A Novel Murine Femoral Segmental Critical-Sized Defect Model Stabilized by Plate Osteosynthesis for Bone Tissue Engineering Purposes
A Novel Murine Femoral Segmental Critical-Sized Defect Model Stabilized by Plate Osteosynthesis for Bone Tissue Engineering Purposes
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DOI：
10.1089/ten.tec.2012.0256
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发表时间：
2013-04-01
影响因子：
3
通讯作者：
Petite, Herve
中科院分区：
文献类型：
--
作者：
Manassero, Mathieu;Viateau, Veronique;Petite, Herve
小鼠模型是研究导致萎缩性骨不连的大骨缺损愈合过程的机制和疗效的宝贵工具，这是一个严重的医疗问题和与医疗保健相关的经济负担。萎缩性骨不连模型通常通过提供高度稳定的生物力学环境来实现。为此，外固定器已被研究，但钢板接骨术，尽管其高度的临床意义，尚未被认为是在小鼠。我们在此提出并研究了使用内固定术来稳定大面积骨缺损。为此，使用Gigli锯和夹具在股骨中段诱导3.5 mm长的节段性骨缺损。使用钛制微型锁定接骨板和4枚锁定螺钉进行骨固定。骨缺损要么空着，要么用同源骨移植物填充，要么用珊瑚支架填充。使用X线片监测愈合情况。术后10周，使用显微计算机断层扫描和组织学进一步评估愈合过程。除一只小鼠在手术过程中死亡外，未观察到并发症。在所有受试动物中均获得了稳定且可重现的骨固定以及植入材料的可重现固定，并完全承重。骨不连在骨缺损留空的组中持续观察到。使用同源骨移植物获得了骨愈合，提供了证据表明，尽管此类缺损具有临界尺寸，但当使用金标准材料填充缺损时，骨愈合是可能的。虽然珊瑚支架组的新骨形成比空动物组的新骨形成更多，但它仍然有限，并且位于骨边缘附近，这是这种骨缺损的临界尺寸的结果。我们的研究建立了一个可重复的，临床相关的，股骨，萎缩性骨不连，临界尺寸的缺损，低发病率的小鼠模型。本研究在小动物模型中成功设计和测试了一种用于评估骨修复的新型手术方法;该模型有可能促进研究承重节段性骨缺损中骨再生所涉及的分子和细胞事件。
Mouse models are invaluable tools for mechanistic and efficacy studies of the healing process of large bone defects resulting in atrophic nonunions, a severe medical problem and a financial health-care-related burden. Models of atrophic nonunions are usually achieved by providing a highly stable biomechanical environment. For this purpose, external fixators have been investigated, but plate osteosynthesis, despite its high clinical relevance, has not yet been considered in mice. We hereby proposed and investigated the use of an internal osteosynthesis for stabilizing large bone defects. To this aim, a 3.5-mm-long segmental bone defect was induced in the mid-shaft of the femur using a Gigli saw and a jig. Bone fixation was performed using a titanium microlocking plate with four locking screws. The bone defect was either left empty or filled with a syngenic bone graft or filled with a coralline scaffold. Healing was monitored using radiographs. The healing process was further assessed using microcomputed tomography and histology 10 weeks after surgery. With the exception of one mouse that died during the surgical procedure, no complications were observed. A stable and reproducible bone fixation as well as a reproducible fixation of the implanted materials with full weight bearing was obtained in all animals tested. Nonunion was consistently observed in the group in which the defects were left empty. Bone union was obtained with the syngenic bone grafts, providing evidence that, although such defects were of critical size, bone healing was possible when the gold-standard material was used to fill the defect. Although new bone formation was greater in the coralline scaffold group than in the left-empty animal group, it remained limited and localized close to the bony edges, a consequence of the critical size of such bone defect. Our study established a reproducible, clinically relevant, femoral, atrophic nonunion, critical-sized defect, low morbidity mouse model. The present study was successful in designing and testing in a small animal model, a novel surgical method for the assessment of bone repair; this model has the potential to facilitate investigations of the molecular and cellular events involved in bone regeneration in load-bearing, segmental-bone defects.