DEVISE: Engineered viscoelasticity in regenerative microenvironments

DEVISE：再生微环境中的工程粘弹性

• 批准号: EP/X038599/1
• 负责人: Manuel Salmeron-Sanchez
• 金额: $ 274.23万
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FX038599%2F1
• 关键词: DEVISE; Engineered; viscoelasticity; regenerative; microenvironments

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.

组织是粘弹性材料，其机械性能随时间而变化，但这一重要性能尚未纳入再生生物材料的设计中。众所周知，生物材料的机械性能会影响基本的细胞过程，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）分化的机械特性的工作都使用纯弹性材料。细胞通过拉力和通过膜受体接收机械反馈来探测其环境。由于粘弹性材料对力的反应具有时间依赖性过程，因此我们假设粘弹性将在间充质干细胞的分化中发挥重要作用，从而在再生生物材料的设计中发挥重要作用。该项目将开发 (a) 具有受控特性的新粘弹性水凝胶系列，包括生化功能（概括体内细胞外基质的特性）、极端机械特性（即极低/高弹性和粘性特性）和机械梯度； (b) 布里渊显微镜追踪这些充满细胞的材料的局部粘弹性特性随时间的变化。我们将利用小鼠半径模型中的临界尺寸缺陷，使用粘弹性材料来促进体内骨再生，并且在推动该领域向前发展的重大尝试中，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。