CAREER: DYNAMIC LIVING HYDROGEL NETWORKS FOR SPATIO-TEMPORAL CONTROL OF CELL SIGNALING

职业：用于细胞信号传导时空控制的动态活水凝胶网络

• 批准号: 2034202
• 负责人: Ankur Singh
• 金额: $ 23.4万
• 依托单位: Georgia Tech Research Corporation
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-01 至 2022-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2034202&HistoricalAwards=false
• 关键词: CAREER; DYNAMIC; LIVING; HYDROGEL; NETWORKS

Technical AbstractBiomaterials-based three-dimensional hydrogels that better reflect the extracellular microenvironment of native tissues are important for tissue repair and regeneration as well as cell-matrix interaction studies. Importantly, the biochemical signals between cell and surrounding matrix are dynamic over multiple time (seconds-weeks) and length (nm-cm) scales, and are dependent on tissue stiffness. Therefore, materials engineered to modulate cell response must be similarly dynamic in their spatio-temporal presentation of bio-ligands and material stiffness. Although hydrogels that control spatial and temporal presentation of bio-ligands by use of external triggers have been realized, these hydrogels have not yet provided 3 key properties: a) spatial control of cell signaling, b) simultaneous temporal presentation of bio-adhesivity, and c) independent control of bio-adhesivity and material stiffness to parse individual contributions to cell modulation. This NSF CAREER award, funded by the Biomaterials program in the Division of Materials Research, will enable development of a new class of nanocomposite hydrogels with control over the above mentioned three key properties within a single hydrogel. This work will advance current understanding of the role of biomaterial properties in controlling human stem cell fate through user-directed spatio-temporal control of cell-matrix interactions. This work will make interactive inquiry based learning permeate the underprivileged middle and high schools by training teachers and students. This CAREER award will grow the infrastructure of US engineers, in particular those from underrepresented minorities, with strong disciplinary competence in biomaterials through pedagogy and cutting-edge research.Non-Technical AbstractBiomaterials-based 3D hydrogels that better reflect the niche of native tissues and capture critical aspects of the dynamic microenvironment are of increasing importance for culturing of mammalian cells, including stem cells, for a wide range of applications in biomedicine. The flow of information between cells and their surrounding niche is spatially and temporally dependent on biochemical signals and cell-cell interactions. Despite advancement in the field of biomaterials, independent role of spatio-temporal biochemical signaling and biophysical properties of materials cannot be effectively studied using a single hydrogel system. This NSF CAREER award will overcome the current bottlenecks in biomaterials research by enabling the development of a new class of hydrogel that dynamically communicates with cells to control their fates. The proposed research will benefit society by developing advanced bio-functional tissues for regenerative medicine. In particular we expect this work to generate dynamic biomaterials for better understanding of stem cells and their interactions with local surroundings that will help treatment of neurological disorders and enable regeneration of neural grafts for short and long nerve gaps. The outcomes of this research will catalyze potential avenues of investigation in multiple disciplines, including cell culture, tissue fabrication, blood vessel generation, drug delivery, tumor engineering, and implants. This work will make interactive inquiry based learning permeate the underprivileged middle and high schools by training teachers and students. This CAREER proposal will grow the infrastructure of US engineers, in particular undergraduate and graduate students including those from underrepresented minorities, with strong disciplinary competence in biomaterials through pedagogy and cutting-edge research.

技术摘要基于生物材料的三维水凝胶可以更好地反映天然组织的细胞外微环境，对于组织修复和再生以及细胞-基质相互作用研究具有重要意义。重要的是，细胞和周围基质之间的生化信号在多个时间（秒-周）和长度（纳米-厘米）范围内是动态的，并且取决于组织硬度。因此，设计用于调节细胞反应的材料在生物配体和材料刚度的时空呈现方面必须具有类似的动态性。尽管通过使用外部触发来控制生物配体的空间和时间呈现的水凝胶已经实现，但这些水凝胶尚未提供3个关键特性：a）细胞信号传导的空间控制，b）生物粘附性的同时时间呈现，和c) 独立控制生物粘附性和材料刚度，以解析个体对细胞调节的贡献。该 NSF 职业奖由材料研究部生物材料项目资助，将有助于开发新型纳米复合水凝胶，并在单个水凝胶中控制上述三个关键特性。这项工作将通过用户指导的细胞-基质相互作用的时空控制，促进目前对生物材料特性在控制人类干细胞命运中的作用的理解。这项工作将通过培训教师和学生，使基于互动探究的学习渗透到贫困初高中。该职业奖将发展美国工程师的基础设施，特别是那些来自代表性不足的少数族裔的工程师，通过教育学和前沿研究在生物材料方面拥有强大的学科能力。非技术摘要基于生物材料的 3D 水凝胶可以更好地反映天然组织的利基并捕获动态微环境的关键方面对于哺乳动物细胞（包括干细胞）的培养越来越重要，以实现生物医学的广泛应用。细胞与其周围生态位之间的信息流在空间和时间上取决于生化信号和细胞间相互作用。尽管生物材料领域取得了进步，但使用单一水凝胶系统无法有效地研究材料的时空生化信号和生物物理性质的独立作用。该 NSF 职业奖将通过开发新型水凝胶来克服当前生物材料研究的瓶颈，该水凝胶可与细胞动态通信以控制其命运。拟议的研究将通过开发用于再生医学的先进生物功能组织来造福社会。我们特别希望这项工作能够产生动态生物材料，以更好地了解干细胞及其与局部环境的相互作用，这将有助于治疗神经系统疾病，并使短神经间隙和长神经间隙的神经移植物再生。这项研究的成果将促进多个学科的潜在研究途径，包括细胞培养、组织制造、血管生成、药物输送、肿瘤工程和植入物。这项工作将通过培训教师和学生，使基于互动探究的学习渗透到贫困初高中。该职业提案将增强美国工程师的基础设施，特别是本科生和研究生，包括来自代表性不足的少数族裔的学生，通过教学和前沿研究在生物材料方面拥有强大的学科能力。