超顺磁性壳聚糖质粒明胶控释微球促进人工骨内新生血管的实验研究  

Superparamagnetic chitosan plasmids gelatin controlled release microspheres promote vascularization in artificial bone

作　　者：惠慧[1] 罗聪[1] 安洪[1] 蒋电明[1] 李明[1] 李廷玉[1] 张鑫[1] 岑超德 何大维[1] 

机构地区：[1]重庆医科大学附属儿童医院儿科研究所干细胞实验室,儿童发育疾病研究教育部重点实验室,儿科学重庆市重点实验室,重庆市儿童发育重大疾病诊治与预防国际科技合作基地,重庆医科大学附属儿童医院,400014

出　　处：《中华小儿外科杂志》2014年第5期323-328,共6页Chinese Journal of Pediatric Surgery

基　　金：重庆市科委自然科学基金计划资助项目（CSTC2011ggB1004）;重庆市卫生局医学科学技术研究项目（渝卫科教[2012]33号-2-113）;重庆市卫生局医学科学技术研究项目（渝卫科教E2010351号-2-197）

摘　　要：目的 提出并利用人工骨支架内部的磁性微动、营养物质交换原理,解决大段骨缺损人工骨内部血管化的问题.方法 取48只成年新西兰兔按数字随机表法随机分成4组,手术制成96侧桡骨骨缺损模型.A组：超顺磁性壳聚糖质粒明胶微球（SPCPGM＋静磁场＋振荡磁场）;B组：超顺磁性壳聚糖质粒明胶微球（SPCPGM＋静磁场）;C组：超顺磁性壳聚糖质粒明胶微球（SPCPGM）;D组：对照组,壳聚糖质粒明胶微球（CPGM）;通过大体观察、墨汁灌注、HE染色、免疫组化等评价其血管化效果.结果 纳米Fe3O4微粒呈球形,外形规则且表面光滑,粒径主要分布于50 nm左右,当氮磷比（N/P）达1∶0.6时,SPFCN能与质粒完全结合;A组新生组织出现最早,4～6周即形成成熟的血管网,且数量明显多于其他处理组,同时期残留的微球少于其他组;B组成血管过程与A组相似,成血管的时间迟于A组约两周左右;C、D组成血管时间晚于B组,同时期残留未降解的微球相对较多.结论 Fe3O微粒为超顺磁性纳米粒,且能够有效地与质粒结合;超顺磁性质粒（pDsVEGF165Red1-N1）壳聚糖明胶微球具有促进生物活性人工骨成血管的作用;静磁场和振动磁场联合应用,能够明显提高超顺磁性质粒壳聚糖明胶微球局部成血管作用;振荡磁场能够有效地减少局部磁性微球的残留.Objective To resolve the problem of vascularization in artificial bone for long bone defect in accordance with the theories of magnetic micro-movement and nutrient exchange.Methods A total of 48 adult New Zealand white rabbits were randomly divided into 4 groups of A：SPCPGM＋ static magnetic field ＋ oscillating magnetic field,B：SPCPGM ＋ static magnetic field,C：SPCPGM and D：CPGM.The bone defects in bilateral radii were substituted with cylinder porosity cages containing different microspheres.Then the bone defect specimens were obtained at weeks 2,4 and 6 post-operation.General observations and histological examinations were performed to evaluate the feasibility of repairing bone defects in different groups.Results Chitosan Fe3 O4 nanospheres had complete,smooth and round or oval shape.The diameter of Fe3O4 nanosphere was around 50 nm.And the complete binding of SPFCN with plasmid DNA was at the ratio of 1/0.6 （N/P）.Group A：forming mature vascular network in 4-6 weeks and the number of vessels was significantly more than the other treatment groups,remaining microspheres was less than the other groups at the same time; Group B..similar to group A but it was about two weeks later than group A; Groups C ＆amp; D..time of forming vessels was later than Group B and remaining microspheres were more than other groups.Conclusions The superparamagnetism nanoparticles Fe3O4 may effectively conjugate with plasmid.Super paramagnetic plasmid （pDsVEGF165Red1-N1） chitosan gelatin microspheres promote vascularization in artificial bones.A combination of static and oscillating magnetic fields significantly improves super paramagnetic plasmid （pDsVEGF165Red1-N1） chitosan gelatin microspheres in vascularization.Oscillating magnetic field can effectively reduce the local residual number of magnetic microspheres.

关 键 词：人工骨 转染 明胶 微球体 

分 类 号：R68[医药卫生—骨科学]