Self Assembled Polymer Scaffolds for Liver Mimics

ID: MPS/DMR/BMAT(7623) 0907590 PI: Rajagopalan， Padmavathy ORG: Virginia技术标题：用于肝脏模拟的自组装聚合物支架智力优势：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。目前尚无普遍适用的肝细胞体外分层方法。尽管二维（2D）细胞培养和共培养被广泛用作模型系统，但它们并不能概括体内细胞结构的关键空间、几何和生理特征。该方案的具体特点是设计可拆卸的聚电解质多层（PEM）薄膜，结合细胞粘附配体（如半乳糖）的能力，调整支架的物理性质，以及设计纳米多孔可拆卸的聚电解质多层薄膜。该提案的具体目标是：(1)设计可拆卸的壳聚糖/透明质酸PEM薄膜，并证明使用它们组装高功能的3D模拟肝脏细胞结构的可行性。(2)调节PEM支架膜性能，控制细胞生长和功能。(3)设计和组装具有可调节孔隙度的纳米多孔PEM支架，以有效运输营养物质和代谢物。这种肝脏模拟组织可以作为生物反应器装置、了解疾病发病机制、毒性评估以及药物和药物测试中的精确模型。可拆卸的pem支架可以进行化学和物理修饰，以纳入多种细胞类型。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。这一提议有望促进肝脏发病机制、毒性以及最终肝样生物反应器装置的一系列研究。PI和Co-PI都是弗吉尼亚理工大学校园外展和教育活动的积极参与者。PI将继续参加VT STARS项目，这是一个为期三年的住宿项目，重点关注来自西南弗吉尼亚州的低收入，代表性不足的青年，她刚刚完成了美国国际教育协会妇女倡议委员会主席的任期。该提案还详细介绍了她向女初高中学生伸出的援手，旨在让她们了解科学和工程领域的就业机会。该合作项目长期参与由NSF REU和IGERT奖支持的VT夏季本科生研究计划。可以预期将继续致力于这些和其他教育活动。

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.