医用硫酸钙介导的Masquelet技术修复SD大鼠大段骨缺损的实验研究

发布时间：2018-04-30 14:20

本文选题：诱导膜 + 硫酸钙　；参考：《南方医科大学》2017年博士论文

【摘要】：高能量创伤、感染、骨肿瘤等导致的骨缺损是临床治疗的难点。创伤较严重且伴有严重软组织损伤或感染时,想要修复骨缺损和完成重建就更为困难。骨缺损的治疗方式包括:自体骨移植(Autologous bone graft,ABG),Ilizarov外固定牵张成骨术,带血管游离腓骨移植以及Masquelet诱导膜技术。对于5cm的骨缺损修复,多采用带血管游离腓骨移植,Ilizarov牵张成骨或Masquelet诱导膜技术。带血管游离腓骨移植技术要求较高,应力骨折和供区疼痛多见。Ilizarov牵张成骨技术易于发生针道感染、畸形愈合和神经血管损伤。Masquelet技术借助于诱导膜与自体骨移植,也存在不足:①需分次手术,骨缺损较大骨量不足时,手术间隔时间不定;②最常用的诱导膜介质聚甲基丙烯酸甲酯(Polymethylmethacrylate,PMMA)不可降解吸收,不能诱导骨修复。能否采用新的诱导膜介质医用硫酸钙(Calcium sulfate,CS),既可控降解,又能促进骨再生,修复骨缺损的同时一期完成重建?综上所述,本研究包括3部分内容。第一部分模拟Masquelet技术建立SD大鼠大段骨缺损模型研究目的:模拟Masquelet技术建立SD大鼠大段骨缺损模型。比较CS与和PMMA形成诱导膜的结构特点,观察其促成骨特性。研究方法:60只雄性SD大鼠,8孔不锈钢板制备右侧后肢股骨干10mm全段骨缺损模型。随机分为3组:CS组、PMMA组和空白对照组,每组20只。实验组分别植入CS或PMMA,空白组不植入材料。术后即刻,2,4,6和8周行X线检查,观察钢板固定及材料降解,确认模型的可行性。术后2,4,6,8周取材观察是否形成诱导膜,骨缺损样本进行组织学染色。研究结果:动物模型稳定,可行性和重复性高。CS具有良好的降解特性,PMMA未降解,两者均可以形成诱导膜。定性和定量分析两实验组的促新骨形成能力均优于空白对照组,且CS组优于PMMA组,但均未形成骨性连接。结论:模型稳定性好,成功率和可重复性高。CS既可降解又可形成诱导膜,促新骨形成能力优于PMMA。第二部分比较CS与PMMA形成诱导膜的结构特征和因子含量研究目的:比较CS与PMMA分别形成诱导膜的细胞结构和细胞因子含量,初步探讨诱导膜的促成骨机制。研究方法:40只雄性SD大鼠,造模同第一部分。分CS和PMMA组。术后2,4,6,8周取材比较诱导膜的结构特征,测定细胞因子含量,检测诱导膜中SDF-1α、CXCR-4的含量。研究结果:CS组诱导膜厚于PMMA组,两组诱导膜的结构特点相似。8周时CS诱导膜可见软骨成骨现象。诱导腆的细胞因子含量(VEGF,TGF-β1,BMP-2,ALP)随时间递增,6周达峰值后降低。不同时间点CS组的因子含量均高于PMMA组,但无显著性差异(P0.05)。不同时间点PMMA组IL-6的含量均高于CS组,2周时最高,有显著性差异(P0.05),其余各时间点无显著性差异(P0.05)。诱导膜中SDF-1α和CXCR4随时间延长而逐渐降低。结论:CS-诱导膜促成骨因子含量较高,且炎症反应较低。6周时诱导膜的成骨和成血管能力达到峰值。CS有可能替代PMMA成为新的诱导膜介质。初步揭示可能通过SDF-1α/CXCR4轴介导成骨。第三部分医用硫酸钙一期修复临界性骨缺损的动物实验研究目的:探讨CS能否一期完成临界性骨缺损的修复。研究方法:30只雄性SD大鼠,制备5mm股骨干缺损。随机分为CS组、PMMA组和空白对照组,每组10只。术后即刻、4、8、12、16、20周行X线检查,20周取材行Micro-CT检查。比较骨缺损断端的骨量和骨缺损修复情况。研究结果:术后20周,CS组的骨缺损修复形成骨性连接。PMMA组和空白对照组20周时骨缺损仍未修复。结论:CS能够促进新骨的形成,一期完成临界性骨缺损的修复。
[Abstract]:Bone defect caused by high energy trauma, infection, bone tumor and other bone defects is a difficult point in clinical treatment. It is more difficult to repair bone defects and complete reconstruction when the trauma is serious and with severe soft tissue injury or infection. The treatment of bone defect includes Autologous bone graft, ABG, Ilizarov external fixation and osteogenesis. Vascular free fibula transplantation and Masquelet induced membrane technology. For the repair of 5cm bone defects, most of the bone graft with vascular free fibula, Ilizarov distraction osteogenesis or Masquelet induced membrane technology are used. The technique of free fibula with vascular free fibula is higher, and the stress fracture and the pain of donor area are often seen by.Ilizarov distraction osteogenesis. .Masquelet technology of malunion and neurovascular injury is also deficient in the use of the induced membrane and autogenous bone graft. (1) the time interval is not definite when the bone defect is large, and the most commonly used inducible membrane medium polymethyl methacrylate (Polymethylmethacrylate, PMMA) can not be degraded and absorbable, and the bone repair can not be induced. Can the new inducible membrane medium medical calcium sulfate (Calcium sulfate, CS) be used to degrade, promote bone regeneration and repair bone defects at the same time to complete reconstruction? This study includes 3 parts. The first part simulates the purpose of modeling the large segment bone defect model in SD rats by simulating Masquelet Technology: simulated Masquelet Technology A model of large segmental bone defect in SD rats was established. The structure characteristics of CS and PMMA induced membrane were compared and the bone characteristics were observed. Methods: 60 male SD rats and 8 holes stainless steel plate were used to prepare the bone defect model of the femoral shaft of the right hind limb, and were randomly divided into 3 groups: CS group, PMMA group and blank control group, 20 rats in each group. The experimental group implanted CS or the experimental group respectively. PMMA, the blank group did not implant the material. Immediately after the operation, the X-ray examination was performed at 2,4,6 and 8 weeks. The feasibility of the model was confirmed by the fixation and the degradation of the material. 2,4,6,8 weeks after the operation, the induced membrane was formed and the bone defect samples were histologically stained. The results of the study: the animal model was stable, the feasibility and repeatability high.CS had good degradation special. Sex, PMMA did not degrade, both can form induction membrane. Qualitative and quantitative analysis of the two experimental group is superior to the blank control group, and the CS group is better than the PMMA group, but no bone connection is formed. Conclusion: the model has good stability, the success rate and the high repeatability.CS can be degraded and can form the inducible membrane, and the new bone formation ability is better than P. The second part of MMA. compared the structural characteristics and factor content of CS and PMMA induced membrane. Comparison between CS and PMMA to form the cell structure and cytokine content of the inducible membrane respectively, and preliminarily explore the mechanism of inducing bone in the induced membrane. Research methods: 40 male SD rats, the model and the first part. CS and PMMA groups. Compared with the structural characteristics of the induced membrane, the content of cytokines and the content of SDF-1 alpha and CXCR-4 in the induced membrane were detected. The results were as follows: the induced membrane in the CS group was thicker than the PMMA group. The structure characteristics of the two groups were similar to the CS induced cartilage osteogenesis in.8 weeks. The inducible cytokine content (VEGF, TGF- beta 1, BMP-2, ALP) increased with time and reached the peak of 6 weeks. The factor content of CS group at different time points was higher than that of PMMA group, but there was no significant difference (P0.05). The content of IL-6 in PMMA group at different time points was higher than that of group CS, the highest was 2 weeks, there was a significant difference (P0.05), there was no significant difference between the other time points (P0.05). The induction of SDF-1 alpha and CXCR4 gradually decreased with time. Conclusion: CS- induction The membrane contributes to the high bone factor, and the inflammatory response is low at.6 weeks. The induced membrane osteogenesis and the ability to reach the peak value.CS may replace the PMMA to become a new inducible membrane medium. It is preliminarily revealed that the osteogenesis may be mediated through the SDF-1 alpha /CXCR4 axis. The objective of the experimental study on the first phase of the repair of the boundary bone defect in the third part of medical calcium sulfate To discuss whether CS could complete the repair of critical bone defect at one stage. Methods: 30 male SD rats were prepared for the preparation of 5mm femoral shaft defects. They were randomly divided into CS group, PMMA group and blank control group, with 10 rats in each group. The X-ray examination was performed immediately after the operation, and the Micro-CT examination was performed at 20 weeks. The bone defect and bone defect repair of the bone defect were compared. Results: 20 weeks after operation, bone defect in group CS was repaired to form bone connection.PMMA group and blank control group for 20 weeks. Conclusion: CS could promote the formation of new bone and complete the repair of critical bone defect in one stage.

【学位授予单位】：南方医科大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R687.3

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