DEVISE: Engineered viscoelasticity in regenerative microenvironments

组织是粘弹性材料，其机械性能随时间而变化，但这一重要特性尚未纳入再生生物材料的设计中。已知生物材料的机械性质影响基本细胞过程，包括细胞迁移、细胞生长和细胞分化。然而，大多数了解基质对间充质干细胞（MSC）分化的机械性能的工作都是使用纯弹性材料。细胞通过拉力和通过膜受体接收机械反馈来探测它们的环境。由于粘弹性材料的响应与时间依赖性的过程中的力，我们假设粘弹性将发挥根本性的作用，在间充质干细胞的分化，因此在再生生物材料的设计。该项目将开发（a）一个新的粘弹性水凝胶家族，具有可控的特性，包括生物化学功能（概括体内细胞外基质的性质），极端的机械性能（即非常低/高的弹性和粘性）和机械梯度;和（B）布里渊显微镜以跟踪这些载有细胞的材料的局部粘弹性随时间的变化。我们将使用粘弹性材料来促进体内骨再生，使用我们在小鼠桡骨模型中的临界尺寸的缺损，并且在将该领域向前推进的主要尝试中，我们将进一步开发布里渊显微镜来监测体内再生微环境的粘弹性特性。

Tissues are viscoelastic materials whose mechanical properties evolve with time and yet this important property has not been incorporated in the design of regenerative biomaterials. Mechanical properties of biomaterials are known to influence fundamental cellular process, including cell migration, cell growth and cell differentiation. However, most of the work to understand the mechanical properties of substrates on mesenchymal stem cell (MSC) differentiation has made use of pure elastic materials. Cells probe their environment by pulling forces and receiving mechanical feedback through membrane receptors. Since viscoelastic materials respond with a time dependent process to force, we hypothesise that viscoelasticity will play a fundamental role in the differentiation of mesenchymal stem cells and hence in the design of regenerative biomaterials. This project will develop (a) a new family of viscoelastic hydrogels with controlled properties that include biochemical functionalities (recapitulating the properties of the extracellular matrix in vivo), extreme mechanical properties (i.e. very low/high elastic and viscous properties) and mechanical gradients; and (b) Brillouin microscopy to follow the evolution of the local viscoelastic properties of these cell-laden materials as a function of time. we will use viscoelastic materials to promote bone regeneration in vivo using our critical-sized defect in the mouse radius model and, in a major attempt to move the field forward, we will further develop Brillouin microscopy to monitor the viscoelastic properties of regenerative microenvironments in vivo.