Mechano-biology of bone regeneration

骨痂牵张是一种外科技术，广泛应用于骨科手术中，如骨延长或骨缺损修复。尽管在过去的几十年里，这种治疗方法已经得到了改进，但并发症的发生率仍然很高，主要是由于生物力学条件不合适，运动量太大和组织应变太大。为了优化骨再生，固定装置以及牵张方案必须进一步优化。一个先决条件是更好地理解机械信号对骨形成的影响(机械生物学)。为了使这些知识对患者有用，需要数值模拟模型来计算不同临床条件下固定稳定性对骨再生的影响。现有的数值模型的一个重要缺陷是，它们不是基于可靠的数据，而是基于对发育中的组织再生的材料性质、作用于骨再生部位的力学信号以及机械生物组织分化规律的假设，因此，本建议旨在通过优化力学生物组织分化规律来开发一种改进的骨痂牵张数值模型。为此，我们将使用我们团队先前开发的一种新的动物模型，通过防止生理性肌肉骨骼负荷下的重叠机械信号来研究完全拉伸、压缩和剪切应变下的骨愈合。此外，我们还将测量愈合过程中再生组织的机械性能。力学条件的精确控制将通过力学数据和组织学数据的相关性来改进机械生物组织分化规律。新的信息将在我们现有的外侧骨痂分散的数值模型中实施。该模型将使用活体测量的机械组织属性数据进行校准。然后进行参数研究。不同方向和大小的碎块间运动将被模拟和评估，以确定它们是否对骨愈合至关重要。这项研究的结果将是发展强大的骨折愈合和骨痂牵张模型的重要一步，以计算不同临床条件下固定稳定性对骨再生的影响。

Callus distraction is a surgical technique, which is widely used in orthopaedic surgery for e.g. bone lengthening or defect healing. Although this treatment has been improved in the last decades, there is still a high rate of complications mainly due to unsuitable biomechanical conditions with too much movement and too high tissue strain. To optimize bone regeneration, the fixation devices as well as the distraction protocols have to be further optimized. A prerequisite is the better understanding of the effects of mechanical signals on bone formation (mechano-biology). To make this knowledge useful for the patients, numerical simulation models are needed to calculate the effect of the fixation stability on bone regeneration under different clinical conditions. An important limitation of existing numerical models is, that they are not based upon reliable data but upon assumptions in terms of the material properties of the developing tissue regenerate, the mechanical signals acting at the site of bone regeneration and the mechano-biological tissue differentiation rules.Therefore, this proposal aims to develop an improved numerical model for callus distraction by the optimization of the mechano-biological tissue differentiation rules. For this we will study bone healing under exclusive tensile, compression and shear strain by preventing overlapping mechanical signals from physiological musculoskelettal loading using a new animal model previously developed by our group. Furthermore, we will measure the mechanical properties of the tissue regenerate during the healing process. The exact control of the mechanical conditions will allow improvement of the mechano-biological tissue differentiation rules by the correlation of the mechanical and histological data. The new information will be implemented in our existing numerical model for lateral callus distraction. The model will be calibrated using the data of the mechanical tissue properties measured in vivo. Then a parametric study will be performed. Interfragmentary movements, which differ in direction and magnitude, will be simulated and evaluated as to whether they are critical or not for bone healing. The outcome of this study will be an important step forward in the development of powerful numerical fracture healing and callus distraction models to calculate the effect of the fixation stability on bone regeneration under different clinical conditions.