Bone Marrow Enhances the Performance of rhBMP-2 in Spinal Fusion A Rodent Model
Bone Marrow Enhances the Performance of rhBMP-2 in Spinal Fusion A Rodent Model
复制标题
DOI：
10.2106/jbjs.k.01118
复制
发表时间：
2013-02-20
影响因子：
5.3
通讯作者：
Delamarter, Rick B.
中科院分区：
文献类型：
--
作者：
Bae, Hyun W.;Zhao, Li;Delamarter, Rick B.
背景：可靠和快速的骨形成是生物制剂和基于细胞的脊柱融合技术的目标。虽然没有基于细胞的单独治疗是成功的，但重组人骨形态发生蛋白-2（rhBMP-2）自2002年被美国食品和药物管理局（FDA）批准以来，已成功用于接受各种脊柱融合手术的广泛患者。然而，问题仍然是如何提高rhBMP-2的生物学效率或骨诱导性，以成功应用于最具挑战性的脊柱融合患者或减少目前所需的剂量。本研究探讨如何通过添加新鲜收获的骨髓穿刺液（BMA）调节rhBMP-2 efficiency.Methods：一个L4-L5后外侧横突间脊柱融合程序进行刘易斯大鼠的细胞环境。植入物的亚有效浓度为0.006 mg/mL rhBMP-2/两个可吸收胶原海绵（ACS）加直接应用的新鲜同系BMA移植物（n = 18）、0.006 mg/mL rhBMP-2/两个ACS/侧（n = 12）、0.006 mg/mL rhBMP-2/一个ACS/侧（n = 12）或BMA/一个ACS/侧（n = 6）。在第8周处死大鼠，并使用手动触诊、X线片和生物力学测试进行评估。BMA +0.006 mg/mL rhBMP-2/ACS显著增加L4-L5融合率至89%（16/18），而基础融合率为33%对于植入rhBMP-2/ACS的大鼠，强度或刚度从10%（12只中的4只）到50%（12只中的6只）（p < 0.05），在条件之间没有差异。在6只接受BMA/ACS的大鼠中没有观察到融合或骨形成。结论：当与BMA混合时，需要较少的rhBMP-2才能发挥作用。当BMA与rhBMP-2混合时，融合率增加了近两倍。在融合强度或刚度方面没有改善。临床相关性：BMA和rhBMP-2等佐剂可提高融合成功率，在多节段脊柱手术中显著减少每个节段的剂量，节省成本和/或减少剂量相关并发症。这在临床实施之前需要进一步研究。
Background: Reliable and rapid bone formation is the goal of biologics and cell-based spinal fusion technologies. While no cell-based therapy alone has been successful, recombinant human bone morphogenetic protein-2 (rhBMP-2) has been successfully used in a wide spectrum of patients undergoing a variety of spinal fusion procedures since its approval by the United States Food and Drug Administration (FDA) in 2002. However, the question remains how to improve the biologic efficiency, or osteoinductivity, of rhBMP-2 for successful application in the most challenging patients undergoing spinal fusion or to reduce the doses currently required. The present study investigated how varying the cellular environments through the addition of freshly harvested bone marrow aspirate (BMA) modulates rhBMP-2 efficiency.Methods: An L4-L5 posterolateral intertransverse process spinal fusion procedure was performed in Lewis rats. The implants were a subeffective concentration of 0.006 mg/mL of rhBMP-2/two absorbable collagen sponges (ACS) plus directly applied fresh syngeneic BMA transplants (n = 18), 0.006-mg/mL rhBMP-2/two ACS/side (n = 12), 0.006-mg/mL rhBMP-2/one ACS/side (n = 12), or BMA/one ACS/side (n = 6). Rats were killed at eight weeks and were evaluated with use of manual palpation, radiographs, and biomechanical testing.Results: BMA plus 0.006-mg/mL rhBMP-2/ACS significantly increased the L4-L5 fusion rate to 89% (sixteen of eighteen) compared with a base fusion rate of 33% (four of twelve) to 50% (six of twelve) for rats implanted with rhBMP-2/ACS (p < 0.05), with no difference in strength or stiffness between conditions. No fusion or bone formation was observed in the six rats that received BMA/ACS alone.Conclusions: Less rhBMP-2 was needed for effect when mixed with BMA. A nearly twofold increase in the fusion rate was found when BMA was mixed with a deliberate subeffective concentration of rhBMP-2. There was no improvement in terms of fusion strength or stiffness. Clinical Relevance: Adjuvants such as BMA with rhBMP-2 may improve fusion success, allow marked dose reduction per segment in multilevel spinal surgery, result in cost savings, and/or decrease dose-related complications. This warrants further study prior to clinical implementation.