Quantifying Vascular Changes Surrounding Bone Regeneration in a Porcine Mandibular Defect Using Computed Tomography
Quantifying Vascular Changes Surrounding Bone Regeneration in a Porcine Mandibular Defect Using Computed Tomography
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DOI：
10.1089/ten.tec.2019.0205
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发表时间：
2019-12-01
影响因子：
3
通讯作者：
Guda, Teja
中科院分区：
文献类型：
--
作者：
Carlisle, Patricia;Marrs, Jeffrey;Guda, Teja
血管生成是最佳骨愈合所必需的关键过程。一些体外和体内系统先前已被用来阐明血管生成过程中涉及的一些机制，同时测试在新血管形成中发挥重要作用的潜在治疗剂和生物活性因子。计算机断层扫描 (CT) 是一种无创成像技术，最近使研究人员能够获得各种高分辨率、三维结构特征，例如骨缺损内的骨形成。不幸的是，迄今为止，血管生成评估主要依赖于组织学或离体成像，很少有研究利用 CT 来定性和定量研究骨修复过程中的血管反应。在当前的研究中，使用基于临床 CT 的技术来评估 rhBMP-2 洗脱移植物治疗对小型猪下颌骨大节段骨缺损模型周围软组织血管结构的影响。本研究的目的是证明对比增强临床 64 层 CT 技术在提取 12 周内血管结构定量指标方面的功效。这项研究的结果表明，rhBMP-2 的存在对 4 至 12 周的血管体积产生积极影响，这是因为血管数量同时增加，而 rhBMP-2 治疗的 4 周时血管数量也显着增加。更重要的是，血管结构分析显示在整个研究期间没有变化，表明治疗安全。这项研究验证了 CT 分析作为一种相关成像方法，用于定量和定性分析骨愈合部位周围血管组织的形态特征。同样重要的是，该研究表明 CT 技术可用于大型动物模型，并有可能转化为临床模型，以开发改进的方法来评估治疗过程中的组织愈合和血管适应过程。该方法已证明对跟踪血管化的空间和时间变化具有敏感性，并且也有可能应用于研究其他高对比度组织的变化。
Angiogenesis is a critical process essential for optimal bone healing. Several in vitro and in vivo systems have been previously used to elucidate some of the mechanisms involved in the process of angiogenesis, and at the same time, to test potential therapeutic agents and bioactive factors that play important roles in neovascularization. Computed tomography (CT) is a noninvasive imaging technique that has recently allowed investigators to obtain a diverse range of high-resolution, three-dimensional characterization of structures, such as bone formation within bony defects. Unfortunately, to date, angiogenesis evaluation relies primarily on histology, or ex vivo imaging and few studies have utilized CT to qualitatively and quantitatively study the vascular response during bone repair. In the current study a clinical CT-based technique was used to evaluate the effects of rhBMP-2 eluting graft treatment on soft tissue vascular architecture surrounding a large segmental bone defect model in the minipig mandible. The objective of this study was to demonstrate the efficacy of contrast-enhanced, clinical 64-slice CT technology in extracting quantitative metrics of vascular architecture over a 12-week period. The results of this study show that the presence of rhBMP-2 had a positive effect on vessel volume from 4 to 12 weeks, which was explained by a concurrent increase in vessel number, which was also significantly higher at 4 weeks for the rhBMP-2 treatment. More importantly, analysis of vessel architecture showed no changes throughout the duration of the study, indicating therapeutic safety. This study validates CT analysis as a relevant imaging method for quantitative and qualitative analysis of morphological characteristics of vascular tissue around a bone healing site. Also important, the study shows that CT technology can be used in large animal models and potentially be translated into clinical models for the development of improved methods to evaluate tissue healing and vascular adaptation processes over the course of therapy. This methodology has demonstrated sensitivity to tracking spatial and temporal changes in vascularization and has the potential to be applied to studying changes in other high-contrast tissues as well.