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骨重建单元活动与机械应力、比表面积和抑制理论的相互作用决定了骨量的分布:来自 3D 计算模型的预测。

The interplay between BMU activity linked to mechanical stress, specific surface and inhibitory theory dictate bone mass distribution: Predictions from a 3D computational model.

机构信息

Facultad de Ingeniería, Universidad Nacional de Entre Ríos (UNER), Ruta 11, Km 10, Oro Verde, Entre Ríos, Argentina.

Instituto de Bioingeniería y Bioinformática, UNER, Consejo Nacional de Investigaciones Científicas y Técnicas, Ruta 11, Km 10, Oro Verde, Entre Ríos, Argentina.

出版信息

Comput Biol Med. 2022 Sep;148:105898. doi: 10.1016/j.compbiomed.2022.105898. Epub 2022 Jul 30.

Abstract

Bone mechanical and biological properties are closely linked to its internal tissue composition and mass distribution, which are in turn governed by the purposeful action of the basic multicellular units (BMUs). The orchestrated action of osteoclasts and osteoblasts, the resorbing and forming tissue cells respectively, in BMUs is responsible for tissue maintenance, repair and adaptation to changing load demands through the phenomenon known as remodelling. In this work, a computational mechano-biological model of bone remodelling based on the inhibitory theory and a new scheme of bone resorption introduced previously in a 2D model, is extended to a 3D model of the real external geometry of a femur under normal walking loads. Starting from a uniform apparent density (ratio of tissue local mass to total local volume) distribution, the BMU action can be shown to lead naturally to an internal density distribution similar to that of a real bone, provided that the initial density value is high enough to avoid unrealistic final mass deposition in zones of high energy density and excessive damage. Physiological internal density values are reached throughout the whole 3D geometry, and at the same time a 'boomerang'-like relationship between apparent and material density (ratio of tissue mass to tissue volume) emerges naturally under the proposed remodelling scheme. It is also shown here that bone-specific surface is a key parameter that determines the intensity of BMU action linked to the mechanical and biological requirements. Finally, by engaging in simulations of bone in disuse, we were able to confirm the appropriate selection of the model parameters. As an example, our results show good agreement with experimental measurements of bone mass on astronauts a fact that strengthens our belief in the insightful nature of our novel 3D computational model.

摘要

骨骼的机械和生物特性与其内部组织成分和质量分布密切相关,而后者又受到基本多细胞单位 (BMU) 的有目的活动的控制。在 BMU 中,破骨细胞和造骨细胞的协同作用——分别是吸收和形成组织的细胞——负责通过重塑现象来维持组织、修复和适应不断变化的负荷需求。在这项工作中,基于抑制理论和之前在二维模型中引入的新骨吸收方案,对基于骨重建的计算力学-生物学模型进行了扩展,以适应正常行走负荷下股骨真实外部几何形状的三维模型。从均匀的表观密度(组织局部质量与总局部体积的比值)分布开始,BMU 的作用可以自然地导致类似于真实骨骼的内部密度分布,前提是初始密度值足够高,以避免在高能量密度和过度损伤区域出现不切实际的最终质量沉积。整个 3D 几何形状都达到了生理内部密度值,同时,在所提出的重建方案下,表观密度和材料密度(组织质量与组织体积的比值)之间自然出现了“回旋镖”关系。在这里还表明,骨特异性表面积是决定与机械和生物学要求相关的 BMU 作用强度的关键参数。最后,通过对废用性骨的模拟,我们能够确认模型参数的适当选择。例如,我们的结果与宇航员骨量的实验测量结果非常吻合——这一事实增强了我们对我们新颖的 3D 计算模型的有见地性质的信心。

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