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: 1554275
• 负责人: Ankur Singh
• 金额: $ 50万
• 依托单位: Cornell University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-01 至 2020-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1554275&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.

基于生物材料的三维水凝胶能够更好地反映原生组织的细胞外微环境，对于组织修复和再生以及细胞-基质相互作用的研究具有重要意义。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）尺度上是动态的，并且依赖于组织刚度。因此，设计用于调节细胞反应的材料必须在生物配体和材料刚度的时空呈现中具有类似的动态。虽然已经实现了利用外部触发来控制生物配体空间和时间呈现的水凝胶，但这些水凝胶尚未提供3个关键特性：a)细胞信号的空间控制，b)生物粘附性的同时时间呈现，以及c)生物粘附性和材料刚度的独立控制，以解析个体对细胞调节的贡献。这项由材料研究部生物材料项目资助的美国国家科学基金会职业奖，将有助于开发一种新型纳米复合水凝胶，这种水凝胶可以控制上述三个关键特性。这项工作将通过用户导向的细胞-基质相互作用的时空控制，推进当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。这项工作将通过对教师和学生的培训，使互动式探究学习渗透到贫困的初高中。该职业奖将通过教学法和前沿研究，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民族的工程师。基于生物材料的3D水凝胶能够更好地反映原生组织的生态位，并捕捉动态微环境的关键方面，这对于包括干细胞在内的哺乳动物细胞的培养越来越重要，在生物医学中有着广泛的应用。细胞及其周围生态位之间的信息流在空间和时间上依赖于生化信号和细胞间相互作用。尽管生物材料领域取得了长足的进步，但单一的水凝胶体系无法有效地研究材料的时空生化信号和生物物理特性的独立作用。这项NSF职业奖将通过开发一种新型的水凝胶来克服目前生物材料研究的瓶颈，这种水凝胶可以动态地与细胞交流，从而控制细胞的命运。这项研究将为再生医学开发先进的生物功能组织，从而造福社会。我们特别希望这项工作能够产生动态的生物材料，以更好地理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，并使短神经和长神经间隙的神经移植物再生。这项研究的结果将催化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。这项工作将通过对教师和学生的培训，使互动式探究学习渗透到贫困的初高中。该职业计划将通过教学法和前沿研究，发展美国工程师的基础设施，特别是本科生和研究生，包括那些来自代表性不足的少数民族的学生。