羟基磷灰石/外消旋聚乳酸复合材料生物活性和生物相容性的体内实验

背景：外消旋聚乳酸在体内最主要的降解机制是水解,其与羟基磷灰石复合后,复合材料的生物降解率及失重率是否会有所改善。 目的：观察羟基磷灰石/外消旋聚乳酸复合材料体内植入兔股骨缺损后随时间延长界面及结构的变化。 设计：随机分组对照观察。 单位：武汉理工大学生物材料与工程研究中心。 材料：选用40只健康成年日本大耳白兔,体质量2.0～2.5kg,雌雄各半,由湖北省动物实验中心提供合格证号：SCXK（鄂）2003-0005]。 方法：实验于2005-06/2006-03在湖北生物材料工程技术研究中心完成。①随机摸球法将大耳白兔分成2组：羟基磷灰石/外消旋聚乳酸组和外消旋聚乳酸对照组,每组20只。各组实验兔麻醉后,于兔左前肢股骨髁部分别将羟基磷灰石/外消旋聚乳酸及外消旋聚乳酸圆柱体植入骨腔洞内,圆柱体可略高于骨质表面。用骨膜覆盖样本材料,复位皮肤及骨膜组织瓣。②实验评估：两组实验兔于造模后3,6,12及24周将植入材料及周围骨组织完整取出,使用扫描电子显微镜进行观察各材料内植入后随时间延长界面及结构的变化。主要观察指标：两组材料内植入后随时间延长界面及结构的变化。 结果：纳入实验兔40只均进入结果分析。材料植入体内后,羟基磷灰石颗粒从材料表面脱落,成纤维细胞向组织内长入,并伴有少量新生骨痂的形成,显示羟基磷灰石/外消旋聚乳酸复合材料具有一定的成骨性和骨连接性。在植入24周时界面观察显示,材料被组织分隔包裹,新生骨组织长入材料,骨愈合情况良好,显示羟基磷灰石/外消旋聚乳酸材料具有良好的生物相容性。对于可生物降解的外消旋聚乳酸聚合物,体内水解是最主要的降解机制,其降解速率由于与羟基磷灰石材料的复合而减小。羟基磷灰石/外消旋聚乳酸复合材料具有成骨和骨连接能力。 结论：羟基磷灰石/外消旋聚乳酸复合材料具有成骨性和骨连接性;由于复合材料降解速率减小而相应改善了其生物相容性;羟基磷灰石/外消旋聚乳酸复合材料适合临床应用于可吸收内固定材料。

Bioactivity and biocompatibility of hydroxyapatite/DL-poly lactic acid composite: In vivo implantation

BACKGROUND:Hydrolysis in vivo is the key mechanism of degradation in DL-polylactic acid (PDLLA). When it is combined with hydroxyapatite (HA), could the biodegradation and weight loss rate be improved? OBJECTIVE: To observe the changes in the interface and structure of HA/PDLLA composite after in vivo implantation into rabbit femoral defects.DESIGN: Randomized grouping and controlled observation.SETTING: Biomedical Materials and Engineering Research Center, Wuhan University of Technology.MATERIALS: Forty healthy adult Japan White Rabbits of 2.0-2.5 kg, either male or female were provided by the Animal Experimental Center of Hubei Province (No. SCXK. 2003-0005).METHODS: The experiment was conducted in Biomedical Materials and Engineering Research Center, Wuhan University of Technology from June 2005 to March 2006. ①The rabbits were randomly divided into two groups: HA/PDLLA group and PDLLA control group with 20 animals in each group. After anesthetized with ketamine and proazamine, the sample rods of HA/PDLLA and PDLLA were respectively implanted into the drilled bone cavities (φ5 mm × 8 mm) among condyles of femur sites of the rabbits, and the rod could be slightly higher than the surface of bone substance. The samples were covered by periosteum and skin, and then the skin and periosteum were repositioned. ②The complete implants and peripheral bone tissues were taken out respectively after 3, 6, 12 and 24 weeks implantation. The changes in the interface and structure of HA/PDLLA composite after in vivo implantation were observed by using scanning electron microscope (SEM, JSM-5610LV, Japan).MAIN OUTCOME MEASURES: Changes in the interface and structure of HA/PDLLA composite after in vivo implantation.RESULTS: Totally 40 rabbits were involved in the result analysis. After the materials were implanted, HA granules shed from the material surface, some fibroblasts grew into the tissue and a little new osteotylus was formed, indicating HA/PDLLA composite had capabilities of bone-formation and bone-connection. After 24 weeks implantation, the material was divided and wrapped by tissues, neogenetic bone tissue grew into the material, and the fracture healed well,indicating HA/PDLLA composite had good biocompatibility. As for biodegradable PDLLA polymer, hydrolysis in vivo is the most main mechanism of degradation; the degradation speed was decreased owing to being compounded with HA.CONCLUSION: HA/PDLLA composite has capabilities of bone-formation and bone-connection; the biocompatibility of the composite is improved accordingly on account of the decrease of the degradation speed. HA/PDLLA composite is suitable for clinical application as absorbable materials for internal fixation.