Mechanical function of the primate craniofacial skeleton

该项目旨在建立计算机模型，使我们能够模拟和实验灵长类动物面部骨骼的生长，选择这些模型是因为它们在解剖学上与人类面部生长相似，因此提供了有关人类面部生长的信息。虽然遗传系统调节纳塔尔后颅面生长的早期部分，但后期发育受到机械负荷的强烈调节。颅面骨骼通过响应软组织（例如，大脑、舌头、肌肉）的扩张而在骨骼相遇处（缝合线）被动地生长来响应其直接的机械环境。它还通过建模和重塑机制来重新塑造，这些机制通过机械环境进行调制，从表面添加和移除骨骼。理解这些机械调节的过程是很重要的，因为它们不仅在正常生长中是必不可少的，而且在出现问题时也是如此。此外，我们还需要知道颅面形态的特征是如何在相关物种之间发生变化的。通常我们的牙齿不适合我们的嘴，但在历史上不是这样的;发生了什么？答案可能在于改变更软的饮食，改变不断增长的脸和随后的增长的机械负荷。更罕见的是，由于遗传因素，缝线可能过早融合或颅骨软骨可能无法充分生长。头骨的后续生长必须适应改变的起始条件并优化功能。机械信号是关键。了解机械调节应导致更好地预测正常和改变生长和面部骨骼的特征是遗传的，适应当地的力学理解。这对于解决有关化石和现存物种之间关系的争论很重要。了解面部生长的机械调节的一种方法是进行实验，其中动物被手术切割肌肉，移动牙齿，切除结构等，并观察结果。这是一项非常有利可图的研究，特别是在灵长类动物中，我们最近的亲戚，但现在在英国进行这项工作在道德和经济上都很困难。我们目前在这些领域的最佳信息来源来自欧洲以外的持续动物研究，特别是在美国。动物实验是非常有用的，但它们很难适当控制，而且进行和解释既冗长又耗时。如果我们有一个好的面部计算机模型，最终，头骨生长，它们可以被替换。虽然这样一个完整的模型是很长的路要走，我们计划在这个项目中模拟面骨适应的机械调节，这将允许预测的后果改变负荷。这项工作将建立在我们在过去三年中开发的计算机模型上，采用工程技术预测载荷如何分布（有限元分析/ FEA）。我们将把它们应用于两个相关的旧世界猴群，猕猴和白眉猴，它们在出生时有着相似的面孔，但成年后却有着截然不同的特征。因此，猕猴在上颌骨中形成了气窦，但白眉猴没有，相反，它们在面部的外部，上颌窝中形成了深的凹陷。我们将通过模拟我们所知道的骨如何适应来扩展我们的模型，以便使用初始载荷来驱动模拟的骨沉积或吸收。然后，我们将用我们的计算机模型进行一系列实验，以测试有关面部形状特征发展的想法，并在此过程中改进我们的模型和理解。通过这种方式，我们将推进面部如何生长的知识，并开发技术，这些技术将支持未来更完整的颅面发育模型，最终将支持对生物学，医学和人类和灵长类起源研究的适用性增长的预测。

This project aims to build computer models that allow us to emulate and experiment with growth of the facial skeleton in primates, chosen because they are anatomically similar to and therefore informative regarding human facial growth. Although genetic systems regulate the early part of post natal craniofacial growth, later development is strongly regulated by mechanical loading. The craniofacial skeleton responds to its immediate mechanical environment by passively growing where bones meet (the sutures) in response to the expansion of the soft tissues (e.g. brain, tongue, muscles). It is also resculpted by modelling and remodelling mechanisms that add and remove bone from surfaces, being modulated by the mechanical milieu. It is important we understand these mechanically regulated processes because they are essential not only in normal growth but also when things go wrong. Further we need to know how the features of craniofacial form that characterise and vary between related species come about. Commonly our teeth do not fit well to our mouths, yet in the historical past this was not the case; what has happened? The answer likely lies in the change to softer diets that alter the mechanical loading of the growing face and subsequent growth. More rarely sutures may fuse too early or skull cartilages may not grow adequately because of inherited conditions. The subsequent growth of the skull has to adapt to the altered starting conditions and optimise function. The mechanical signals are key in this. Understanding mechanical regulation should lead to better prediction of normal and altered growth and understanding of which features of the facial skeleton are inherited and which adapted to local mechanics. This is important in resolving arguments about the relationships among fossil and living species. One approach to understanding the mechanical regulation of the growth of the face is to carry out experiments in which animals are operated on to cut muscles, move teeth, excise structures etc and observe the outcomes. This has been a very profitable line of research especially in primates, our nearest relatives but now it is ethically and economically difficult to carry on this work in the UK. Our current best sources of information in these areas come from continuing animal studies outside Europe, especially in the USA. Animal experiments are very useful but they are difficult to properly control and lengthy and time consuming to carry out and interpret. They could be replaced if we had a good computer model of facial, and eventually, skull growth. While such a full model is long way off we plan in this project to emulate the mechanical regulation of facial bone adaptation that will allow prediction of the consequences of altered loading. The work will build on computer models that we have developed over the past three years employing engineering techniques for predicting how loads are distributed (finite elements analysis / FEA). We will apply them to two related old world monkey groups, macaques and mangabeys, with similar faces at birth that develop very different features of adult form. Thus macaques develop air sinuses in the maxilla but mangabeys do not, instead they develop deep excavations of the external aspect of the face, the maxillary fossae. We will extend our models by simulating what we know of how bone adapts so that initial loading is used to drive simulated bone deposition or resorption. We will then carry out a series of experiments with our computer models to test ideas about the development of features of facial form and in so doing work to improve our models and our understanding. In this way we will advance knowledge of how the face grows and develop technologies that will underpin future, more complete models of craniofacial development that will eventually underpin predictions of growth with applicability in biology, medicine and studies of human and primate origins.