羟基磷灰石／聚乳酸-三亚甲基碳酸酯软腭植入材料的生物相容性与安全性

Biocompatibility and safety of hydroxyapatite and poly (d,l-lactide-co-trimethylene carbonate) complex palatal implant material

背景:软腭植入材料目前多采用聚对苯二甲酸乙二醇酯,由于其价格昂贵,且有轻度排斥反应,远期的生物学效应也尚不肯定,限制了其临床应用。目的:与聚对苯二甲酸乙二醇酯对照,评价羟基磷灰石/聚乳酸-三亚甲基碳酸酯复合材料软腭植入材料的生物相容性与安全性。设计、时间及地点:随机分组设计、动物对照实验,于2006-10/2007-05在解放军广州军区总医院医学实验科生物人工骨实验室及广州医学院实验动物中心完成。材料:羟基磷灰石为解放军广州军区总医院医学实验科生物人工骨实验室研制,聚乳酸-三亚甲基碳酸酯为济南岱罡生物科技有限公司产品,聚对苯二甲酸乙二醇酯(长1cm,直径2mm)为广州军区总医院耳鼻喉科提供。利用有机溶剂注模法研制羟基磷灰石/聚乳酸-三亚甲基碳酸酯复合材料。方法:选择SD大鼠60只,分别将聚对苯二甲酸乙二醇酯、羟基磷灰石/聚乳酸-三亚甲基碳酸酯复合材料植入20只大鼠背部左、右肌肉内;分别将羟基磷灰石颗粒、聚乳酸-三亚甲基碳酸酯植入20只大鼠背部左、右肌肉内;其余20只大鼠进行同样的手术,但不植入任何材料作为对照。主要观察指标:术后分别于14,30,60,90d取材料及周围组织和鼠心、肝、肾标本,进行大体标本观察和组织学检查。结果:60只大鼠均进入结果分析。羟基磷灰石、聚乳酸-三亚甲基碳酸酯材料界面的炎性反应较重,聚乳酸-三亚甲基碳酸酯可在体内缓慢降解;聚对苯二甲酸乙二醇酯、羟基磷灰石/聚乳酸-三亚甲基碳酸酯复合材料界面无明显炎症反应,与周围组织结合紧密,组织可长入材料的微孔内,两者在观察时间内无明显降解吸收。4种材料均对局部组织及全身重要器官(心、肝、肾)无严重损害。结论:羟基磷灰石/聚乳酸-三亚甲基碳酸酯复合材料的生物相容性和安全性与聚对苯二甲酸乙二醇酯相当,优于羟基磷灰石、聚乳酸-三亚甲基碳酸酯材料。

BACKGROUND： Currently commonly used palatal implant material is polyethylene terephthalate （PET）, but its clinical application is restricted due to its high price, mild rejection reaction and uncertain long-term biological effect. OBJECTIVE： To evaluate the biocompatibility and safety of hydroxyapatite and poly （d,l-lactide-co-trimethylene carbonate）complex （HA-P） palatal implant material versus PET, DESIGN, TIME AND SETTING： The randomized controlled animal experiment was performed between October 2006 and May 2007 at Biological and Artificial Bone Laboratory, Department of Medical Experiment, General Hospital of Guangzhou Military Area Command of Chinese PLA and Experimental Animal Center of Guangzhou Medical University, Guangzhou, Guangdong Province, China, MATERIALS： Hydroxyapatite （HA） was obtained from Biological and Artificial Bone Laboratory, Department of Medical Experiment, General Hospital of Guangzhou Military Area Command of Chinese PLA （China）, Poly （d,l-lactide-co-trimethylene carbonate） （DL-TMC） was produced by Jinan Daigang Biotechnology Co, Ltd. （China）. PET, 1 cm in length and 2 mm in diameter, was provided by Department of Otolaryngology, General Hospital of Guangzhou Military Area Command of Chinese PLA （China）. HA-P was made using organic solvent injection mould. METHODS： Sixty Sprague-Dawley rats were selected for the experiment. Twenty rats were implanted PET and HA-P into left and right back muscles, respectively, Twenty rats were implanted HA and DL-TMC into left and right back muscles, respectively. Another twenty rats left were performed the same operation but implanted nothing as control. MAIN OUTCOME MEASURES： At 14, 30, 60, 90 days postoperation, implanted materials, surrounding tissues, rat heart, liver and kidney specimens were observed through gross specimen observation and histological examination. RESULTS： All 60 rats were involved in result analysis. Inflammatory reactions of HA and DL-TMC were relatively severe and DL-TMC could degrade in vivo slowly. There was no significant inflammatory reaction of PET and HA-P, They combined closely with surrounding tissue and tissue could grow into moicropores of material, PET and HA-P had no significant degradation during observation period, HA, PET, HA-P and DL-TMC were not harmful to local tissue and systemic organs, CONCLUSION： The biocompatibility and safety of HA-P was similar to PET, but better than HA and DL-TMC.