Combined use of low-intensity pulsed ultrasound and rhBMP-2 to enhance bone formation in a rat model of critical size defect.
Combined use of low-intensity pulsed ultrasound and rhBMP-2 to enhance bone formation in a rat model of critical size defect.
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DOI：
10.1097/bot.0000000000000067
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发表时间：
2014-10
影响因子：
2.3
通讯作者：
Virdi AS
中科院分区：
文献类型：
--
作者：
Angle SR;Sena K;Sumner DR;Virkus WW;Virdi AS
骨修复受生物因素和局部力学环境的调节。我们假设，低强度脉冲超声（LIPUS）和重组人骨形态发生蛋白-2（rhBMP-2）的联合使用将协同或相加地增强骨再生模型模拟骨科创伤学中更困难的情况。用含rhBMP-2（0、1.2、6或12μg; n=30）的可吸收胶原海绵替代大鼠股骨缺损。每组平均分为每天接受LIPUS或假刺激治疗。在4周时，使用定量（X射线照相术和显微计算机断层扫描）、定性（组织学）和功能（生物力学）终点评估新骨形成。早在2周时，与假手术对照组相比，含1.2μg rhBMP-2的LIPUS显著改善了放射学愈合。定量地，使用具有6μg rhBMP-2的LIPUS显著增加骨体积。然而，使用12μg rhBMP-2的LIPUS表明骨痂尺寸减小，而不影响骨体积，这在组织学上也可观察到，显示原始缺损区域中的组织化板层骨和重新填充的骨髓。在组织学上，单独1.2μg rhBMP-2显示缺损中存在未钙化的软骨，其通过LIPUS治疗而减少。在生物力学方面，LIPUS治疗显著增加了6μg和12μg rhBMP-2组的峰值扭转和刚度。LIPUS可促进ACS上低剂量（1.2μg和6μg）rhBMP-2诱导的骨形成和12μg剂量的骨痂成熟，用于大鼠临界尺寸股骨节段缺损的骨修复。
Bone repair is regulated by biological factors and the local mechanical environment. We hypothesize that the combined use of low intensity pulsed ultrasound (LIPUS) and recombinant human bone morphogenetic protein-2 (rhBMP-2) will synergistically or additively enhance bone regeneration in a model simulating the more difficult scenarios in orthopedic traumatology. Femoral defects in rats were replaced with absorbable collagen sponges carrying rhBMP-2 (0, 1.2, 6 or 12μg; n=30). Each group was divided equally to receive daily treatment of either LIPUS or sham stimulation. At 4 weeks new bone formation was assessed using quantitative (radiography and microcomputed tomography), qualitative (histology) and functional (biomechanical) endpoints. LIPUS with 1.2μg of rhBMP-2 significantly improved the radiographic healing as compared to its sham control starting as early as 2 weeks. Quantitatively, the use of LIPUS with 6μg of rhBMP-2 significantly increased the bone volume. However, using LIPUS with 12μg of rhBMP-2 indicated a reduction in callus size, without compromising the bone volume, which was also observable histologically, showing organized lamellar bone and repopulated marrow in the original defect region. Histologically, 1.2μg of rhBMP-2 alone showed the presence of uncalcified cartilage in the defect which was reduced with LIPUS treatment. Biomechanically, LIPUS treatment significantly increased the peak torsion and stiffness in the 6μg and 12μg rhBMP-2 group. LIPUS enhances rhBMP-2 induced bone formation at lower doses (1.2μg and 6μg) and callus maturation at 12μg dose delivered on ACS for bone repair in a rat critical-sized femoral segmental defect.