纳米级二氧化锆增韧羟基磷灰石的生物相容性

Biocompatibility for nano-zirconium dioxide-toughened hydroxyapatite

背景:作者前期实验观察了纳米级二氧化锆增韧的羟基磷灰石(ZrO2-HA)对兔骨髓基质干细胞的增殖、分化的影响。目的:评价自行研制的纳米级二氧化锆增韧的羟基磷灰石生物复合陶瓷的生物相容性。方法:实验根据卫生部的有关标准,采用纳米级二氧化锆增韧的羟基磷灰石材料对新西兰大白兔、健康成年昆明小鼠、成年大白鼠进行了急性毒性实验、亚急性毒性实验、热原实验、溶血实验及肌肉内植入实验。结果与结论:急性毒性试验结果:所有受试实验动物均没有死亡,实验前后体质量差异无显著性差异意义(P>0.05)。热原实验结果:没有致热作用。溶血实验:受试标本在1h之后大体观察判断均无明显溶血现象,酶标仪检测溶血度测得溶血率均小于5%。肌肉内植入实验:伤口均无感染发生,也未见材料排出。4周后,肌肉组织和材料结合紧密,材料孔隙里面有一定量的组织长入,周围肌肉组织始终保持正常形态结构。亚急性毒性试验:2周后复查体质量和血常规,与实验前的数据做比较差异无显著性意义。心,肝,肾组织苏木精-伊红染色光学显微镜观察没有发现坏死灶或其他病变。结果提示纳米级二氧化锆增韧的羟基磷灰石材料是一种无毒、无溶血性、不含热原物质的生物医用材料,对肌肉无刺激作用,在兔体内没有发生炎性排斥反应,与肌肉结合牢固,具有良好的生物相容性。对于将来骨缺损的修复,可能可以作为假体替代材料试用于临床,但还需要全面的评估。

BACKGROUND：Previous research has investigated the effect of nano-zirconium dioxide-toughened hydroxyapatite（nano-ZrO2-HA）on the proliferation and differentiation of rabbit bone marrow stromal cells.OBJECTIVE：To evaluate the biocompatibility of nano-ZrO2-HA compound.METHODS：The experiments of acute toxicity,subacute toxicity,pyrogen,hemolysis,and intramuscular implantation were performed on New Zealand rabbits,healthy adult Kunming mice,and adult rats according to＂Technical Evaluation Standards of Biomedical Materials and Medical Instruments＂,promulgated by Chinese Board of Health.RESULTS AND CONCLUSION：Acute toxicity：All experimental animals survived.There was no significant difference in body mass before and after testing（P0.05）.Pyrogen：Heating reaction was not tested.Hemolysis：Generally speaking,hemolytic crisis was not observed after 1 hour,and hemolytic rate was less than 5%.Intramuscular implantation：Infection did not occur in any animals,and materials were not discharged at all.Four weeks later,muscles were closely integrated with materials.A certain quantity of tissue grew into material pore,and peripheral muscle still had normal morphology and structure.Subacute toxicity：There was no significant difference in body mass and blood routine before and 2 weeks after testing.HE staining demonstrated that necrotic focus and other lesion were not observed in heart,liver,and kidney tissues under optic microscope.The results suggested that nano-ZrO2-HA was non-toxicity,and it had no pyrogen and hemolysis effect,as well as it did not stimulate to the muscle of rabbit.Inflammatory rejection did not happen to the animal.The nano-ZrO2-HA was closely integrated with the muscle,characterizing by great biocompatibility.Therefore,it can be used as substitution materials in clinical experiment.But it still needs to be evaluated completely.