Novel systems for the application of isolated tensile, compressive, and shearing stimulation of distraction callus tissue

BackgroundDistraction osteogenesis is a procedure widely used for the correction of large bone defects. However, a high complication rate persists, likely due to insufficient stability during maturation. Numerical fracture healing models predict bone regeneration under different mechanical conditions allowing fixation stiffness optimization. However, most models apply a linear elastic material law inappropriate for the transient stresses/strains present during limb lengthening or segment transport. They are also often validated using in vivo osteotomy models lacking precise mechanical regulation due to the unavoidable stimulation of secondary interfragmentary motion during ambulation under finitely stiff fixation. Therefore, in order to create a robust numerical model of distraction osteogenesis, it is necessary to both characterize the new tissue’s viscoelasticity during distraction and determine the influence of strictly isolated stimulation in each loading mode (tension, compression, and shear) to account for potential differences in mechanical and histological response.AimTwo electromechanical fixators with integrated load cells were designed to precisely perform and monitor in vivo lateral distraction and isolated stimulation in sheep tibiae using a mobile, hydroxyapatite-coated titanium plate. The novel surgical procedure circumvents osteotomy, eliminating the undesirable and unquantifiable mechanical stimulation during ambulation.MethodsAfter a 10-day post-surgery latency period, two 0.275 mm distraction steps were performed daily for 10 days. The load cell collected data before, during, and after each distraction step and was terminated after no less than one minute from the time of distraction. A 7-day consolidation period separated the distraction phase and 18-day stimulation phase. Stimulation was carried out in isolated tension, compression, or shear while recording force/time data. Each stimulation session consisted of 120 cycles with a magnitude of either 0.1 mm or 0.6 mm in the tension and compression groups and 1.0 mm in the shear group. The animals were euthanized after a 3-day holding period following stimulation.ResultsOur initial results show that the tissue progressively stiffens and maintains an increasingly large residual traction. The force curves during compressive stimulation show a progressive drift from compression toward tension. We hypothesize that this behavior may be due to the preferential flow of fluid outward from the tissue and a greater resistance to reabsorption during the plate’s return to the starting position.

研究背景：牵张成骨（distraction osteogenesis）是目前临床用于修复大型骨缺损的常用术式，但术后并发症发生率仍居高不下，其核心诱因大概率为骨成熟阶段的固定稳定性不足。骨折愈合数值模型可预测不同力学条件下的骨再生过程，从而实现固定刚度的优化。然而，现有多数模型采用线弹性本构定律，并不适配肢体延长或节段运输过程中出现的瞬态应力与应变；同时，这类模型常基于体内截骨模型进行验证，但由于有限刚度固定（finitely stiff fixation）下行走活动不可避免地会引发骨断端间二次微动（secondary interfragmentary motion），此类模型难以实现精确的力学调控。因此，若要构建可靠的牵张成骨数值模型，需同时完成两项工作：一是表征牵张过程中新生组织的黏弹性（viscoelasticity），二是明确每种加载模式（loading mode）下单独刺激的影响，以覆盖力学与组织学响应中可能存在的差异。

研究目标：本研究设计了两款集成测力传感器（load cells）的机电式外固定架（electromechanical fixators），可借助可移动羟基磷灰石涂层钛板，精准完成绵羊胫骨的体内侧方牵张操作并同步监测，同时可对其实施单独刺激。该创新手术方案规避了截骨术，消除了行走活动中产生的不良且无法量化的力学刺激。

研究方法：术后10天潜伏期（post-surgery latency period）结束后，每日进行两次0.275 mm的牵张步骤（distraction steps），持续10天。测力传感器在每次牵张操作的前后及过程中采集数据，且于牵张完成后至少持续采集1分钟后终止采集。牵张阶段与刺激阶段之间设置7天的骨愈合巩固期（consolidation period），随后进入为期18天的刺激阶段。刺激过程分别采用孤立的拉伸、压缩或剪切加载模式，同步记录力-时间数据。每一轮刺激会话包含120个循环周期（cycles），其中拉伸组与压缩组的位移幅值（magnitude）为0.1 mm或0.6 mm，剪切组的位移幅值为1.0 mm。刺激结束后经过3天观察期（holding period），对所有实验动物实施安乐死。

研究结果：本研究的初步结果显示，新生组织的刚度逐渐升高，且残余牵张力持续增大。压缩刺激过程中的力-时间曲线呈现出从压缩向拉伸的渐进性偏移。我们推测该现象可能源于两个因素：一是组织内流体优先向外渗出，二是外固定架回归初始位置时，组织的重吸收（reabsorption）阻力更高。