A novel approach to study the cellular response to directional loading in relation to biomedical implants

人体中的许多组织都有一种结构，其组成部分有一定程度的排列。组织是以这种方式建造的，以使身体能够承受和施加姿势和运动所需的力量。一个典型的例子是肌腱的结构，它将肌肉连接到骨骼上。它们的主要结构成分是称为胶原蛋白的蛋白质纤维。这些胶原纤维具有分层排列的结构，因为这些纤维由一束束胶原纤维组成，每个胶原纤维由长分子链组成。因此，胶原蛋白具有宏观和微观的排列结构。当肌肉在运动过程中拉伸时，胶原蛋白纤维向力的方向排列，并承受载荷，允许肌肉移动骨骼。当组织受损时，会发生正常的修复过程，即细胞铺设胶原蛋白来重建结构，然而，修复后的组织的排列程度可能与原始组织不同，因此其承载能力将会降低。排列或各向异性的程度可以使用一种称为反射各向异性光谱(RAS)的技术来测量。RAS是一种非破坏性光学技术，它测量材料的各向异性程度或材料在界面上的相互作用。具有完全随机结构的材料将没有RAS光谱，但具有一定排列程度的材料将产生光谱，这将在微观和宏观水平上提供关于其结构的信息。此外，随着排列程度的变化，光谱也会发生变化，这给了我们一种灵敏的方法来评估材料的结构。RAS技术的主要优点是它可以在许多环境中分析不透明的材料，包括在水下，它还可以跟踪结构在发生时的排列变化。在这项研究中，我们将使用RAS来研究胶原蛋白作为一种简单分子在松弛和拉伸时附着在弹性材料上的排列程度。这将使我们能够研究胶原的微观结构，以及拉伸分子是否会增加其各向异性。我们还将使用RAS来分析细胞在松弛和拉伸时产生的胶原蛋白，这类似于组织修复过程。在这一部分，我们将研究胶原蛋白本身的拉伸，但也要检查拉伸细胞是否会刺激它们产生或多或少排列的胶原蛋白。这一点的重要性在于，如果拉伸细胞能刺激胶原蛋白更有效地排列，那么这可以用来改变损伤后正常的组织修复过程。最后，我们将使用RAS来研究从屠宰场收集的天然肌腱在松弛和拉伸时的胶原蛋白，并将这些光谱与以上描述的光谱进行比较。这将是RAS首次用于生物组织的研究。通过结合物理学家和生物材料科学家的专业知识，我们计划开发这种高度专业化的技术，为评估组织及其修复过程提供一种新的工具，这可能有助于设计医疗设备，以改善组织的愈合和修复。

Many tissues in the human body have a structure with a degree of alignment of the component parts. Tissues are built in this way to allow the body to withstand and exert forces required for posture and movement. A typical example of this is the structure of tendons which attach muscles to bone. Their principle structural components are protein fibres called collagen. These collagen fibres have a hierarchical aligned structure in that the fibres are made up of bundles of collagen fibrils and each collagen fibril is composed of long molecular chains. Thus collagen has a macroscopic and a microscopic aligned structure.When the muscles are stretched during movement the collagen fibres align to the direction of force and withstand the loading allowing the muscle to move the bone. When tissues are damaged a normal repair process occurs in which collagen is laid down by cells to rebuild the structure, however, the degree of alignment of the repaired tissue may not be the same as the original tissue and thus its ability to carry a load will be diminished.A material with an aligned structure is anisotropic. The degree of alignment or anisotropy can be measured using a technique called Reflection Anisotropy Spectroscopy (RAS). RAS is a non-destructive optical technique that measures the degree of anisotropy of a material or the interaction of materials at an interface. A material with a completely random structure will have no RAS spectrum but a spectrum would be produced from a material with a degree of alignment that will provide information on its structure at both the microscopic and macroscopic level. Furthermore as the degree of alignment changes the spectrum will change giving us a sensitive way to evaluate the structure of a material. Key advantages of the RAS technique are that it can analyse opaque materials in many environments including under water and it can also follow changes in the alignment of a structure as it is happening.In this study we will use RAS to study the degree of alignment of collagen as a simple molecule attached to an elastic material when it is relaxed and when it is stretched. This will allow us to investigate the microscopic structure of collagen and whether stretching the molecule increases its anisotropy. We will also use RAS to analyse collagen that has been produced by cells, similar to a tissue repair process, when it is relaxed and when it is stretched. In this part we will study the stretching of the collagen itself but also examine if stretching the cells stimulates them to produce more or less aligned collagen. The importance of this is that if stretching the cells stimulates collagen that is aligned more effectively then this can be used to change the normal tissue repair process following injury. Finally we will use RAS to study collagen in natural tendon, collected from an abattoir, when it is relaxed and when it is stretched and compare these spectra with those described above.This will be the first time RAS has been used to study biological tissue in this way. By combining the expertise of physicists and biomaterials scientists we plan to develop this highly specialised technique to provide a new tool for the evaluation of tissues and their repair processes that could help in the design of medical devices to improve tissue healing and repair.