Novel Assessment of the Osteoarthritic Hip Subchondral Bone: a Combined Experimental and Computational Investigation

骨关节炎（OA）是一种影响人体关节的常见疾病，它会随着时间的推移而退化。虽然OA被认为是一种主要与软骨有关的疾病，但实际上已经观察到软骨下骨的主要变化。事实上，我们还不知道退行性变是从骨头还是软骨开始的。病变的髋关节真的很痛，可以通过全髋关节置换术来修复，这是一种成功但有侵入性的手术，在手术过程中，部分股骨和骨盆被假体取代。如果我们想要开发侵入性较小的治疗方法（例如药物治疗或可注射的生物材料），那么更好地了解OA对关节组织的影响是至关重要的。特别是，我们需要了解病理组织在载荷下是如何变形的。然而，这些材料（骨和软骨）的复杂性使得测量它们的形态特性和力学响应之间的关系非常难以测量。该项目的目标是使用最先进的实验，成像和计算技术来测量骨关节炎髋关节股骨头的软骨下骨在载荷下如何变形，强调骨微结构与其失效行为之间的可能关系。由于近年来基于高分辨率图像的数字图像相关技术的发展，无法通过实验测量骨样品在载荷作用下的三维变形。此外，为了估计相同骨骼在不同载荷条件下的破坏行为，我们需要稳健和准确的计算模型，例如应用于高分辨率图像的微有限元方法。在这个项目中，我们将采用过去几年在我的小组中开发的方法来研究OA中软骨下骨的变形。我们将使用最近获得的微型计算机断层扫描（microCT）系统以高分辨率扫描骨骼，一个定制的机械测试设备，适合于微型ct进行压缩，直到股骨头失效，以及一个数字体积相关（DVC）算法，可以测量骨骼的三维变形。我们还将生成最先进的计算模型，这些模型可以通过DVC测量来验证，然后可以用来估计相同骨骼在不同载荷情况下的变形。在我的小组中，我们已经使用了类似的方法，成功地验证了计算模型对部分小梁骨的预测。在这个项目中，我们将采用这个程序来分析整个股骨头的行为。通过结合获得的数据，我们将能够了解骨关节炎如何影响股骨头软骨下骨的形态测量学、密度测量学和力学特性。这些信息将有助于开发新的植入物和/或药物干预治疗髋关节骨关节炎。类似的方法可以扩展到受OA影响的其他关节。

Osteoarthritis (OA) is a common disease that affects human joints, which degenerate over time. While OA is considered a disease mainly related to the cartilage, in fact major changes of the subchondral bone have been observed. In fact, we do not know yet if the degeneration starts from the bone or from the cartilage. Pathologic hip joints are really painful and can be fixed with a total hip replacement, a successful but invasive surgery during which parts of the femur and of the pelvis are replaced with prostheses. If we want to develop less invasive treatments (e.g. drug treatments or injectable biomaterials) it is fundamental to better understand the effect of OA to the joint tissues. In particular, we need to understand how the pathologic tissue deforms under loading. However, the complexity of such materials (bone and cartilage) makes the measurement of the relationship between their morphological properties and their mechanical response very hard to measure. The goal of this project is to use state of the art experimental, imaging and computational techniques to measure how the subchondral bone of the femoral head of osteoarthritic hips deforms under loading, underlining possible relationships between the bone microarchitecture and its failure behaviour. Since the recent development of digital image correlation techniques based on high-resolution images, there was no way to measure experimentally the 3D deformation of bone samples under load. Moreover, in order to estimate the failure behaviour of the same bone under different loading conditions, we need robust and accurate computational models, such as the micro finite element approach, applied to high-resolution images. During this project we will adapt the methodologies developed over the past years in my group to study the deformation of the subchondral bone in OA. We will use a recently acquired micro computed tomography (microCT) system for scanning the bones at high resolution, a custom made mechanical testing device that fits within the microCT for performing compress until failure the femoral heads, and a digital volume correlation (DVC) algorithm that can measure the three dimensional deformation of the bones. We will also generate state of the art computational models that can be validated with the DVC measurements and can be then used to estimate the deformation of the same bones under different loading scenarios. We already used a similar approach in my group to successfully validate the predictions of computational models for portions of trabecular bone. In this project we will adapt this procedure for analysing the behaviour of whole femoral head. By combining the obtained data we will be able to understand how osteoarthritis affects the morphometric, densitometric and mechanical properties of the subchondral bone of the femoral head. This information will help in the development of new implants and/or pharmacological interventions to treat osteoarthritic hip. Similar approaches can then be extended for other joints affected by OA.