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.

项目摘要/摘要 在生物医学领域内，有巨大的努力来研究多种细胞过程，包括细胞细胞 通信，细胞 - 矩阵相互作用，细胞信号传导，药理学效应以及命名的分化 很少。众所周知，细胞培养系统的复制越接近，天然细胞环境， 培养的细胞越接近地模拟其本地行为。多年来知道这一点，各种形式 三维文化策略的出现是超过2D文化的卓越进步。最多 有前途的方法包括那些模仿本地细胞外基质的方法，其结构，力学， 和组成，从而提供促进的理想生物信号传导和细胞识别位点 正常的细胞行为。朝向这个目标，该技术发展建议的重点是开发一个 可调，生物活性，基于DNA的水凝胶平台，可以满足这些组织特定的要求并用于 推进体外细胞培养。这种材料技术很重要，因为基于DNA的水凝胶平台 消除了复杂化学相互作用的需求，并利用快速的自组装和 当DNA与ECM蛋白胶原蛋白复合时，会自发的原纤维形成。此外，这 平台利用功能性DNA适体呈现水凝胶生物活性。这项技术有望促进 广泛的生物医学研究人员社区更具本性和可再现的细胞功能。到 实现我们的目标，我们项目的目标是1）检查以DNA-可实现的批量材料特性 基于胶原蛋白的水凝胶； 2）用生物活性DNA适体功能功能化DNA-Hydrecels。我们的研究将 将其与常用水凝胶进行比较，我们将通过验证研究来证明生物学影响。 上述目标的完成有望揭示DNA-胶原蛋白的全部宽度和潜力 基于模拟组织特异性ECM的材料，并用作广泛生物医学阵列的材料平台 研究。我们打算开发一个具有明确定义的合成条件的DNA-胶原块矩阵库 能够对一系列细胞反应进行可调的机械性能和生物活性，涉及细胞细胞 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， 对各种细胞表型，干细胞研究以及一系列其他基本研究的机械洞察力 组织特异性细胞行为。