自体微小颗粒骨载万古霉素复式微球治疗兔骨感染性骨缺损的实验研究
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摘要
目的检验兔自体微小颗粒骨载万古霉素PLGA/CS复式微球体内抗感染性及骨修复活性。方法按Mader J.T的骨髓炎造模方法造成双侧桡骨中上段骨髓炎模型兔48只;在植入实验前彻底清创,并造成双侧桡骨中上段1.5cm的骨缺损,将造模成功的兔随机分为3组,每组16只,A、B、C各组分别植入自体微小颗粒骨、自体微小颗粒骨与万古霉素、自体微小颗粒骨与载万古霉素复式微球后,在第2、4、8和12周四个时间点每组各取4只兔处死行延长区大体观察,X线正侧位片观察;同时在骨延长区取骨组织做组织学切片,HE染色观察新骨生成情况。结果影像学X线评分和组织学评分见,第2、4和8周时C组新骨形成均优于A、B组(P<0.05)。B组第2、4、8周新生骨形成优于A组(P<0.05);术后第12周影像学X线评分A、B、C三组分值差异均无统计学意义(P>0.05),术后第12周组织学评分B、C组成骨优于A组(P<0.05),B、C组比较差异无统计学意义(P>0.05)。结论载万古霉素复式微球与自体微小颗粒骨混合对兔感染性骨缺损的修复具有比较显著的促进作用,可以加快骨缺损成骨过程的新骨生成。
Objective To investigate the anti-infectivity and bone repair activity of autologous micro-particles loaded with vancomycin PLGA/CS double microspheres. Methods The rabbit osteomyelitis model in bilateral radial bone of 48 rabbits were established by Mader JT osteomyelitis modeling method.Debridement performed before implantation experiments and caused bilateral radial bone defects of the upper section of 1.5cm. 48 successful modeling rabbits were randomly divided into three groups: group A with tiny particles of autologous bone implants,group B with autogenous micro grain bone implant with vancomycin and group C with autogenous micro grain bone double vancomycin microspheres implantation,Four rabbits in each group were sacrificed at 2~(nd) week,4~(th) week,8~(th) week,12~(th) week and the extension area was observed.X-ray film of bones was observed too and bones was taken from the bone extension area. Histological sections were made and the new bone formation was observed by HE staining. Results Radiographic scoring showed that the new bone formation of group C at 2nd week,4thweek and 8~(th) week was better significantly than that of group A and group B at the same time(P<0.05). The bone formation of group B was better significantly than that of group A at 2~(nd) week,4~(th) week and 8thweek(P<0.05). There were no significant difference in radiographic scores among group A,B and C at 12~(th) week after operation(P>0.05). Histological scoring of group B and group C was better significantly than that of group A at 12~(th) week(P<0.05). Conclusion The combination of vancomycin microspheres and autogenous microgranular bone could promote the recovery of the bone defects in rabbits,and could accelerate the formation of new bone during osteogenesis.
Objective To investigate the anti-infectivity and bone repair activity of autologous micro-particles loaded with vancomycin PLGA/CS double microspheres. Methods The rabbit osteomyelitis model in bilateral radial bone of 48 rabbits were established by Mader JT osteomyelitis modeling method.Debridement performed before implantation experiments and caused bilateral radial bone defects of the upper section of 1.5cm. 48 successful modeling rabbits were randomly divided into three groups: group A with tiny particles of autologous bone implants,group B with autogenous micro grain bone implant with vancomycin and group C with autogenous micro grain bone double vancomycin microspheres implantation,Four rabbits in each group were sacrificed at 2~(nd) week,4~(th) week,8~(th) week,12~(th) week and the extension area was observed.X-ray film of bones was observed too and bones was taken from the bone extension area. Histological sections were made and the new bone formation was observed by HE staining. Results Radiographic scoring showed that the new bone formation of group C at 2nd week,4thweek and 8~(th) week was better significantly than that of group A and group B at the same time(P<0.05). The bone formation of group B was better significantly than that of group A at 2~(nd) week,4~(th) week and 8thweek(P<0.05). There were no significant difference in radiographic scores among group A,B and C at 12~(th) week after operation(P>0.05). Histological scoring of group B and group C was better significantly than that of group A at 12~(th) week(P<0.05). Conclusion The combination of vancomycin microspheres and autogenous microgranular bone could promote the recovery of the bone defects in rabbits,and could accelerate the formation of new bone during osteogenesis.
引文
[1]Hatzenbuehler J,Pulling TJ.Diagnosis and management of osteo myelitis[J].Am Fam Physician,2011,84(9):1027-1033.
[2]Popat KC,Eltgroth M,Latempa TJ,et al.Decreased Staphylococcus epidermis adhesion and increased osteoblast functionality on antibiotic-loaded titania nanotubes[J].Biomaterials,2007,28(32):4880-4888.
[3]朱磊,王志斌,李飞,等.载盐酸万古霉素PLGA/CS缓释微球的制备及研究[J].内蒙古医学杂志,2015,47(6):641-645.
[4]王明波,冯庆玲.乳酸-乙醇酸共聚物/壳聚糖复式微球缓释蛋白[J].复合材料学报,2011,28(5):20-26.
[5]Chang KY,Cheng LW,Ho GH,et al.Fabrication and characterization of poly(gamma-glutamic acid)-graftchondroitin sulfate/polycaprolactone porous scaffolds for cartilage tissue engineering[J].Acta Biomater,2009,5(6):1937-1947.
[6]孟毅,羊庚生,王向阳,等.不同致伤原因重症胸外伤的临床特点及救治[J].创伤外科杂志,2004,6(1):16-18.
[7]李志远,李刚,荆浩,等.自体微小颗粒骨一期治疗感染性骨缺损及骨不连的临床研究[J].宁夏医科大学学报,2012,34(4):385-387.
[8]李亮,杨海波,米占虎,等.自体微小颗粒骨复合纳米人工骨修复材料治疗感染性骨缺损的疗效分析[J].宁夏医学杂志,2015,37(1):63-65.
[9]李刚,李志远,荆浩,等.自体微小颗粒骨复合骨髓间充质干细胞治疗兔感染性骨缺损的实验研究[J].宁夏医科大学学报,2012,34(5):462-465.
[10]南宠,荆浩,周岳,等.自体微小颗粒骨植骨混合万古霉素开放性植骨修复感染性胫骨缺损[J].中国组织工程研究,2013,17(25):4585-4592.
[11]葛茶娜,黎飞猛,林周胜,等.抗生素缓释系统载体在慢性骨髓炎治疗中的应用研究进展[J].成都医学院学报,2016,11(1):134-137.
[12]Allison SD.Analysis of initial burst in PLGA microparticles[J].Expert Opin Drug Deliv,2008,5(6):615-628.
[13]吴玉彬,韩相恩.聚(乳酸-羟基乙酸)共聚物PLGA缓释微球的制备及其缓释性能研究[J].甘肃石油和化工,2009(2):29-34.
[14]何源龙,郑欣,陈一心.抗感染材料应用于慢性骨髓炎治疗的研究进展[J].中国矫形外科杂志,2014,22(5):426-429.
[15]Wang M,Feng Q,Guo X,et al.A dual microsphere based on PLGA and chitosan for delivering the oligopeptide derived from BMP-2[J].Polymer Degradation and Stability,2011,96(1):107-113.
[16]Wang X,Kim HJ,Xu P,et al.Biomaterial coatings by stepwise deposition of silk fibroin[J].Langmuir,2005,21(24):11335-11341.
[17]侯占江,闫景龙,付海亮,等.微小颗粒骨异位成骨过程中碱性成纤维细胞生长因子的表达[J].中华创伤杂志,2003,19(12):734-737.
[2]Popat KC,Eltgroth M,Latempa TJ,et al.Decreased Staphylococcus epidermis adhesion and increased osteoblast functionality on antibiotic-loaded titania nanotubes[J].Biomaterials,2007,28(32):4880-4888.
[3]朱磊,王志斌,李飞,等.载盐酸万古霉素PLGA/CS缓释微球的制备及研究[J].内蒙古医学杂志,2015,47(6):641-645.
[4]王明波,冯庆玲.乳酸-乙醇酸共聚物/壳聚糖复式微球缓释蛋白[J].复合材料学报,2011,28(5):20-26.
[5]Chang KY,Cheng LW,Ho GH,et al.Fabrication and characterization of poly(gamma-glutamic acid)-graftchondroitin sulfate/polycaprolactone porous scaffolds for cartilage tissue engineering[J].Acta Biomater,2009,5(6):1937-1947.
[6]孟毅,羊庚生,王向阳,等.不同致伤原因重症胸外伤的临床特点及救治[J].创伤外科杂志,2004,6(1):16-18.
[7]李志远,李刚,荆浩,等.自体微小颗粒骨一期治疗感染性骨缺损及骨不连的临床研究[J].宁夏医科大学学报,2012,34(4):385-387.
[8]李亮,杨海波,米占虎,等.自体微小颗粒骨复合纳米人工骨修复材料治疗感染性骨缺损的疗效分析[J].宁夏医学杂志,2015,37(1):63-65.
[9]李刚,李志远,荆浩,等.自体微小颗粒骨复合骨髓间充质干细胞治疗兔感染性骨缺损的实验研究[J].宁夏医科大学学报,2012,34(5):462-465.
[10]南宠,荆浩,周岳,等.自体微小颗粒骨植骨混合万古霉素开放性植骨修复感染性胫骨缺损[J].中国组织工程研究,2013,17(25):4585-4592.
[11]葛茶娜,黎飞猛,林周胜,等.抗生素缓释系统载体在慢性骨髓炎治疗中的应用研究进展[J].成都医学院学报,2016,11(1):134-137.
[12]Allison SD.Analysis of initial burst in PLGA microparticles[J].Expert Opin Drug Deliv,2008,5(6):615-628.
[13]吴玉彬,韩相恩.聚(乳酸-羟基乙酸)共聚物PLGA缓释微球的制备及其缓释性能研究[J].甘肃石油和化工,2009(2):29-34.
[14]何源龙,郑欣,陈一心.抗感染材料应用于慢性骨髓炎治疗的研究进展[J].中国矫形外科杂志,2014,22(5):426-429.
[15]Wang M,Feng Q,Guo X,et al.A dual microsphere based on PLGA and chitosan for delivering the oligopeptide derived from BMP-2[J].Polymer Degradation and Stability,2011,96(1):107-113.
[16]Wang X,Kim HJ,Xu P,et al.Biomaterial coatings by stepwise deposition of silk fibroin[J].Langmuir,2005,21(24):11335-11341.
[17]侯占江,闫景龙,付海亮,等.微小颗粒骨异位成骨过程中碱性成纤维细胞生长因子的表达[J].中华创伤杂志,2003,19(12):734-737.