What's MEW in the UK? Engineering basement membranes using state-of-the-art biofabrication technologies

英国的MEW是什么？

• 批准号: EP/Y001656/1
• 负责人: Lucy Bosworth
• 金额: $ 20.97万
• 依托单位: University of Liverpool
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FY001656%2F1
• 关键词: What; MEW; UK; Engineering; basement

Tissue engineering commonly uses scaffolds that aim to mimic the structure of biological tissues; however, the scale and geometry of current approaches are dissimilar to those found in nature and these differences hamper the scaffolds' ability to support and control cell behaviour. A recent technological innovation however has led to a demonstrable advancement in producing scaffolds that possess appropriate scale and tailorable geometrical features. This state-of-the-art technology is called melt electro-writing (MEW); a high-resolution version of 3D printing where the material is produced from synthetic polymers, the fibre is laid down in defined orientations and geometries and, most importantly, where this fibre is much closer in size to the native extracellular matrix. MEW was invented by my International Collaborator - Prof. Paul Dalton (University of Oregon), and this project focuses on establishing MEW in the UK to allow superior tissue-mimic structures to be created that will then allow us to better study the structural effects of these scaffolds on cell and tissue behaviour. More specifically, this grant focuses on the growth and assembly of specialised tissues known as basement membranes.Basement membranes are an essential tissue present throughout the body. They provide the interaction point between sheets of cells and the underlying extracellular matrix. Here they act as signalling hubs controlling a wide variety of cellular responses including determining the specific cell types that the cells will become, and protecting these cells from the mechanical forces that move through the extracellular matrix. How basement membranes achieve this is through localised and specific differences in their make-up (i.e. composition) and by differences in the way those proteins are assembled (i.e. structure). Whilst the compositional aspects have been widely studied over many years, the structural aspects have only recently come to the fore.Our overarching hypothesis is that the structure of the extracellular matrix in terms of its topography and geometry, stiffness and pore size will each contribute to how basement membranes assemble on top of that matrix. Those differences in basement membrane assembly will then translate into changes in cell behaviour. In this project we will test this hypothesis by determining how the underlying extracellular matrix influences the way that basement membranes assemble and function. This is a large and fundamental question which is central to many aspects of mammalian biology and with potential therapeutic implications for degenerative and age-related health conditions. Robustly testing this hypothesis has historically been hampered by difficulties in producing accurate experimental models where the specific aspects of the extracellular matrix could be independently modified and their contribution evaluated. However, combining MEW with our existing scaffold fabrication technologies, which represents a step-change advancement in substrate production, means we are now able to precisely tailor the characteristics of the scaffolds and then analyse the cellular and basement membrane responses to these scaffolds.Our project therefore has one distinct aim: to create synthetic structures using scaffold fabrication technologies that mimic the physical properties of extracellular matrix topography, geometry and mechanics, and which go on to influence basement membrane assembly and cell behaviour.

组织工程通常使用旨在模拟生物组织结构的支架;然而，当前方法的规模和几何形状与自然界中发现的那些不同，这些差异阻碍了支架支持和控制细胞行为的能力。然而，最近的技术创新导致了生产具有适当规模和可定制几何特征的支架的明显进步。这种最先进的技术被称为熔融电写入（MEW）; 3D打印的高分辨率版本，其中材料由合成聚合物制成，纤维以定义的方向和几何形状铺设，最重要的是，这种纤维的尺寸更接近天然细胞外基质。MEW是由我的国际合作者Paul道尔顿教授（俄勒冈州大学）发明的，该项目的重点是在英国建立MEW，以创建上级组织模拟结构，从而使我们能够更好地研究这些支架对细胞和组织行为的结构效应。更具体地说，该基金主要关注被称为基底膜的特殊组织的生长和组装。基底膜是存在于整个身体的重要组织。它们提供了细胞片层和下层细胞外基质之间的相互作用点。在这里，它们作为信号中枢控制各种各样的细胞反应，包括确定细胞将成为的特定细胞类型，并保护这些细胞免受通过细胞外基质移动的机械力的影响。基底膜如何实现这一点是通过其组成（即组成）的局部和特定差异以及这些蛋白质组装方式（即结构）的差异。虽然组成方面已经被广泛研究了多年，结构方面最近才脱颖而出，我们的总体假设是，在其地形和几何形状，刚度和孔径的胞外基质的结构将各自有助于基底膜如何组装在该矩阵的顶部。这些基膜组装的差异将转化为细胞行为的变化。在这个项目中，我们将通过确定潜在的细胞外基质如何影响基底膜的组装和功能来验证这一假设。这是一个大的和基本的问题，这是核心的哺乳动物生物学的许多方面，并具有潜在的治疗意义的退行性和年龄相关的健康状况。历史上，由于难以产生准确的实验模型，难以对细胞外基质的特定方面进行独立修饰并评估其贡献，因此难以对这一假设进行有力的检验。然而，将MEW与我们现有的支架制造技术相结合，这代表了基质生产的一个飞跃性进步，意味着我们现在能够精确地定制支架的特性，然后分析细胞和基底膜对这些支架的反应。因此，我们的项目有一个独特的目标：使用模拟细胞外基质形貌、几何形状和力学的物理性质的支架制造技术来创建合成结构，并进而影响基底膜组装和细胞行为。