Electrokinetic lithography: in situ microengineering of anisotropic 3D collagen matrices

动电光刻：各向异性 3D 胶原基质的原位微工程

• 批准号: 10452905
• 负责人: Vinay V Abhyankar
• 金额: $ 22.19万
• 依托单位: ROCHESTER INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10452905
• 关键词: 3-Dimensional; Address; Affect; Architecture; Biocompatible Materials; Biomedical Research; Biomimetics; Biopolymers; Cell Communication; Cells; Charge; Collagen; Collagen Fiber; Collagen Type I; Communication; Cues; Deposition; Development; Developmental Biology; Disease; Endothelial Cells; Engineering; Environment; Epithelial; Extracellular Matrix; Fiber; Future; Gel; Goals; Heterogeneity; Immune; In Situ; Laboratories; Letters; Malignant Neoplasms; Microfluidics; Mission; Morphogenesis; Motion; National Institute of General Medical Sciences; Outcome; Population; Predictive Value; Process; Program Development; Property; Proteins; Reporting; Research; Research Support; Resolution; Shapes; Speed; Stimulus; Surface; System; T-Lymphocyte; Techniques; Technology; Testing; Tissues; Traction; Work; Writing; base; biofabrication; bioprinting; cancer cell; cell motility; design; electric field; fluid flow; insight; lithography; magnetic field; mechanical signal; particle; prototype; real-time images; response; self assembly; success; technology development; technology research and development; tool; tumor microenvironment

Summary In this project we will develop a technology called electrokinetic lithography (EKL) that will fill a technology void in the current state-of-the-art 3D aligned collagen fiber microengineering techniques. To mimic the structurally heterogenous environment found in the native extracellular matrix (ECM), we will sequentially combine extensional fluid flows with electric field driven bead motion (electrokinetics) to “write” cellular-scale discontinuities between domains of aligned collagen fibers within biomimetic 3D collagen gel. Technology development will be carried out with the followings aims: 1) Establish flow-based collagen fiber alignment and characterize electrokinetic transport parameters, and 2) Develop a microfluidic platform to engineer discontinuities within aligned 3D gel environments and validate cell motility responses. The success of this project will establish a transferrable lab prototype and support unprecedented studies that explore how cells respond to local disruptions in the aligned fibrous microarchitecture. Our technique will support new lines of exploration related to motility, sensing, and cell-cell communication within structurally heterogeneous environments, and address research questions cannot be currently answered with state-of- the-art collagen alignment techniques. This project directly aligns with the NIGMS mission of developing tools that enable potentially transformative biomedical research.

概括 在这个项目中，我们将开发一种称为动电光刻 (EKL) 的技术，该技术将填补 当前最先进的 3D 排列胶原纤维微工程技术中存在空白。为了模仿 在天然细胞外基质（ECM）中发现结构异质环境，我们将依次 将拉伸流体流动与电场驱动的珠子运动（电动学）相结合以“写入”细胞规模 仿生 3D 胶原凝胶内排列的胶原纤维域之间的不连续性。技术 开发将实现以下目标：1）建立基于流动的胶原纤维排列和 表征动电传输参数，2) 开发微流体平台来设计 对齐的 3D 凝胶环境中的不连续性并验证细胞运动反应。 该项目的成功将建立一个可转移的实验室原型并支持前所未有的研究 探索细胞如何应对排列的纤维微结构的局部破坏。我们的技术将 支持结构内与运动、传感和细胞间通信相关的新探索 异构环境，并解决目前无法用状态来回答的研究问题 最先进的胶原蛋白排列技术。该项目与 NIGMS 开发工具的使命直接相关 从而实现潜在的变革性生物医学研究。