y Towards Understanding Therapeutic Failures in Masquelet Surgery: First Evidence that Defective Induced Membrane Properties are Associated with Clinical Failures
y Towards Understanding Therapeutic Failures in Masquelet Surgery: First Evidence that Defective Induced Membrane Properties are Associated with Clinical Failures
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DOI：
10.3390/jcm9020450
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发表时间：
2020-02-01
影响因子：
3.9
通讯作者：
Collombet, Jean-Marc
中科院分区：
文献类型：
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作者：
Durand, Marjorie;Barbier, Laure;Collombet, Jean-Marc
两阶段Masqulet诱导膜技术(IMT)包括骨水泥间隔驱动的膜诱导，然后在膜内植入自体松质骨，以促进大段骨缺损的修复。这项研究首次旨在将IMT失败与患者诱导膜(IM)的生理性改变联系起来。为此，我们比较了从IM收集的各种组织学、免疫组织化学和基因表达参数，这些患者最近被归类为成功(响应者；n=8)或不成功(无响应者；n=3)，采用Masqulet技术(术后6个月临床和放射学随访)。尽管与应答者IM相比，无反应者IM的血管生成或巨噬细胞分布模式没有改变，但我们发现无应答者IM中缺少间充质干细胞，成纤维细胞样细胞密度降低。此外，无反应者IM显示细胞外基质(ECM)重构参数改变，如金属蛋白酶-9(MMP9)/金属蛋白酶组织抑制因子-1(TIMP-1)的mRNA表达比率降低，以及重要的胶原蛋白过度表达。总之，这项研究首次报道了IMT失败与IM特性缺陷有关的证据，同时强调了ECM重塑参数的重要性，特别是MMP-9/TIMP-1基因表达比率，作为IMT预后的早期预测生物标记物，无论骨骼类型、骨折类型或患者特征如何。
The two-stage Masquelet induced-membrane technique (IMT) consists of cement spacer-driven membrane induction followed by an autologous cancellous bone implantation in this membrane to promote large bone defect repairs. For the first time, this study aims at correlating IMT failures with physiological alterations of the induced membrane (IM) in patients. For this purpose, we compared various histological, immunohistochemical and gene expression parameters obtained from IM collected in patients categorized lately as successfully (Responders; n = 8) or unsuccessfully (Non-responders; n = 3) treated with the Masquelet technique (6 month clinical and radiologic post-surgery follow-up). While angiogenesis or macrophage distribution pattern remained unmodified in non-responder IM as compared to responder IM, we evidenced an absence of mesenchymal stem cells and reduced density of fibroblast-like cells in non-responder IM. Furthermore, non-responder IM exhibited altered extracellular matrix (ECM) remodeling parameters such as a lower expression ratio of metalloproteinase-9 (MMP-9)/tissue inhibitor of metalloproteinases (TIMP-1) mRNA as well as an important collagen overexpression as shown by picrosirius red staining. In summary, this study is the first to report evidence that IMT failure can be related to defective IM properties while underlining the importance of ECM remodeling parameters, particularly the MMP-9/TIMP-1 gene expression ratio, as early predictive biomarkers of the IMT outcome regardless of the type of bone, fracture or patient characteristics.