Inflammatory Characteristics of rhBMP-2 In Vitro and in an In Vivo Rodent Model
Inflammatory Characteristics of rhBMP-2 In Vitro and in an In Vivo Rodent Model
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DOI：
10.1097/brs.0b013e3181f2d1ec
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发表时间：
2011-02-01
期刊：
影响因子：
3
通讯作者：
Wang, Jeffrey C.
中科院分区：
文献类型：
--
作者：
Lee, Kwang-Bok;Taghavi, Cyrus E.;Wang, Jeffrey C.
研究设计：体内和体外模型。
目的：研究重组人骨形态发生蛋白 - 2（rhBMP - 2）引起的软组织炎症。
背景资料概述：尽管rhBMP - 2在脊柱融合方面效果极佳，但在颈部使用时会出现吞咽困难和呼吸功能受损的情况。肿胀和炎症反应的机制尚未完全阐明。
方法：采用酶联免疫吸附测定（ELISA）试剂盒（白细胞介素 - 6、白细胞介素 - 10、肿瘤坏死因子 - α）测量不同浓度rhBMP - 2下的细胞因子水平。将可吸收胶原海绵在有或无不同浓度rhBMP - 2的情况下，皮下（SC）和肌内（IM）植入大鼠背部。在3小时以及2、4和7天使用磁共振成像测量炎症。使用MIPAV软件测量并比较炎症体积。7天后处死大鼠并进行研究。
结果：白细胞介素 - 6、白细胞介素 - 10和肿瘤坏死因子 - α的释放呈剂量依赖性。rhBMP - 2植入后的软组织水肿也呈剂量依赖性，皮下植入后在3小时达到峰值（无论是皮下还是肌内植入），肌内植入后在第2天达到峰值。皮下植入后均形成肉芽肿样肿块。在10μg/10μL和20μg/10μL（高浓度）组中肿块大得多。炎症反应未扩散穿过生理屏障（皮下筋膜）。两个高剂量组均伴有包膜下血肿以及炎症区域显著增大。
结论：使用rhBMP - 2后的肿胀和炎症呈剂量依赖性。肿胀可能是由于直接接触以及在植入平面扩散所致。原因是强烈的炎症反应以及无菌血清肿和包膜下血肿的形成。
Study Design. In vivo and in vitro model. Objective. Investigate soft-tissue inflammation caused by rhBMP-2.Summary of Background Data. Although rhBMP-2 produces excellent rates of fusion in the spine, dysphagia and respiratory compromise have occurred when used in the neck. The mechanism of the swelling and inflammatory response has yet to be fully elucidated.Methods. ELISA kits (IL-6, IL-10, TNF-alpha) were used to measure cytokine levels at different concentrations of rhBMP-2. Absorbable collagen sponges were implanted with or without different concentrations of rhBMP-2 into the backs of rats subcutaneously (SC) and intramuscularly (IM). Magnetic resonance imaging was used to measure inflammation at 3 hours and 2, 4, and 7 days. The inflammatory volumes were measured and compared using MIPAV software. Rats were killed after 7 days and studied.Results. IL-6, IL-10, and TNF-alpha release was dose-dependent. Soft-tissue edema after rhBMP-2 implantation was also dose-dependent, peaking at 3 hours SC, after SC and IM implantations, and on day 2 IM after IM implantation. All formed a granuloma-type mass after SC insertion. The mass was much larger in the 10 and 20 mu g/10 mu L (high-concentration) groups. The inflammatory response did not diffuse across physiologic barriers (subcutaneous fascia). Both high-dose groups were associated with encapsulated hematomas and a significant increase in the inflammatory zone.Conclusion. Swelling and inflammation after rhBMP-2 use are dose-dependent. Swelling may be due to direct contact as well as spread in the plane of access. The causes are a robust inflammatory reaction as well as sterile seroma and encapsulated hematoma formation.