Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, RN115, Boston, MA, 02215, USA.
Department of Mechanical and Industrial Engineering, Northeastern University, 360 Huntington Avenue, 334 Snell Engineering Center, Boston, MA, 02115, USA.
BMC Musculoskelet Disord. 2019 Nov 25;20(1):562. doi: 10.1186/s12891-019-2854-z.
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 bone healing. However, the effects of initial healing phase, which includes the inflammatory stage, 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 quantified how faster MSC migration, stiffer granulation tissue, thicker callus, and smaller interfragmentary gap enhanced healing to some extent. However, 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 initial healing phase on healing outcome to better understand the biological and mechanobiological mechanisms and their utilization in the design and optimization of treatment strategies. It is also demonstrated through a simulation 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.
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机械和生物因素对骨愈合的作用。然而，在这些研究中，通常忽略了初始愈合阶段的影响，初始愈合阶段包括骨折后最初几天的炎症期、肉芽组织形成和初始骨痂形成。
在这项研究中，我们开发了一个基于有限元的模型，以模拟间充质干细胞（MSC）迁移、肉芽组织杨氏模量、骨痂厚度和骨断端间隙大小的不同扩散系数，以了解这些初始阶段参数对骨愈合的调节作用。
结果量化了 MSC 迁移更快、肉芽组织更硬、骨痂更厚、骨断端间隙更小在某种程度上如何促进愈合。然而，在达到一定阈值后，MSC 迁移率、肉芽组织刚度和骨痂厚度达到了饱和状态。因此，进行了参数研究以验证在初始阶段形成的骨痂在几何形状和材料特性方面具有理想的范围，以达到最有效的愈合时间。
本文的研究结果量化了初始愈合阶段对愈合结果的影响，以更好地理解生物学和力学生物学机制，并将其应用于治疗策略的设计和优化。通过模拟还表明，对于骨段接近的骨折，不需要骨痂形成。这一发现与原发性和继发性骨愈合的概念一致。
