基于Masquelet诱导膜技术比较不同固定方式构建的胫骨大段骨缺损模型
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摘要
目的基于Masquelet诱导膜技术,比较内固定钢板、髓内针和外固定架三种固定方式建立的大鼠胫骨大段骨缺损(MTBD)模型及诱导膜形成特点,从而选择较优的模型构建方法。方法 60只10周龄SPF级雄性SD大鼠随机分为3组:内固定钢板组(IFP)、髓内针组(IMP)和环形外固定架组(CEF)。在右侧胫骨中段构建4 mm骨缺损模型,分别应用自制六孔不锈钢钢板、直径1 mm克氏针、自制环形外固定架固定。记录造模用时、出血量及肢体肿胀持续时间;行X线检查,观察骨水泥、固定装置稳定情况;诱导膜行HE染色,观察组织形态结构特点。结果在造模用时、出血量及模型成功率方面,IMP和CEF两组明显优于IFP组(P<0.05)。②CEF组肿胀时间最短,但三组之间肿胀持续时间差异无显著性(P> 0.05)。③IFP组出现1例螺钉松动和3例骨水泥松动,CEF组出现1例骨水泥松动,而IMP组固定良好。④在感染方面,IFP组出现3例钢板外露,IMP组出现2例脓性包块,而CEF组无感染发生。⑤诱导膜组织厚度在460～520μm,三组差异无显著性(P> 0.05)。结论三种方式均可成功构建MTBD模型,但综合考虑CEF为模拟Masquelet技术构建大鼠MTBD模型较优的方式。
Objective To compare the characteristics of massive tibial bone defect(MTBD) models and induced membrane established by the internal fixation plate(IFP), intramedullary pin(IMP), and circular external fixator(CEF) based on Masquelet technology and selecting the optimal model method. Methods A total of 60 10-week-old SD male rats of SPF grade were randomly divided into three groups,namely, the IFP group, IMP group, and CEF group. A 4-mm bone defect model was generated at the middle of the right tibia, which was fixed with a custom-made six-hole stainless steel plate, a 1-mm-diameter Kirschner wire, and a custom-made circular external fixator, respectively. The time of modeling, the amount of bleeding, and the duration of limb swelling were recorded. X-ray examination was performed to observe the stability of bone cement and fixation devices. HE staining was conducted to observe the histomorphological characteristics. Results In terms of modeling time, bleeding volume, and model success rate, the IMP and CEF groups were significantly better than the IFP group, and significant differences were observed(P<0.05). The duration of limb swelling was the shortest in the CEF group, but no significant difference was found(P>0.05). In addition, one case of screw loosening and three cases of bone cement loosening occurred in the IFP group, and 1 case of cement loosening occurred in the CEF group, whereas bone cement was well fixed in the IMP group. With regard to infection, there were three cases of plate exposure in the IFP group, two cases of purulent mass in the IMP group, and no infection in the CEF group. The thickness of induced membrane in the three groups was 460-520 μm, showing no significant difference(P>0.05). Conclusions Taking the findings together, the three fixation models can successfully construct the MTBD model, but CEF is optimal for constructing the MTBD model by simulating the Masquelet technology.
Objective To compare the characteristics of massive tibial bone defect(MTBD) models and induced membrane established by the internal fixation plate(IFP), intramedullary pin(IMP), and circular external fixator(CEF) based on Masquelet technology and selecting the optimal model method. Methods A total of 60 10-week-old SD male rats of SPF grade were randomly divided into three groups,namely, the IFP group, IMP group, and CEF group. A 4-mm bone defect model was generated at the middle of the right tibia, which was fixed with a custom-made six-hole stainless steel plate, a 1-mm-diameter Kirschner wire, and a custom-made circular external fixator, respectively. The time of modeling, the amount of bleeding, and the duration of limb swelling were recorded. X-ray examination was performed to observe the stability of bone cement and fixation devices. HE staining was conducted to observe the histomorphological characteristics. Results In terms of modeling time, bleeding volume, and model success rate, the IMP and CEF groups were significantly better than the IFP group, and significant differences were observed(P<0.05). The duration of limb swelling was the shortest in the CEF group, but no significant difference was found(P>0.05). In addition, one case of screw loosening and three cases of bone cement loosening occurred in the IFP group, and 1 case of cement loosening occurred in the CEF group, whereas bone cement was well fixed in the IMP group. With regard to infection, there were three cases of plate exposure in the IFP group, two cases of purulent mass in the IMP group, and no infection in the CEF group. The thickness of induced membrane in the three groups was 460-520 μm, showing no significant difference(P>0.05). Conclusions Taking the findings together, the three fixation models can successfully construct the MTBD model, but CEF is optimal for constructing the MTBD model by simulating the Masquelet technology.
引文
[1] 金志超,蔡群斌,曾志奎,等. 诱导膜技术治疗大段骨损研究进展[J].中国骨伤,2018,31(05):488-492.Jin ZC,Cai QB,Zeng ZK,et al. Research progress on induced membrane technique for the treatment of segmental bone defect[J].Chin J Orthop Trauma,2018,31(05):488-492.
[2] 马云飞. 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[D].广州:南方医科大学,2017.Ma YF. Experimental study on repairing large segmental bone defects of SD rats by medical calcium sulfate mediated Masquelet technique[D]. Guangzhou: Southern Medical University,2017.
[3] Schmidmaier G,Moghaddam A. Long bone nonunion[J]. Z Orthop Unfall,2015,153(6):659-676.
[4] 赵文博,刘雷. 长骨大段骨缺损治疗方式的研究进展[J].现代临床医学,2014,40(03):230-232+237.Zhao WB,Liu L. Research progress in the treatment of large segmental bone defects of long bones[J].J Mord Clin Med,2014,40(03):230-232+237.
[5] 臧志海. Masquelet技术临床应用进展[J]. 继续医学教育,2018,32(06):78-80.Zang ZH. Progress in clinical application of Masquelet technology[J].Contin Med Educ,2018,32(06):78-80.
[6] 刘兵,周大鹏,刘欣伟,等. Masquelet技术治疗胫骨中段开放骨折合并骨缺损24例临床研究[J].创伤与急危重病医学,2017,5(05):262-266.Liu B,Zhou DP,Liu XW,et al. Masquelet technique for treatment of complex open fracture of tibial shaft with bone defects in 24 cases[J].Trauma Critl Care Med,2017,5(05):262-266.
[7] Morelli I,Drago L,George DA,et al. Masquelet technique: myth or reality? a systematic review and meta-analysis[J].Injury,2016,47(Suppl6):S68-S76.
[8] Wang XH,Wei FD,Luo F,et al.Induction of granulation tissue for the secretion of growth factors and the promotion of bone defect repair[J]. J Orthop Surg Res,2015,10:147.
[9] Henrich D,Seebach C,Nau C,et al. Establishment and characterization of the Masquelet induced membrane technique in a rat femur critical-sized defect model[J].J Tissue Eng Regen Med,2016,10(10):E382-E396.
[10] 吴琳,王禄增,哈斯达来,等.应力对大段骨缺损修复影响的实验兔模型探讨[J].中国实验动物学报,2011,19(01):26-28+99.Wu L,Wang LZ,Hasi DL,et al. Effect of stress on reconstruction of a large bone defect: establishment of an experimental rabbit model[J]. Acta Lab Anim Sci Sin,2011,19(01):26-28+99.
[11] 王文凯,曾昕,左睿,等. 小鼠股骨骨缺损诱导膜模型的构建与评估[J].第三军医大学学报,2018,40(09):805-809.Wang WK, Zeng X,Zuo R,et al. Establishment and evaluation of mouse model of induced membrane by femur bone defect[J]. Acta Acad Med Mil Tert,2018,40(09):805- 809.
[12] 王雷,王孝辉,张海龙,等. 不同剂量骨碎补总黄酮对大鼠Masquelet技术诱导膜中BMP-2和VEGF表达的影响[J].中国中医骨伤科志,2018,26(04):1-4.Wang L,Wang XH,Zhang HL,et al. Effects of different dose of rhizoma drynariae on expression of BMP-2 and VEGF in membrane of the rats induced by Masquelet technology [J].Chin J Trad Med Traum Orthop,2018,26(04):1-4.
[13] 刘鐘阳,陈新,苏佳灿.骨折实验动物模型研究进展[J].中国骨质疏松杂志,2010,16(10):791-793+780.Liu ZY,Chen X,Sun JC. Research progress in animal models of bone fracture[J].Chin J Osteoporos,2010,16(10):791-793+780.
[14] Haines NM,Lack WD,Seymour RB, et al. Defining the lower limit of a “critical bone defect” in open diaphyseal tibial fractures[J]. J Orthop Trauma,2016,30(5):e158-63
[15] DeCoster TA,Gehlert RJ,Mikola EA, et al. Management of posttraumatic segmental bone defects[J]. J Am Acad Orthop Surg,2004,12(1):28-38.
[16] Clements JR,Carpenter BB,Pourciau JK. Treating segmental bone defects: a new technique[J]. J Foot Ankle Surg,2008,47(4):350-356.
[17] 关德强,于波. 大段骨缺损修复的研究进展[J].世界最新医学信息文摘,2017,17 (52): 70-71+76.Guan DQ,Yue B. Research progress on repair of large segmental bone defects [J]. World Latest Med Inf,2017,17(52):70-71+76.
[18] Masquelet AC,Fitoussi F,Begue T,et al. Reconstruction of the long bones by the induced membrane and spongy autograft[J]. Ann Chir Plast Esthet,2000,45(3):346-353.
[19] Masquelet AC. Muscle reconstruction in reconstructive surgery:soft tissue repair and long bone reconstruction[J].Langenbecks Arch Surg,2003,388(5): 344-346.
[20] Masquelet AC,Begue T. The concept of induced membrane for reconstruction of long bone defects[J]. Orthop Clin North Am,2010,41(1):27-37.
[21] Masquelet AC,Obert L. Induced membrane technique for bone defects in the hand and wrist[J]. Chir Main,2010,29 Suppl 1:S221-224.
[22] Seholz AO,Gehrmann S,Glombitza M,et al. Reconstruction of septic diaphyseal bone defects with the induced membrane technique[J].Injury,2015,46(Suppl 4):S121-S124.
[23] Azi ML,Teixeira AA,Cotias RB,et al.Membrane induced osteogenesis in the management of posttraumatic bone defects[J].J Orthop Trauma,2016,30(10):545-550.
[24] 邱旭升,陈一心,戚晓阳,等.诱导膜技术治疗感染性骨缺损的疗效分析[J].中国修复重建外科杂志,2017,31(09):1064-1068.Qiu XS,Chen YX,Qi XY,et al. Effectiveness analysis of induced membrane technique in the treatment of infectious bone defect[J].Chin J Repar Reconst Surg,2017,31(09):1064-1068.
[25] 范少地,刘志恒,胡万华,等.病变切除外固定支架固定及膜诱导技术治疗胫骨骨折术后骨髓炎[J].中国骨伤,2017,30(4):372-376.Fan SD,Liu ZH,Hu WH,et al. Excision of necrotic and infected tissues combined with induced membrane and external fixator technique for the treatment of chronic osteomyelitis in tibia after fracture operation [J].Chin J Orthop Trauma,2017,30 (4):372-376.
[26] Wang X,Luo F,Huang K,et al. Induced membrane technique for the treatment of bone defects due to post-traumatic osteomyelitis[J]. Bone Joint Res,2016,5 (3):101-105.
[27] Chotel F,Nguiabanda L,Braillon P,et al. Induced membrane technique for reconstruction after bone tumor resection in children: a preliminary study[J]. Orthop Traumatol Surg Res,2012,98(3):301-308.
[28] Accadbled F,Mazeau P,Chotel F,et al. Induced-membrane femur reconstruction after resection of bone malignancies: three cases of massive graft resorption in children[J]. Orthop Traumatol Surg Res,2013,99(4):479-483.
[29] 戚晓阳,邱旭升,施鸿飞,等.大段骨缺损的治疗进展[J].实用骨科杂志,2017,23(08):715-719.Qi XY,Qiu XS,Shi HF,et al. Progress in the treatment of large segmental bone defects[J]. J Pract Orthop,2017,23(08):715-719.
[30] 李顺东,许超,童培建. 外固定支架结合损伤控制理念治疗四肢开放性骨病例对照研究[J].中国骨伤,2015,28(02):130-135.Li SD,Xu C,Dong PJ. Application of external fixator combined with damage control treatment for open fracture of the extremities[J]. Chin J Orthop Trauma,2015,28(02):130-135.
[31] 计忠伟,包倪荣,赵建宁,等. 人工全膝关节置换术后疼痛原因分析[J].中国骨伤,2014,27(11):970-974.Ji ZW,Bao NR,Zhao JN,et al.Cause analysis of postoperative pain after total knee arthroplasty[J].Chin J Orthop Trauma,2014,27(11):970-974.
[32] 朱晨,孔荣,方诗元,等. 人工关节假体周围感染与无菌性松动界膜组织中人β-防御素3的表达差异分析[J].生物骨科材料与临床研究,2016,13(02):12-16+82.Zhu C,Kong R,Fang SY,et al.Analysis the expression of human β-defensin-3 in human interfacial membranes around periprosthetic joint infection compared with aseptic loosening[J]. Orthop Biomed Materi Clin Study,2016,13(02):12-16+82.
[33] 王坤正. 锥部磨损与全髋关节置换术后无菌性松动的关系[J].医学研究生学报,2018,31(04):344-349.Wang KZ. Corrosion at the head-neck taper as a cause for aspetic loosening after total arthroplasty[J]. J Med Postgra,2018,31(04):344-349.
[34] 赵震宇,邵林,刘建宇,等. 外固定方法制作的大鼠股骨骨折模型[J].中国组织工程研究与临床康复,2011,15(24):4387-4390.Zhao ZY,Shao L,Liu JY,et al. Preparation of rat femoral fracture model with an external fixator[J]. J Clin Rehabil Tis Eng Res,2011,15(24):4387-4390.
[35] Pélissier P,Lefevre Y,Delmond S,et al. Influences of induced membranes on heterotopic bone formation within an osteo-inductive complex experimental study in rabbits[J].Ann Chir Plast Esthet,2009,54(1):16-20.
[2] 马云飞. 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[D].广州:南方医科大学,2017.Ma YF. Experimental study on repairing large segmental bone defects of SD rats by medical calcium sulfate mediated Masquelet technique[D]. Guangzhou: Southern Medical University,2017.
[3] Schmidmaier G,Moghaddam A. Long bone nonunion[J]. Z Orthop Unfall,2015,153(6):659-676.
[4] 赵文博,刘雷. 长骨大段骨缺损治疗方式的研究进展[J].现代临床医学,2014,40(03):230-232+237.Zhao WB,Liu L. Research progress in the treatment of large segmental bone defects of long bones[J].J Mord Clin Med,2014,40(03):230-232+237.
[5] 臧志海. Masquelet技术临床应用进展[J]. 继续医学教育,2018,32(06):78-80.Zang ZH. Progress in clinical application of Masquelet technology[J].Contin Med Educ,2018,32(06):78-80.
[6] 刘兵,周大鹏,刘欣伟,等. Masquelet技术治疗胫骨中段开放骨折合并骨缺损24例临床研究[J].创伤与急危重病医学,2017,5(05):262-266.Liu B,Zhou DP,Liu XW,et al. Masquelet technique for treatment of complex open fracture of tibial shaft with bone defects in 24 cases[J].Trauma Critl Care Med,2017,5(05):262-266.
[7] Morelli I,Drago L,George DA,et al. Masquelet technique: myth or reality? a systematic review and meta-analysis[J].Injury,2016,47(Suppl6):S68-S76.
[8] Wang XH,Wei FD,Luo F,et al.Induction of granulation tissue for the secretion of growth factors and the promotion of bone defect repair[J]. J Orthop Surg Res,2015,10:147.
[9] Henrich D,Seebach C,Nau C,et al. Establishment and characterization of the Masquelet induced membrane technique in a rat femur critical-sized defect model[J].J Tissue Eng Regen Med,2016,10(10):E382-E396.
[10] 吴琳,王禄增,哈斯达来,等.应力对大段骨缺损修复影响的实验兔模型探讨[J].中国实验动物学报,2011,19(01):26-28+99.Wu L,Wang LZ,Hasi DL,et al. Effect of stress on reconstruction of a large bone defect: establishment of an experimental rabbit model[J]. Acta Lab Anim Sci Sin,2011,19(01):26-28+99.
[11] 王文凯,曾昕,左睿,等. 小鼠股骨骨缺损诱导膜模型的构建与评估[J].第三军医大学学报,2018,40(09):805-809.Wang WK, Zeng X,Zuo R,et al. Establishment and evaluation of mouse model of induced membrane by femur bone defect[J]. Acta Acad Med Mil Tert,2018,40(09):805- 809.
[12] 王雷,王孝辉,张海龙,等. 不同剂量骨碎补总黄酮对大鼠Masquelet技术诱导膜中BMP-2和VEGF表达的影响[J].中国中医骨伤科志,2018,26(04):1-4.Wang L,Wang XH,Zhang HL,et al. Effects of different dose of rhizoma drynariae on expression of BMP-2 and VEGF in membrane of the rats induced by Masquelet technology [J].Chin J Trad Med Traum Orthop,2018,26(04):1-4.
[13] 刘鐘阳,陈新,苏佳灿.骨折实验动物模型研究进展[J].中国骨质疏松杂志,2010,16(10):791-793+780.Liu ZY,Chen X,Sun JC. Research progress in animal models of bone fracture[J].Chin J Osteoporos,2010,16(10):791-793+780.
[14] Haines NM,Lack WD,Seymour RB, et al. Defining the lower limit of a “critical bone defect” in open diaphyseal tibial fractures[J]. J Orthop Trauma,2016,30(5):e158-63
[15] DeCoster TA,Gehlert RJ,Mikola EA, et al. Management of posttraumatic segmental bone defects[J]. J Am Acad Orthop Surg,2004,12(1):28-38.
[16] Clements JR,Carpenter BB,Pourciau JK. Treating segmental bone defects: a new technique[J]. J Foot Ankle Surg,2008,47(4):350-356.
[17] 关德强,于波. 大段骨缺损修复的研究进展[J].世界最新医学信息文摘,2017,17 (52): 70-71+76.Guan DQ,Yue B. Research progress on repair of large segmental bone defects [J]. World Latest Med Inf,2017,17(52):70-71+76.
[18] Masquelet AC,Fitoussi F,Begue T,et al. Reconstruction of the long bones by the induced membrane and spongy autograft[J]. Ann Chir Plast Esthet,2000,45(3):346-353.
[19] Masquelet AC. Muscle reconstruction in reconstructive surgery:soft tissue repair and long bone reconstruction[J].Langenbecks Arch Surg,2003,388(5): 344-346.
[20] Masquelet AC,Begue T. The concept of induced membrane for reconstruction of long bone defects[J]. Orthop Clin North Am,2010,41(1):27-37.
[21] Masquelet AC,Obert L. Induced membrane technique for bone defects in the hand and wrist[J]. Chir Main,2010,29 Suppl 1:S221-224.
[22] Seholz AO,Gehrmann S,Glombitza M,et al. Reconstruction of septic diaphyseal bone defects with the induced membrane technique[J].Injury,2015,46(Suppl 4):S121-S124.
[23] Azi ML,Teixeira AA,Cotias RB,et al.Membrane induced osteogenesis in the management of posttraumatic bone defects[J].J Orthop Trauma,2016,30(10):545-550.
[24] 邱旭升,陈一心,戚晓阳,等.诱导膜技术治疗感染性骨缺损的疗效分析[J].中国修复重建外科杂志,2017,31(09):1064-1068.Qiu XS,Chen YX,Qi XY,et al. Effectiveness analysis of induced membrane technique in the treatment of infectious bone defect[J].Chin J Repar Reconst Surg,2017,31(09):1064-1068.
[25] 范少地,刘志恒,胡万华,等.病变切除外固定支架固定及膜诱导技术治疗胫骨骨折术后骨髓炎[J].中国骨伤,2017,30(4):372-376.Fan SD,Liu ZH,Hu WH,et al. Excision of necrotic and infected tissues combined with induced membrane and external fixator technique for the treatment of chronic osteomyelitis in tibia after fracture operation [J].Chin J Orthop Trauma,2017,30 (4):372-376.
[26] Wang X,Luo F,Huang K,et al. Induced membrane technique for the treatment of bone defects due to post-traumatic osteomyelitis[J]. Bone Joint Res,2016,5 (3):101-105.
[27] Chotel F,Nguiabanda L,Braillon P,et al. Induced membrane technique for reconstruction after bone tumor resection in children: a preliminary study[J]. Orthop Traumatol Surg Res,2012,98(3):301-308.
[28] Accadbled F,Mazeau P,Chotel F,et al. Induced-membrane femur reconstruction after resection of bone malignancies: three cases of massive graft resorption in children[J]. Orthop Traumatol Surg Res,2013,99(4):479-483.
[29] 戚晓阳,邱旭升,施鸿飞,等.大段骨缺损的治疗进展[J].实用骨科杂志,2017,23(08):715-719.Qi XY,Qiu XS,Shi HF,et al. Progress in the treatment of large segmental bone defects[J]. J Pract Orthop,2017,23(08):715-719.
[30] 李顺东,许超,童培建. 外固定支架结合损伤控制理念治疗四肢开放性骨病例对照研究[J].中国骨伤,2015,28(02):130-135.Li SD,Xu C,Dong PJ. Application of external fixator combined with damage control treatment for open fracture of the extremities[J]. Chin J Orthop Trauma,2015,28(02):130-135.
[31] 计忠伟,包倪荣,赵建宁,等. 人工全膝关节置换术后疼痛原因分析[J].中国骨伤,2014,27(11):970-974.Ji ZW,Bao NR,Zhao JN,et al.Cause analysis of postoperative pain after total knee arthroplasty[J].Chin J Orthop Trauma,2014,27(11):970-974.
[32] 朱晨,孔荣,方诗元,等. 人工关节假体周围感染与无菌性松动界膜组织中人β-防御素3的表达差异分析[J].生物骨科材料与临床研究,2016,13(02):12-16+82.Zhu C,Kong R,Fang SY,et al.Analysis the expression of human β-defensin-3 in human interfacial membranes around periprosthetic joint infection compared with aseptic loosening[J]. Orthop Biomed Materi Clin Study,2016,13(02):12-16+82.
[33] 王坤正. 锥部磨损与全髋关节置换术后无菌性松动的关系[J].医学研究生学报,2018,31(04):344-349.Wang KZ. Corrosion at the head-neck taper as a cause for aspetic loosening after total arthroplasty[J]. J Med Postgra,2018,31(04):344-349.
[34] 赵震宇,邵林,刘建宇,等. 外固定方法制作的大鼠股骨骨折模型[J].中国组织工程研究与临床康复,2011,15(24):4387-4390.Zhao ZY,Shao L,Liu JY,et al. Preparation of rat femoral fracture model with an external fixator[J]. J Clin Rehabil Tis Eng Res,2011,15(24):4387-4390.
[35] Pélissier P,Lefevre Y,Delmond S,et al. Influences of induced membranes on heterotopic bone formation within an osteo-inductive complex experimental study in rabbits[J].Ann Chir Plast Esthet,2009,54(1):16-20.