无机活性元素骨组织工程支架材料修复山羊颌骨缺损

Reconstructing goat mandible defects with inorganic active element bone grafts

目的:应用无机活性元素骨组织工程支架材料,对山羊的下颌骨角部大型箱状缺损施行骨重建,观察支架材料骨构建效能和生物相容性的情况。方法:实验于2004-02/12在安徽医科大学附属省立医院实验中心及相关实验室完成。①实验材料:无机活性元素骨组织工程支架材料由美国波士顿大学分子生物相容学研究室研制提供;21只雌性健康山羊由安徽医科大学动物实验中心(皖医实动准字01号)提供,实验过程中动物处置符合动物伦理学标准。②实验方法:取山羊15只,按4,8,12周3个时间点分为3组,位下颌角部手术制备30 mm×25 mm×10 mm的大型箱状缺损。采用自身配对设计,左侧置入支架材料为实验组,右侧空白对照为对照侧;剩余6只山羊为对照组,不手术。③观察指标:术后4,8,12周应用X射线片、组织学和放射性核素显像观察缺损区新骨形成情况;并测定骨密度;应用血液学检查及骨髓基质细胞体外复合细胞培养评价材料的生物相容性。结果:①一般观察:实验山羊无手术死亡,创口Ⅰ期愈合。②X射线片:实验侧有渐进性骨密度增高,阻射影逐级增强,对照侧呈透光阴影。③放射性核素显像:实验侧有较明显的核浓聚和再生血管化现象,对照侧无骨重建,故无骨代谢变化。④骨密度测量系数:实验侧呈递增式上升,对照侧维持较低水平,提示无自发性成骨。⑤组织学观察:实验侧呈时间递增性骨重建现象,在12周时新骨已完全形成并钙化基本完成,而对照侧直到12周仍无成骨现象。⑥生物相容性:各组的血常规、细胞形态、生化和相关酶学指标均在正常范围内。结论:无机活性元素骨组织工程支架材料有良好的成骨和再血管化功能,且生物相容性好,提示由该支架材料诱导的组织工程化骨构建有望成为临床骨组织大型缺损的替代材料。

AIM： To discuss the efficacy and biocompatibility of inorganic active element bone tissue engineering grafts in repairing big box defects in goat＇s mandible angle. METHODS： The experiment was carried out in the Experimental Center and Related Laboratory, Anhui Provincial Hospital Affiliated to Anhui Medical University from February to December in 2004. （1）Inorganic active element bone tissue engineering grafts were provided by the Department of Molecular Biocompatibility in Boston University; 21 female healthy goats were offered from the Experimental Animal Center in Anhui Medical University. All the managements were in accordance with the ethical standard of animals. （2）Fifteen goats were operated on both sides of mandible angle to prepare the big box defects of 30 mm×25 mm×10 mm, with inorganic active element bone tissue engineering grafts put into the left side （graft side） and blank control into the right side （control side） using the matched-pairs design. Fifteen goats with defects were divided into three groups according to the three time points of 4, 8, 12 weeks. While other 6 goats were served as control group, without the operation.（3）At 4, 8, 12 weeks postoperatively, the goats were examined by X-ray, histological detection and radionuclide imaging to observe the new bone formation in defect area; bone density was measured; the biocompatibility of materials was evaluated by hematological test and marrow stroma cell culture. RESULTS： （1）General observation： No goats died on operation, and the wound healed well at Ⅰ period.（2）X-ray： Bone density increased gradually and the X-ray shadow expanded in graft side, while control side presented lucent shadow.（3） Radionuclide imaging： In graft side, there were obvious uptakes of the ^99mTc-MDP and revascularization; In control side, there was no process of bone regeneration and bone metabolism. （4）Bone density in graft side increased by degrees, while that in control side maintained at low level, showing no auto-osteogenic phenomenon.（5）Histological detection： Bone defects of graft side had the process of progressing osteogenesis along with the time, calcification and bone marrow formation occurred at 12 weeks. No bone formation was found in control side.（6）Biocompatibility： The blood routine, cell morphology, biochemistry and related enzymological index were all normal in each sample.CONCLUSION： Inorganic active element bone tissue engineering grafts have good function on auto-osteogenesis and revascularization, as well as good biocompatibility. So these grafts will be the main materials in clinic of repairing bone tissue engineering defects.