Development of tunable DNA-based material technology

基于DNA的可调谐材料技术的开发

• 批准号: 10633159
• 负责人: Josephine Allen
• 金额: $ 22.88万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-06 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10633159
• 关键词: 3-Dimensional; Address; Agonist; Architecture; Behavior; Binding; Biochemistry; Biocompatible Materials; Biological; Biological Process; Biological Products; Biomedical Research; Cell Communication; Cell Culture System; Cell Culture Techniques; Cell model; Cell physiology; Cells; Chemicals; Chemistry; Collagen; Collagen Type I; Communities; Complex; Cultured Cells; DNA; DNA Library; Data; Development; Disease; Environment; Extracellular Matrix; Extracellular Matrix Proteins; Fiber; Fibrosis; Functional disorder; Future; Goals; Health; Human; Hydrogels; In Vitro; Inflammatory; Mechanics; Modeling; Names; Necrosis; Normal Cell; Pharmacology Study; Phenotype; Process; Property; Publishing; Reaction; Reproducibility; Research; Research Personnel; Research Project Grants; Shapes; Signal Transduction; Single-Stranded DNA; Site; System; Technology; Testing; Tissues; Translations; Work; aptamer; biomaterial compatibility; catalyst; cell behavior; cell growth; cell type; chemical conjugate; design; high reward; high risk; in vivo; innovation; insight; mechanical properties; pharmacologic; prototype; receptor; response; self assembly; stem cell differentiation; stem cells; technology development; three dimensional cell culture; validation studies

Project Summary/Abstract Within the biomedical field there is great effort to study a multitude of cell processes, including cell-cell communication, cell-matrix interactions, cell signaling, pharmacological effects, and differentiation to name a few. It is widely known that the more closely the cell culture system replicates the native cellular environment, the more closely the cultured cells will model their native behaviors. Knowing this, over the years, various forms of three-dimensional culture strategies have emerged as a superior advancement over 2D culture. The most promising approaches include those that mimic the native extracellular matrix, in its architecture, mechanics, and composition, thereby providing the ideal biological signaling and cellular recognition sites that promote normal cell behavior. Towards this goal, the focus of this technology development proposal is to develop a tunable, bioactive, DNA-based hydrogel platform that can meet these tissue specific requirements and serves to advance in vitro cell culture. This material technology is significant because the DNA-based hydrogel platform eliminates the need for complex chemical interactions and takes advantage of the rapid self-assembly and spontaneous fibril formation that occurs when DNA is complexed with ECM protein collagen. In addition, this platform utilizes functional DNA aptamers to render the hydrogel bioactive. This technology is poised to promote cellular functions that are more native and reproducible to a broad community of biomedical researchers. To achieve our goals, the aims of our project are 1) Examine to bulk material properties achievable with DNA- collagen based hydrogels; and 2) Functionalize DNA-hydrogels with bioactive DNA aptamers. Our studies will be compared to commonly used hydrogels and we will demonstrate biological impact through validation studies. Completion of the above-described aims is expected to reveal the full breadth and potential of DNA-collagen based materials to mimic tissue specific ECM and serve as a material platform for a broad array of biomedical studies. We intend to develop a library of DNA-collagen bulk matrix with well-defined synthesis conditions capable of tunable mechanical properties and bioactivity for a range of cell responses involved cell-cell interactions, cell-matrix interactions, pharmacological studies, modelled health or disease states of cells, mechanistic insight into varied cell phenotypes, stem cell studies, and an array of other fundamental studies of tissue specific cell behaviors.

项目总结/摘要 在生物医学领域内，存在大量的努力来研究大量的细胞过程，包括细胞-细胞（cell-cell 通信、细胞-基质相互作用、细胞信号传导、药理学作用和分化， 几个众所周知，细胞培养系统越接近地复制天然细胞环境， 培养的细胞将越接近地模拟它们的天然行为。知道这一点，多年来，各种形式的 三维文化战略的发展已经成为一个优于二维文化的上级进步。最 有希望的方法包括在其结构，力学， 和组合物，从而提供理想的生物信号传导和细胞识别位点， 正常的细胞行为。为了实现这一目标，本技术开发提案的重点是开发一种 可调的、生物活性的、基于DNA的水凝胶平台，其可以满足这些组织特异性要求， 促进体外细胞培养。这种材料技术意义重大，因为基于DNA的水凝胶平台 消除了复杂的化学相互作用的需要，并利用了快速的自组装， 当DNA与ECM蛋白胶原复合时发生的自发原纤维形成。另外这款 该平台利用功能性DNA适体使水凝胶具有生物活性。这项技术有望促进 这些细胞功能对于广泛的生物医学研究人员来说更天然和可再现。到 实现我们的目标，我们的项目的目的是1）检查散装材料的性质与DNA实现- 胶原基水凝胶;和2）用生物活性DNA适体官能化DNA水凝胶。我们的研究将 与常用的水凝胶进行比较，我们将通过验证研究证明生物影响。 上述目标的完成有望揭示DNA-胶原蛋白的全部广度和潜力 基于材料来模拟组织特异性ECM，并作为广泛的生物医学 问题研究我们打算建立一个具有明确合成条件的DNA-胶原蛋白基质库 对于涉及细胞-细胞的一系列细胞反应， 相互作用，细胞-基质相互作用，药理学研究，模拟细胞的健康或疾病状态， 对不同细胞表型的机械洞察，干细胞研究，以及一系列其他基础研究， 组织特异性细胞行为。