1 Otolaryngology, Skull Base Surgery and Pediatric ENT Department, Pellegrin Hospital, Bordeaux University , Bordeaux, France .
2 Inserm, U1026, Tissue Bioengineering, Bordeaux University , Bordeaux, France .
Tissue Eng Part A. 2018 May;24(9-10):703-710. doi: 10.1089/ten.TEA.2017.0095. Epub 2018 Apr 10.
Standard care for malignant tumors arising next to a bone structure is surgical removal with safety margins, followed by external beam radiotherapy (EBRT). Complete tumor removal can result in large bone defects. A two-step bone reconstruction technique using the induced membrane (IM) technique has proven its efficacy to bridge gap nonunion. During the first step, a spacer is placed in the bone gap. The spacer then is removed and the IM around it is filled with autologous cancellous bone graft. However, the feasibility of this technique with the addition of adjuvant EBRT between the two reconstruction steps has not yet been studied. Polymethyl methacrylate (PMMA) used to be the standard spacer material for the first step. Silicone spacers could replace them owing to their good behavior when submitted to EBRT and their easier removal from the surgical site during the second step. The aim of this study was to evaluate the influence of EBRT on the histological and biochemical properties of IM induced using PMMA or silicone as spacer.
The analyses were performed on PMMA- or silicone-IM with and without EBRT in a 6-mm bilateral femoral defect in 32 rats. Thickness and vessel content were measured in both groups. Bone morphogenetic protein 2 (BMP2) and vascular endothelial growth factor (VEGF) content in lysates of the crushed membranes were measured by enzyme immunoassay. Finally, alkaline phosphatase activity was analyzed in human bone marrow stromal cell cultures in contact with the same lysates.
EBRT did not change the histological structure of the cellular internal layer or the fibrous outer layer. The nature of the spacer only influenced IM thickness, PMMA-IM with external radiotherapy being significantly thicker. EBRT decreased the vascular density of IM but was less effective on VEGF/BMP2 production. In vitro, IM could have an osteoinductive potential on human bone marrow stem cells.
EBRT did not modify the histological properties of IMs but decreased their vascular density. VEGF and BMP2 production within IMs was not affected by EBRT. Silicone spacers are able to induce membranes with similar histological characteristics to PMMA-IM.
毗邻骨结构的恶性肿瘤的标准治疗方法是在安全边界下进行手术切除,然后进行外束放射治疗(EBRT)。完全切除肿瘤会导致大的骨缺损。使用诱导膜(IM)技术的两步骨重建技术已被证明可以有效地桥接非愈合间隙。在第一步中,在骨间隙中放置一个间隔物。然后取出间隔物,并用自体松质骨移植物填充其周围的 IM。然而,在两步重建之间添加辅助 EBRT 后,这种技术的可行性尚未得到研究。聚甲基丙烯酸甲酯(PMMA)曾是第一步的标准间隔物材料。由于硅酮间隔物在接受 EBRT 时表现良好,并且在第二步中更容易从手术部位取出,因此可以替代它们。本研究的目的是评估 EBRT 对使用 PMMA 或硅酮作为间隔物诱导的 IM 的组织学和生化特性的影响。
在 32 只大鼠双侧股骨 6mm 缺损中,对 PMMA 或硅酮 IM 进行了有无 EBRT 的分析。在两组中都测量了厚度和血管含量。通过酶联免疫吸附试验测量裂解膜中骨形态发生蛋白 2(BMP2)和血管内皮生长因子(VEGF)的含量。最后,分析与相同裂解物接触的人骨髓基质细胞培养物中的碱性磷酸酶活性。
EBRT 不会改变细胞内层的组织学结构或纤维外层的结构。间隔物的性质仅影响 IM 的厚度,接受外部放射治疗的 PMMA-IM 明显更厚。EBRT 降低了 IM 的血管密度,但对 VEGF/BMP2 的产生影响较小。在体外,IM 可能对人骨髓干细胞具有成骨潜能。
EBRT 不会改变 IM 的组织学特性,但会降低其血管密度。EBRT 不影响 IM 内的 VEGF 和 BMP2 产生。硅酮间隔物能够诱导具有类似于 PMMA-IM 的组织学特征的膜。