Spine Center, Division of Orthopaedic Surgery, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
J Bone Joint Surg Am. 2012 Oct 17;94(20):1845-52. doi: 10.2106/JBJS.K.00469.
Recombinant human bone morphogenetic protein-2 (rhBMP-2) is an osteoinductive protein. However, soft-tissue edema adjacent to the site of rhBMP-2 implantation has been reported. This animal study was designed to examine soft-tissue edema associated with increasing rhBMP-2 doses with implantation on an absorbable collagen sponge (ACS) and with injection directly into muscle.
Thirty-six Lewis rats received intramuscular implantation of rhBMP-2 on an ACS (Part I) or intramuscular injection of rhBMP-2 solution (Part II). Part-I sites received rhBMP-2/ACS at doses of 0 μg, 30 μg (normal), 129 μg (mid), or 450 μg (high). Part-II sites received rhBMP-2/ACS or rhBMP-2 intramuscular injection at doses of 10 μg (normal) or 150 μg (mid). A previous rat model showed 10 μg to be 100% effective at inducing osseous spinal fusion. In our study, T2-weighted magnetic resonance imaging (MRI) was performed at two and seven days to assess edema volume, and statistical comparisons were carried out with analysis of variance (ANOVA). Cellular response, vascularity, and ossification were examined histologically.
Quantitative MRI demonstrated similar peri-implant edema volumes in the control (buffer on an ACS) and normal-dose rhBMP-2 groups. Higher doses resulted in increased edema volume. Edema decreased significantly from two to seven days. Similar capillary densities were observed in all rhBMP-2 groups at two days, and there was dose-dependent increased ossification at seven days. Compared with the rhBMP-2 injection, implantation of the rhBMP-2/ACS resulted in increased edema. This edematous response was transient in all groups. Minimal or no ossification occurred after the rhBMP-2 injections.
Transient peri-implant soft-tissue edema occurred in a dose-dependent manner following implantation of rhBMP-2/ACS in this rat model. The normal dose of rhBMP-2/ACS produced edema similar to that in the controls. Finally, rhBMP-2 solutions injected directly into muscle resulted in minimal soft-tissue edema.
重组人骨形态发生蛋白-2（rhBMP-2）是一种骨诱导蛋白。然而，已有报道称 rhBMP-2 植入部位周围出现软组织水肿。本动物研究旨在探讨 rhBMP-2 剂量增加与植入可吸收胶原海绵（ACS）和直接肌肉注射相关的软组织水肿。
36 只 Lewis 大鼠接受 rhBMP-2/ACS 肌肉内植入（第一部分）或 rhBMP-2 溶液肌肉内注射（第二部分）。第一部分的植入部位接受 rhBMP-2/ACS 的剂量分别为 0 μg、30 μg（正常）、129 μg（中）或 450 μg（高）。第二部分的植入部位接受 rhBMP-2/ACS 或 rhBMP-2 肌肉内注射的剂量分别为 10 μg（正常）或 150 μg（中）。先前的大鼠模型显示 10 μg 可 100%有效诱导骨融合。在我们的研究中，在第 2 天和第 7 天进行 T2 加权磁共振成像（MRI）以评估水肿体积，并通过方差分析（ANOVA）进行统计比较。组织学检查细胞反应、血管生成和骨化。
定量 MRI 显示对照（ACS 上的缓冲液）和正常剂量 rhBMP-2 组的周围植入物水肿体积相似。较高剂量导致水肿体积增加。水肿从第 2 天到第 7 天显著减少。在所有 rhBMP-2 组中，在第 2 天观察到相似的毛细血管密度，并且在第 7 天观察到剂量依赖性的骨化增加。与 rhBMP-2 注射相比，rhBMP-2/ACS 的植入导致水肿增加。在所有组中，这种水肿反应都是短暂的。rhBMP-2 注射后几乎没有或没有骨化发生。
在该大鼠模型中，rhBMP-2/ACS 植入后，软组织水肿呈剂量依赖性发生。rhBMP-2/ACS 的正常剂量产生的水肿与对照组相似。最后，直接肌肉注射 rhBMP-2 溶液导致软组织水肿最小。
