An engineering approach to assess effect of bleeding on bone for patients with bleeding disorders

该项目将结合多尺度的芯片和体外方法，用于治疗与血友病关节病（HJD）表现相似的骨病。总之，这些方法将回答机械调节的变化是否预测囊肿的出现，以及囊肿或血液本身是否是踝关节形态变化的主要原因；确定踝关节血液病发病的病因。具体方法的例子：了解由于HJD骨骼变化导致的关节生物力学变化：基于MRI和高分辨率CT图像的关节水平计算模型将根据体外数据进行验证。在体外，你将测量未患病供体踝关节的关节生物力学和压力，这些踝关节将被改变以产生类似HJD的缺陷。模拟血友病和其他血液疾病导致的骨骼机械调节变化：开发机械调节网络模型，以解释遗传变化和直接血液暴露对骨骼重塑和适应的影响。评估血液暴露对骨组织微机械环境和细胞的影响。您将在体外和计算机上开展基础工作，以分离特定分子或特定骨细胞的生物力学效应

This project will use a combination of multiscale in-silico and in-vitro approaches developed for bone diseases with similar presentations to Haemophilia Joint Disease (HJD). Together, these methods will answer whether changes in mechanoregulation predicts the appearance of cysts, and whether the cysts or the blood in itself are the main cause of morphological changes in the ankle; defining an aetiology of the onset of ankle haemarthropathy. Example of specific approaches: Understand changes in the joint biomechanics due to changes in bone for HJD: Joint level computational models based on MRI and high-resolution CT images will be validated against in-vitro data. In-vitro, you will measure joint biomechanics and pressure for non-diseased donor ankles which will be altered to create defects similar to HJD presentation. In-silico you will predict changes in internal pressure for patients with HJD Model changes in bone mechanoregulation due to Haemophilia and other blood disorders: you will develop mechanoregulation network models to account for genetic changes and direct blood exposure on bone remodelling and adaptation Assess the effect of blood exposure on bone tissue micro-mechanical environment and cells: you will develop in vitro and in silico fundamental work to isolate the biomechanical effect of specific molecules or for specific bone cells