醫(yī)用硫酸鈣介導(dǎo)的Masquelet技術(shù)修復(fù)SD大鼠大段骨缺損的實(shí)驗(yàn)研究
本文選題:誘導(dǎo)膜 + 硫酸鈣; 參考:《南方醫(yī)科大學(xué)》2017年博士論文
【摘要】:高能量創(chuàng)傷、感染、骨腫瘤等導(dǎo)致的骨缺損是臨床治療的難點(diǎn)。創(chuàng)傷較嚴(yán)重且伴有嚴(yán)重軟組織損傷或感染時(shí),想要修復(fù)骨缺損和完成重建就更為困難。骨缺損的治療方式包括:自體骨移植(Autologous bone graft,ABG),Ilizarov外固定牽張成骨術(shù),帶血管游離腓骨移植以及Masquelet誘導(dǎo)膜技術(shù)。對于5cm的骨缺損修復(fù),多采用帶血管游離腓骨移植,Ilizarov牽張成骨或Masquelet誘導(dǎo)膜技術(shù)。帶血管游離腓骨移植技術(shù)要求較高,應(yīng)力骨折和供區(qū)疼痛多見。Ilizarov牽張成骨技術(shù)易于發(fā)生針道感染、畸形愈合和神經(jīng)血管損傷。Masquelet技術(shù)借助于誘導(dǎo)膜與自體骨移植,也存在不足:①需分次手術(shù),骨缺損較大骨量不足時(shí),手術(shù)間隔時(shí)間不定;②最常用的誘導(dǎo)膜介質(zhì)聚甲基丙烯酸甲酯(Polymethylmethacrylate,PMMA)不可降解吸收,不能誘導(dǎo)骨修復(fù)。能否采用新的誘導(dǎo)膜介質(zhì)醫(yī)用硫酸鈣(Calcium sulfate,CS),既可控降解,又能促進(jìn)骨再生,修復(fù)骨缺損的同時(shí)一期完成重建?綜上所述,本研究包括3部分內(nèi)容。第一部分模擬Masquelet技術(shù)建立SD大鼠大段骨缺損模型研究目的:模擬Masquelet技術(shù)建立SD大鼠大段骨缺損模型。比較CS與和PMMA形成誘導(dǎo)膜的結(jié)構(gòu)特點(diǎn),觀察其促成骨特性。研究方法:60只雄性SD大鼠,8孔不銹鋼板制備右側(cè)后肢股骨干10mm全段骨缺損模型。隨機(jī)分為3組:CS組、PMMA組和空白對照組,每組20只。實(shí)驗(yàn)組分別植入CS或PMMA,空白組不植入材料。術(shù)后即刻,2,4,6和8周行X線檢查,觀察鋼板固定及材料降解,確認(rèn)模型的可行性。術(shù)后2,4,6,8周取材觀察是否形成誘導(dǎo)膜,骨缺損樣本進(jìn)行組織學(xué)染色。研究結(jié)果:動(dòng)物模型穩(wěn)定,可行性和重復(fù)性高。CS具有良好的降解特性,PMMA未降解,兩者均可以形成誘導(dǎo)膜。定性和定量分析兩實(shí)驗(yàn)組的促新骨形成能力均優(yōu)于空白對照組,且CS組優(yōu)于PMMA組,但均未形成骨性連接。結(jié)論:模型穩(wěn)定性好,成功率和可重復(fù)性高。CS既可降解又可形成誘導(dǎo)膜,促新骨形成能力優(yōu)于PMMA。第二部分比較CS與PMMA形成誘導(dǎo)膜的結(jié)構(gòu)特征和因子含量研究目的:比較CS與PMMA分別形成誘導(dǎo)膜的細(xì)胞結(jié)構(gòu)和細(xì)胞因子含量,初步探討誘導(dǎo)膜的促成骨機(jī)制。研究方法:40只雄性SD大鼠,造模同第一部分。分CS和PMMA組。術(shù)后2,4,6,8周取材比較誘導(dǎo)膜的結(jié)構(gòu)特征,測定細(xì)胞因子含量,檢測誘導(dǎo)膜中SDF-1α、CXCR-4的含量。研究結(jié)果:CS組誘導(dǎo)膜厚于PMMA組,兩組誘導(dǎo)膜的結(jié)構(gòu)特點(diǎn)相似。8周時(shí)CS誘導(dǎo)膜可見軟骨成骨現(xiàn)象。誘導(dǎo)腆的細(xì)胞因子含量(VEGF,TGF-β1,BMP-2,ALP)隨時(shí)間遞增,6周達(dá)峰值后降低。不同時(shí)間點(diǎn)CS組的因子含量均高于PMMA組,但無顯著性差異(P0.05)。不同時(shí)間點(diǎn)PMMA組IL-6的含量均高于CS組,2周時(shí)最高,有顯著性差異(P0.05),其余各時(shí)間點(diǎn)無顯著性差異(P0.05)。誘導(dǎo)膜中SDF-1α和CXCR4隨時(shí)間延長而逐漸降低。結(jié)論:CS-誘導(dǎo)膜促成骨因子含量較高,且炎癥反應(yīng)較低。6周時(shí)誘導(dǎo)膜的成骨和成血管能力達(dá)到峰值。CS有可能替代PMMA成為新的誘導(dǎo)膜介質(zhì)。初步揭示可能通過SDF-1α/CXCR4軸介導(dǎo)成骨。第三部分醫(yī)用硫酸鈣一期修復(fù)臨界性骨缺損的動(dòng)物實(shí)驗(yàn)研究目的:探討CS能否一期完成臨界性骨缺損的修復(fù)。研究方法:30只雄性SD大鼠,制備5mm股骨干缺損。隨機(jī)分為CS組、PMMA組和空白對照組,每組10只。術(shù)后即刻、4、8、12、16、20周行X線檢查,20周取材行Micro-CT檢查。比較骨缺損斷端的骨量和骨缺損修復(fù)情況。研究結(jié)果:術(shù)后20周,CS組的骨缺損修復(fù)形成骨性連接。PMMA組和空白對照組20周時(shí)骨缺損仍未修復(fù)。結(jié)論:CS能夠促進(jìn)新骨的形成,一期完成臨界性骨缺損的修復(fù)。
[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.
【學(xué)位授予單位】:南方醫(yī)科大學(xué)
【學(xué)位級別】:博士
【學(xué)位授予年份】:2017
【分類號】:R687.3
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