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

基于生物材料的策略有可能通过理解和控制细胞与环境的行为方式来改善人类健康，这将最终导致用于治疗疾病的材料的发展。细胞被一种动态的四维细胞外基质（ECM）所包围，该基质由大分子形式的化学和机械信号组成，这些信号随时间和空间的变化而变化。目前，我们依赖于过时和低效的工具来研究存在于ECM中的细胞-物质界面。因此，我们需要构建的材料，其属性可以很容易地定制和改变随着时间的推移，以探测在细胞-材料界面的相互作用。对于材料科学家和生物学家来说，这是一个很好的机会，可以共同努力，更好地理解细胞环境的重要性，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三维细胞培养中化学性质随时间变化的动态细胞-材料界面；以及高效快速地筛选存在于体内的大量细胞-物质相互作用的能力。先前的研究表明，在水凝胶中创建生物分子的三维模式来模拟自然环境是可能的。这些进展是实质性的，但仍然缺乏能力：(a)模拟环境的时间依赖性，(b)同时研究各种各样的条件。***未来5年我的研究计划的主要目标是：(1)开发化学性质在空间和时间上调整的水凝胶，以研究和控制细胞-材料界面，包括可逆细胞粘附的演示；(2)开发水凝胶系统，快速筛选不同化学环境对细胞活动的影响，包括癌细胞侵袭。***该计划将产生必要的工具来探测细胞-物质相互作用，并导致治疗性生物材料的发展。这项工作对于涉及干细胞和癌症的再生策略尤其重要，因为这两种细胞类型都受其环境的高度影响。这项研究将有助于巩固加拿大在生物材料研究方面的领导地位，并从长远来看，使生物材料促进人类健康。**

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 Currently, we rely on outdated and inefficient tools to study the cell-material interfaces that exists in the ECM.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. **