Dynamic biomaterials to study, manipulate and screen cell-matrix interactions

用于研究、操纵和筛选细胞-基质相互作用的动态生物材料

• 批准号: RGPIN-2015-05429
• 负责人: Wylie, Ryan
• 金额: $ 1.82万
• 依托单位: McMaster University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=680606
• 关键词: Dynamic; biomaterials; study; manipulate; screen

Biomaterials based strategies have the potential to improve human health by understanding and controlling the way cells behave with their environment, which will ultimately lead to the development of materials for the treatment of diseases. Cells are surround by a dynamic four-dimensional extracellular matrix (ECM) composed of chemical and mechanical signals in the form of macromolecules that change in space and time. Currently, we rely on outdated and inefficient tools to study the cell-material interfaces that exists in the ECM. Therefore, we need to build materials where properties can be easily tailored and changed over time to probe interactions at the cell-material interface. There is a great opportunity for material scientists and biologists to work together to better understand the importance of the cellular environment and better elucidate how, when and why materials influence cellular behaviours.*** Currently, we lack the tools necessary to study and mimic the dynamic cell-material interface in 3D cell cultures where chemical properties vary over time; and the ability to efficiently and rapidly screen the numerous cell-material interactions that exist in vivo. Previous work has shown it is possible to create three-dimensional patterns of biomolecules within hydrogels to mimic the natural environment. These advances were substantial but still lack the ability to: (a) mimic the time-dependent nature of the environment, (b) simultaneously study a large variety of conditions.*** Key objectives of my research program during the next 5 years are: (1) develop hydrogels where chemical properties are tuned in space and time to study and control the cell-material interface, including the demonstration of reversible cell adhesion; and (2) develop hydrogel systems to rapidly screen the effects of different chemical environments on cellular activities, including cancer cell invasion. *** This program will yield the tools necessary to probe cell-material interactions, and lead to the development of therapeutic biomaterials. This work is particularly important for regenerative strategies involving stem cells and cancer, since both these cell types are highly influenced by their environment. This research will help solidify Canada as a leader in biomaterials research and, in the long-term, lead to biomaterials to advance human health. **

基于生物材料的策略有潜力通过理解和控制细胞与其环境的行为方式来改善人类健康，这最终将导致用于治疗疾病的材料的开发。细胞被动态的四维细胞外基质（ECM）包围，该基质由随空间和时间变化的大分子形式的化学和机械信号组成。目前，我们依靠过时且低效的工具来研究 ECM 中存在的细胞-材料界面。因此，我们需要构建可以轻松定制属性并随时间改变的材料，以探测细胞-材料界面的相互作用。材料科学家和生物学家有很好的机会共同努力，更好地了解细胞环境的重要性，并更好地阐明材料如何、何时以及为何影响细胞行为。*** 目前，我们缺乏必要的工具来研究和模拟 3D 细胞培养物中的动态细胞材料界面，其中化学性质随时间变化；以及有效快速筛选体内存在的众多细胞-材料相互作用的能力。先前的工作表明，可以在水凝胶内创建生物分子的三维图案来模拟自然环境。这些进步是巨大的，但仍然缺乏以下能力：(a) 模拟环境的时间依赖性，(b) 同时研究多种条件。*** 我的研究计划在未来 5 年的主要目标是：(1) 开发水凝胶，其化学性质在空间和时间上进行调整，以研究和控制细胞-材料界面，包括演示可逆的细胞粘附； （2）开发水凝胶系统来快速筛选不同化学环境对细胞活动（包括癌细胞侵袭）的影响。 *** 该计划将产生探测细胞-材料相互作用所需的工具，并促进治疗性生物材料的开发。这项工作对于涉及干细胞和癌症的再生策略特别重要，因为这两种细胞类型都受到其环境的高度影响。这项研究将有助于巩固加拿大在生物材料研究领域的领先地位，并从长远来看，推动生物材料促进人类健康。 **