超顺磁性支架材料修复兔下颌骨缺损的实验研究

Experimental study of superparamagentic scaffolds used to repair rabbit mandibular defect

目的超顺磁性材料在骨组织工程中的研究较少。文中旨在探讨超顺磁性支架材料聚乳酸-羟基乙酸(PLGA)/含铁的羟基磷灰石颗粒(Fe-HA)修复兔下颌骨缺损的成骨效能并评估材料的生物相容性。方法随机选取新西兰大白兔36只,采用随机数字表法分为6组:分别为术后非静磁场饲养条件下的非静磁场对照组(不植入材料),非静磁场PLGA组(植入PLGA膜材料)、非静磁场PLGA/Fe-HA组(植入PLGA/Fe-HA材料),静磁场饲养条件下的静磁场对照组(不植入材料)、静磁场PLGA组(植入PLGA膜材料)、静磁场PLGA/Fe-HA组(植入PLGA/Fe-HA材料),每组6只。制备双侧下颌骨缺损模型,分别于术后4、12周处死实验动物,标记并制备颌骨标本,进行大体观察、Micro CT扫描、HE染色,并对缺损区骨密度值结果进行分析。12周术后实验兔进行血液学检测、肝肾组织进行病理检验。结果非静磁场PLGA/Fe-HA组、静磁场PLGA/Fe-HA组4周时开始出现缺损区边缘粗糙,缺损直径减小,新生骨形成表现;12周时缺损区形成光滑、连续的骨修复。非静磁场PLGA组、静磁场PLGA组12周时表现为粗糙、不整齐的骨痂修复,缺损边缘与正常骨组织边界可见,非静磁场对照组、静磁场对照组缺损中心区域仍有部分骨缺损未修复。12周时与静磁场PLGA/Fe-HA组骨密度值[(572.50±19.09)mg HA/cm3]比较,静磁场PLGA组[(467.00±6.24)mg HA/cm3]、静磁场对照组[(480.67±2.08)mg HA/cm3]、非静磁场PLGA/Fe-HA组[(461.00±19.79)mg HA/cm3]、非静磁场PLGA组[(446.00±11.31)mg HA/cm3]及非静磁场对照组[(422.00±28.28)mg HA/cm3]均明显降低(P<0.05)。静磁场PLGA/Fe-HA组4周时骨密度值[(572.50±19.09)mg HA/cm3]较12周的[(276.00±28.28)mg HA/cm3]明显增加(P<0.05),其他各组4周与12周组内比较差异均有统计学意义(P<0.05)。结论 PLGA/Fe-HA超顺磁性支架材料可促进骨缺损修复,在磁场作用下材料的成骨效能被优化,生物相容性尚可。

Objective Sperparamagnetic material is widely used in tumor localization and treatment , but there are still few studies in bone tissue engineering. This study aims to investigate the osteogenic efficiency of superparamagnetic scaffolds poly lactic acid hydroxy acetic acid （ PLGA）/iron-doped hydroxyapatite （Fe-HA） for repairing rabbit mandibular defects, as well as evaluating the biocompatibility of the material. Methods 36 New Zealand rabbits were randomly selected and randomly divided into 6 groups, control without and with static magnetic field （ SMF） groups （ no material is implanted）,PLGA scaffold without and with SMF groups （ implanted PLGA）, PLGA/Fe-HA scaffold without and with SMF groups （ implanted PLGA/Fe-HA） , each group has 6 rabbits. We created bilateral mandibular defect models, executed the rabbits at 4 weeks and 12 weeks post-surgery, marked the mandibular specimens which detected by general observation, Micro-CT and HE staining, and analyzed the results of bone mineral density in defect area. The hematological detection, pathological examination of liver and kidney samples were carried out at 12 weeks pot-surgery. . Results The PLGA/Fe-HA scaffold without and with SMF groups began to appear rough defect area edge, decreased defect diameter, new bone formation from 4 weeks; the defect area formed a smooth, continuous bone repair from 12 weeks. The PLGA scaffold without and with SMF groups appeared rough, irregular callus repair, visible boundary between defect edge and normal bone tissue. There are still have part of unrepaired bone defect in the center of defect area in the control without and with SMF groups. At 12 weeks,the bone mineral density of PLGA/Fe-HA scaffold with SMF group [ （572.50± 19.09） mgHA/cm^3] ,respectively,compared with the PLGA scaffold with SMF group [ （467.00±6.24） mgHA/cm^3 ],the control with SMF scaffoldgroup [（480.00±2.08） mgHA/cm^3] ,thePLGA/Fe-HA scaffold without SMFgroup [ （4 6 1 .00±19.79）mgHA/cm^3] ,thePL- GA scaffold without SMF group [ （ 446.00± 11.31） mgHA/cm^3 ] and the control without SMF group [ （ 422.00±28.28 ） mgHA/cm^3], all the differences were statistically significant （P〈0.05）. The bone mineral density of PLGA/Fe-HA scaffold with SMF group at 4 weeks [ （ 572.50± 19.09） mgHA/cm^3 ] was significantly higher than that at 12 weeks [ （ 276.00±28.28 ） mgHA/cm^3 ] （P〈0.05） , the differences between 4 weeks and 12 weeks in other groups were statistically significant （P〈0.05）. Conclusion The superparamagentic PLGA/Fe-HA scaffolds can promote the repair of bone defect , optimize the osteogenic effect of the material with SMF. Also ,the scaffold showed a good biocompatibility.