Khan Safdar N, Toth Jeffrey M, Gupta Kavita, Glassman Steven D, Gupta Munish C
*Department of Orthopaedic Surgery, Division of Spine Surgery, The Ohio State University, Columbus, OH †Department of Orthopaedic Surgery, Spine Service, University of California, Davis, CA ‡Department of Orthopaedic Surgery, Medical College of Wisconsin §Colleges of Dentistry and Engineering, Marquette University, Milwaukee, WI ∥Department of Orthopaedic Surgery, University of Louisville, Louisville, KY.
J Spinal Disord Tech. 2014 Jun;27(4):212-9. doi: 10.1097/BSD.0b013e3182767c67.
We used a nonhuman primate lumbar intertransverse process arthrodesis model to evaluate biological cascade of bone formation using different carrier preparation methods with a single dose of recombinant human bone morphogenetic protein-2 (rhBMP-2) at early time points.
To examine early-term/mid-term descriptive histologic and computerized tomographic events in single-level uninstrumented posterolateral nonhuman primate spinal fusions using rhBMP-2/absorbable collagen sponge (ACS) combined with ceramic bulking agents in 3 different configurations.
rhBMP-2 on an ACS carrier alone leads to consistent posterolateral lumbar spine fusions in lower-order animals; however, these results have been difficult to replicate in nonhuman primates.
Twelve skeletally mature, rhesus macaque monkeys underwent single-level posterolateral arthrodesis at L4-L5. A hydroxyapatite/β-tricalcium phosphate ceramic bulking agent in 3 formulations was used in the treatment groups (n=3). When used, rhBMP-2/ACS at 1.5 mg/cm (3.0 mg rhBMP-2) was combined with 2.5 cm of ceramic bulking agent per side. Animals were euthanized at 4 and 12 weeks postoperative. Computerized tomography scans were performed immediately postoperatively and every 4 weeks until they were euthanized. Sagittal histologic sections were evaluated for bone histogenesis and location, cellular infiltration of the graft/substitute, and bone remodeling activity.
Significant histologic differences in the developing fusion appeared between the 3 rhBMP-2/ACS treatment groups at 4 and 12 weeks. At 4 weeks, bone formation appeared to originate at the transverse process and the intertransverse membrane. Cellular infiltration was greatest in granular ceramic groups compared with matrix ceramic group. Minimal to no residual ACS was identified at the early time point. At 12 weeks, marked ceramic remodeling was observed with continued bone formation noted in all carrier groups.
At the early time period, histology showed that bone formation appeared to originate at the transverse processes and the intertransverse membrane, indicating that the dorsal muscle bed may not be the only location for bone formation. Histology also showed that the collagen carrier for rhBMP-2 is mostly resorbed by 4 weeks. Our results and previous literature indicate that ceramic bulking agents are needed to provide resistance to compression caused by paraspinal muscles on the fusion bed in the posterolateral environment. Histology showed that ceramic bulking agents may offer long-term scaffolding and a structure to supporting bone formation of the developing fusion mass.
我们使用非人类灵长类动物腰椎横突间关节融合模型，在早期时间点采用不同的载体制备方法并单次使用重组人骨形态发生蛋白-2（rhBMP-2）来评估骨形成的生物学级联反应。
使用rhBMP-2/可吸收胶原海绵（ACS）并结合3种不同构型的陶瓷填充剂，研究非人类灵长类动物单节段无内固定后外侧脊柱融合术中的早期/中期描述性组织学和计算机断层扫描情况。
单独使用ACS载体上的rhBMP-2可在低等动物中实现一致的腰椎后外侧融合；然而，这些结果在非人类灵长类动物中难以复制。
1十二只骨骼成熟的恒河猴在L4-L5节段接受单节段后外侧关节融合术。治疗组（n = 3）使用3种配方的羟基磷灰石/β-磷酸三钙陶瓷填充剂。使用时，1.5mg/cm（3.0mg rhBMP-2）的rhBMP-2/ACS与每侧2.5cm的陶瓷填充剂联合使用。动物在术后4周和12周实施安乐死。术后立即进行计算机断层扫描，并每4周进行一次，直至实施安乐死。对矢状面组织学切片进行评估，以观察骨组织发生情况及位置、移植物/替代物的细胞浸润情况以及骨重塑活性。
在4周和12周时，3个rhBMP-2/ACS治疗组之间在融合发育过程中出现了显著的组织学差异。在4周时，骨形成似乎起源于横突和横突间膜。与基质陶瓷组相比，颗粒状陶瓷组的细胞浸润最为明显。在早期时间点，仅发现极少的残余ACS或未发现残余ACS。在12周时，观察到明显的陶瓷重塑，且所有载体组均持续有骨形成。
在早期阶段，组织学显示骨形成似乎起源于横突和横突间膜，这表明背侧肌床可能不是骨形成的唯一部位。组织学还显示，rhBMP-2的胶原载体在4周时大多已被吸收。我们的结果和先前的文献表明，需要陶瓷填充剂来抵抗后外侧环境中椎旁肌对融合床造成的压缩。组织学显示，陶瓷填充剂可能提供长期支架结构，并为发育中的融合块的骨形成提供支撑结构。
