Development of tunable DNA-based material technology

基于DNA的可调谐材料技术的开发

• 批准号: 10430768
• 负责人: Josephine Allen
• 金额: $ 19.06万
• 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 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10430768
• 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; Custom; DNA; DNA Library; Data; Development; Disease; Environment; Extracellular Matrix; Extracellular Matrix Proteins; Fiber; Fibrosis; Functional disorder; Future; Goals; Gold; Health; Human; Hydrogels; In Vitro; Inflammatory; Mechanics; Modeling; Names; Necrosis; Normal Cell; Pharmacology; Pharmacology Study; Phenotype; Process; Property; Publishing; Reaction; Reproducibility; Research; Research Personnel; Research Project Grants; Shapes; Signal Transduction; Site; Study models; System; Technology; Testing; Tissues; Translations; Work; aptamer; base; biomaterial compatibility; catalyst; cell behavior; cell growth; cell type; design; high reward; high risk; in vivo; innovation; insight; mechanical properties; 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.

项目概要/摘要 在生物医学领域，人们付出了巨大的努力来研究多种细胞过程，包括细胞间的相互作用 通讯、细胞-基质相互作用、细胞信号传导、药理作用和分化等等 很少。众所周知，细胞培养系统越接近地复制天然细胞环境， 培养的细胞越能模拟其天然行为。知道这一点，多年来，各种形式 三维文化策略已经成为比二维文化更优越的进步。最 有前途的方法包括那些模仿天然细胞外基质的结构、力学、 和组成，从而提供理想的生物信号和细胞识别位点，促进 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 可调节、生物活性、基于 DNA 的水凝胶平台，可以满足这些组织的特定要求，并用于 推进体外细胞培养。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，并利用了快速自组装和 当 DNA 与 ECM 蛋白胶原复合时，会发生自发原纤维形成。此外，这 平台利用功能性DNA适体使水凝胶具有生物活性。这项技术有望推动 对于广大生物医学研究人员来说，细胞功能更加天然且可重复。到 为了实现我们的目标，我们项目的目标是 1) 检查 DNA 可实现的散装材料特性- 基于胶原蛋白的水凝胶； 2) 用生物活性 DNA 适体功能化 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其生物学影响。 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材料平台 研究。我们打算开发一个具有明确合成条件的 DNA-胶原蛋白基质库 能够针对涉及细胞间的一系列细胞反应调节机械性能和生物活性 相互作用、细胞-基质相互作用、药理学研究、细胞健康或疾病状态模型、 对各种细胞表型、干细胞研究以及一系列其他基础研究的机制洞察 组织特异性细胞行为。