反向动力化：不同剂量重组人骨形态发生蛋白-2下固定器刚度对大骨缺损愈合方式及效率的影响
Reverse Dynamization: Influence of Fixator Stiffness on the Mode and Efficiency of Large-Bone-Defect Healing at Different Doses of rhBMP-2.
作者信息
Glatt Vaida, Bartnikowski Nicole, Quirk Nicholas, Schuetz Michael, Evans Christopher
机构信息
Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology, Brisbane, Queensland, Australia
Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology, Brisbane, Queensland, Australia.
出版信息
J Bone Joint Surg Am. 2016 Apr 20;98(8):677-87. doi: 10.2106/JBJS.15.01027.
BACKGROUND
Reverse dynamization is a technology for enhancing the healing of osseous defects. With use of an external fixator, the axial stiffness across the defect is initially set low and subsequently increased. The purpose of the study described in this paper was to explore the efficacy of reverse dynamization under different conditions.
METHODS
Rat femoral defects were stabilized with external fixators that allowed the stiffness to be modulated on living animals. Recombinant human bone morphogenetic protein-2 (rhBMP-2) was implanted into the defects on a collagen sponge. Following a dose-response experiment, 5.5 μg of rhBMP-2 was placed into the defect under conditions of very low (25.4-N/mm), low (114-N/mm), medium (185-N/mm), or high (254-N/mm) stiffness. Reverse dynamization was evaluated with 2 different starting stiffnesses: low (114 N/mm) and very low (25.4 N/mm). In both cases, high stiffness (254 N/mm) was imposed after 2 weeks. Healing was assessed with radiographs, micro-computed tomography (μCT), histological analysis, and mechanical testing.
RESULTS
In the absence of dynamization, the medium-stiffness fixators provided the best healing. Reverse dynamization starting with very low stiffness was detrimental to healing. However, with low initial stiffness, reverse dynamization considerably improved healing with minimal residual cartilage, enhanced cortication, increased mechanical strength, and smaller callus. Histological analysis suggested that, in all cases, healing provoked by rhBMP-2 occurred by endochondral ossification.
CONCLUSIONS
These data confirm the potential utility of reverse dynamization as a way of improving bone healing but indicate that the stiffness parameters need to be selected carefully.
CLINICAL RELEVANCE
Reverse dynamization may reduce the amount of rhBMP-2 needed to induce healing of recalcitrant osseous lesions, reduce the time to union, and decrease the need for prolonged external fixation.
背景
反向动力化是一种促进骨缺损愈合的技术。使用外固定器时，最初将缺损处的轴向刚度设置得较低，随后再增加。本文所述研究的目的是探讨不同条件下反向动力化的疗效。
方法
用可在活体动物上调节刚度的外固定器固定大鼠股骨缺损。将重组人骨形态发生蛋白-2（rhBMP-2）植入胶原海绵上的缺损处。在进行剂量反应实验后，在极低（25.4 N/mm）、低（114 N/mm）、中（185 N/mm）或高（254 N/mm）刚度条件下，将5.5 μg rhBMP-2放入缺损处。用2种不同的起始刚度评估反向动力化：低（114 N/mm）和极低（25.4 N/mm）。在这两种情况下，2周后施加高刚度（254 N/mm）。通过X线片、微计算机断层扫描（μCT）、组织学分析和力学测试评估愈合情况。
结果
在没有动力化的情况下，中等刚度的固定器提供了最佳的愈合效果。从极低刚度开始的反向动力化对愈合有害。然而，初始刚度较低时，反向动力化可显著改善愈合，残余软骨最少，皮质化增强，机械强度增加，骨痂较小。组织学分析表明，在所有情况下，rhBMP-2引发的愈合均通过软骨内成骨发生。
结论
这些数据证实了反向动力化作为改善骨愈合方法的潜在效用，但表明刚度参数需要谨慎选择。
临床意义
反向动力化可能减少诱导顽固性骨病变愈合所需的rhBMP-2量，缩短愈合时间，并减少长期外固定的需求。
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