委员会主席的任期。 该提案还详细介绍了她对女中学生和高中生的宣传，旨在让她们了解科学和工程方面的职业机会。 合作PI是由NSF REU和IGERT奖项支持的VT夏季本科生研究计划的长期参与者。 预计将继续致力于这些和其他教育倡议。