Repairing mandibular bone defects after radiotherapy of the upper aerodigestive tract is clinically challenging. Although bone tissue engineering has recently generated a number of innovative treatment approaches for osteoradionecrosis (ORN), these modalities must be evaluated preclinically in a relevant, reproducible, animal model. The objective of this study was to evaluate a novel rat model of mandibular irradiation sequelae, with a focus on the adverse effects of radiotherapy on bone structure, intraosseous vascularization, and bone regeneration. Rats were irradiated with a single 80 Gy dose to the jaws. Three weeks after irradiation, mandibular bone defects of different sizes (0, 1, 3, or 5 mm) were produced in each hemimandible. Five weeks after the surgical procedure, the animals were euthanized. Explanted mandibular samples were qualitatively and quantitatively assessed for bone formation, bone structure, and intraosseous vascular volume by using micro-computed tomography, scanning electron microscopy, and histology. Twenty irradiated hemimandibles and 20 nonirradiated hemimandibles were included in the study. The bone and vessel volumes were significantly lower in the irradiated group. The extent of bone remodeling was inversely related to the defect size. In the irradiated group, scanning electron microscopy revealed a large number of polycyclic gaps consistent with periosteocytic lysis (described as being pathognomonic for ORN). This feature was correlated with elevated osteoclastic activity in a histological assessment. In the irradiated areas, the critical-sized defect was 3 mm. Hence, our rat model of mandibular irradiation sequelae showed hypovascularization and osteopenia.

中文翻译：

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用于骨修复临床前研究的下颌骨照射后遗症大鼠模型的开发。

在上呼吸消化道放疗后修复下颌骨缺损在临床上具有挑战性。尽管骨组织工程最近产生了许多治疗放射性骨坏死 (ORN) 的创新方法，但必须在相关的、可重复的动物模型中对这些方法进行临床前评估。本研究的目的是评估一种新的下颌骨照射后遗症大鼠模型，重点关注放疗对骨结构、骨内血管化和骨再生的不利影响。大鼠下颌接受单次 80 Gy 剂量照射。照射后三周，每个半下颌骨产生不同大小（0、1、3 或 5 毫米）的下颌骨缺损。外科手术后五周，对动物实施安乐死。通过使用显微计算机断层扫描、扫描电子显微镜和组织学对骨形成、骨结构和骨内血管体积进行定性和定量评估。研究中包括了 20 个辐照过的半下颌和 20 个未辐照的半下颌。照射组的骨和血管体积显着降低。骨重建的程度与缺损大小呈负相关。在照射组中，扫描电子显微镜显示大量多环间隙与骨膜细胞溶解一致（被描述为 ORN 的特征）。该特征与组织学评估中的破骨细胞活性升高相关。在照射区域，临界尺寸缺陷为 3 mm。因此，