炎症反应和颗粒化Tissue特性对人骨折愈合影响的计算机模拟
Computational Modeling of the Effects of Inflammatory Response and Granulation Tissue Properties on Human Bone Fracture Healing
摘要：
骨愈合过程包括四个阶段：炎症反应、软骨痂形成、硬骨痂发育和重塑。力学生物学模型已被用于研究各种力学和生物因子〈动〉<动>在骨愈合中的作用。然而，愈合的初始阶段，包括骨折后最初几天内的炎症反应、肉芽组织形成和最初的骨痂形成，在这些研究中通常被忽略。在这项研究中，我们开发了一个基于有限元的模型来模拟不同水平的扩散系数的间充质干细胞（MSC）迁移，肉芽组织的杨氏模量，愈伤组织厚度和interfragmental间隙大小，以了解这些初始阶段参数对骨愈合的调节作用。结果表明，MSC迁移速度快、肉芽组织硬、骨痂厚和骨折间隙小在一定程度上促进愈合。在一定阈值后，MSC迁移率、肉芽组织硬度和骨痂厚度达到饱和状态。因此，进行了参数研究，以验证在初始阶段形成的愈伤组织（与实验观察结果一致）具有理想的几何形状和材料特性范围，以获得最有效的愈合时间。本文的研究结果量化了愈合初始阶段对愈合结果的影响，以更好地了解生物学和机械生物学机制及其在治疗策略设计和优化中的应用。模拟结果还表明，对于骨折，其中骨段非常接近，不需要骨痂发育。这一发现与原发性和继发性骨愈合的概念一致。
英文摘要：
Bone healing process includes four phases: inflammatory response, soft callus formation, hard callus development, and remodeling. Mechanobiological models have been used to investigate the role of various mechanical and biological factors on the bone healing. However, the initial phase of healing, which includes the inflammatory response, the granulation tissue formation and the initial callus formation during the first few days post-fracture, are generally neglected in such studies. In this study, we developed a finite-element-based model to simulate different levels of diffusion coefficient for mesenchymal stem cell (MSC) migration, Young's modulus of granulation tissue, callus thickness and interfragmentary gap size to understand the modulatory effects of these initial phase parameters on bone healing. The results showed that faster MSC migration, stiffer granulation tissue, thicker callus and smaller interfragmentary gap enhanced healing to some extent. After a certain threshold, a state of saturation was reached for MSC migration rate, granulation tissue stiffness and callus thickness. Therefore, a parametric study was performed to verify that the callus formed at the initial phase, in agreement with experimental observations, has an ideal range of geometry and material properties to have the most efficient healing time. Findings from this paper quantified the effects of the healing initial phase on healing outcome to better understand the biological and mechanobiological mechanisms and their utilization in the design and optimization of treatment strategies. Simulation outcomes also demonstrated that for fractures, where bone segments are in close proximity, callus development is not required. This finding is consistent with the concepts of primary and secondary bone healing.
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