MECHANICAL MODULATION OF GROWTH IN PHYSES

骨骼和生长软骨的进行性变形通常被认为是由‘Hueter-Volkmann定律’控制的，该定律指出，与正常值相比，增加机械压缩会减缓生长，而生长板的负荷会减少，从而加速生长。先前的研究已经证实，恒定的负荷叠加在生长板周围的活体负荷上将调节其生长速度。这种现象只对个别物种的少数个别骨骼进行了量化，而决定特定骨骼对负荷的反应作为其生理正常生长速度、生长板细胞的大小和活动的一般规则尚不清楚。许多与骨生长速率相关(并可能控制)的变量已经被确定。这项工作将提供对骨生长的力学调节的更多了解，并最终允许通过支撑、肌肉刺激和手术等技术进行机械治疗的量化设计。这项拟议的研究将量化长骨和椎骨在正常条件下以及在机械压缩和牵张情况下的软骨内生长速度。四种不同的物种将在生长的早期阶段进行研究，当骨骼生长较慢时，将接近骨骼成熟。在额外的实验中，将通过研究只有夜间和白天的植骨负荷的影响来研究‘部分时间’治疗的可行性。生长板的特征属性(尺寸、细胞数量和细胞活性的测量)将被记录下来，并在经历不同机械应力的生长板之间进行比较。将开发统计模型，以显示生长的机械调节如何变化与每个生长板的特征属性的关系。这些分析将在一定程度上受到生长板特性之间已知的生理关系的指导。这项工作的结果将是了解给定的骨赘应该如何对给定的应力做出反应，这将有助于了解骨骼畸形的进展并指导其治疗。

Progressive deformities in bones and growth cartilages are commonly thought to be controlled by the 'Hueter-Volkmann Law' which states that growth is retarded by increased mechanical compression, and accelerated by reduced loading of the growth plate in comparison with normal values. It has been confirmed by previous studies that a constant load, superimposed on the ambient in vivo loading of a growth plate will modulate its rate of growth. This phenomenon has only been quantified for a few individual bones of individual species, and the general rules which determine a particular bone's response to load as a function of its physiologically normal growth rate, dimensions and activity of the growth plate cells are unknown. Many of the variables which covary with (and probably govern) bone growth rates have been identified. This work will provide greater understanding of the mechanical regulation of bone growth and eventually permit quantitative design of mechanical treatment by techniques such as bracing, muscle stimulation and surgery. The proposed studies will quantity the rate of endochondral growth of long bones and vertebrae under normal conditions and with mechanical compression and distraction. Four different species will be studied at an early stage of growth and nearer to skeletal maturity when the bones are growing more slowly. In additional experiments the feasibility of 'part-time' treatment will be investigated by studying the effects of physis loading during night-time and day-time only. The characteristic properties of the growth plate (dimensions, numbers of cells and measures of cellular activity) will be documented and compared between growth plates which had experienced different applied mechanical stresses. Statistical models will be developed to show how the mechanical modulation of growth varies in relationship to characteristic properties of each growth plate. These analyses will be guided in part by known physiological relationships between properties of growth plates. The result of this work will be an understanding of how a given physis should be expected to respond to a given stress, and this will be helpful to understand the progression of skeletal deformities and to guide their treatment.