多孔钽复合BMP-7修复兔软骨及软骨下骨缺损的实验研究

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目的 研究多孔钽与BMP-7复合后对兔关节软骨及软骨下骨缺损修复的作用,探讨其软骨修复能力及与宿主组织的生物相容性.方法 取成年新西兰大耳白兔48只,随机分为3组(n=16),制备兔股骨内髁软骨缺损模型,分别于右侧股骨内髁植入复合BMP-7多孔钽材料(A组)、多孔钽材料(B组)及不植入材料(C组).术后观察动物一般状况,术后4、8、16周取材行大体、组织学、扫描电镜观察,术后16周行Micro-CT观察A、B组组织空隙内软骨及骨长入情况和多孔钽周围成骨情况.结果 术后动物存活良好,手术切口均Ⅰ期愈合.大体观察示,随时间延长,A、B组术后缺损区材料表面均出现新生软骨并逐渐覆盖缺损区域,A组术后新生软骨组织出现更早,表面平整光滑,修复程度较B组好;C组术后各时间点缺损区均未修复,表面逐渐被纤维组织填充.除术后4周A、B组软骨缺损修复大体观察评分比较差异无统计学意义(P>0.05)外,术后8、16周A组评分均高于B组(P<0.05).扫描电镜观察示,随时间延长,A组材料表面新生软骨及成骨细胞数量逐渐增多,细胞外基质逐渐将材料覆盖,孔隙内长入的新生骨组织逐渐增多,A组新生骨组织及细胞外基质分泌明显多于B组.甲苯胺蓝染色组织学观察示,术后4、8、16周两组多孔钽界面新生软骨及骨组织逐渐增加,出现新生骨小梁并向材料孔隙内生长,骨组织与多孔钽接触趋于紧密,软骨缺损区域逐渐被新生软骨样组织覆盖,新生软骨组织与多孔钽结合越发紧密;A组新生软骨及骨组织多于B组.Micro-CT观测示,术后16周A组组织骨密度、骨小梁厚度、骨小梁数目、骨体积分数均高于B组,骨小梁间隙低于B组,比较差异均有统计学意义(P<0.05).结论 多孔钽具有良好的生物相容性,其与BMP-7复合后可与宿主形成稳定的连接与整合,对软骨及软骨下骨缺损修复起良好作用.“,”Objective To investigate the ability to repair osteochondral defect and the biocompatibility of porous tantalum loaded with bone morphogenetic protein 7 (BMP-7) by observing the effect of porous tantalum loaded with BMP-7 in repairing articular cartilage and subchondral bone defect.Methods The cartilage defect models of medial femoral condyle were established in 48 New Zealand white rabbits,which were randomly divided into 3 groups (n=16):porous tantalum material+BMP-7 (group A) and porous tantalum material (group B) were implanted into the right side of the medial femoral condyle;and no material was implanted as control (group C).The general condition of animals was observed after operation,then the specimens were harvested for gross observation,histological observation,and scanning electron microscope (SEM) observation at 4,8,and 16 weeks after implantation,micro-CT was used to observe the cartilage and bone ingrowth and bone formation around porous tantalum at 16 weeks after implantation.Results No animal died after operation and wound healed well.Gross observation showed that defects of groups A and B were covered with new cartilage with time,but earlier new cartilage formation and better repair were observed in group A than group B,no repair occurred at the site of bone defects,and defect surface was filled with fibrous tissue in group C.Cartilage repair gross score of group A was significantly higher than that of group B at 8 and 16 weeks (P<0.05) but no significant difference was found between groups A and B at 4 weeks (P>0.05).SEM observation showed that the number of new cartilage and osteoblasts increased gradually with time,and the implanted material was gradually covered with the extracellular matrix,and the new bone tissue grew into the pores of the material;the neonatal bone tissue and extracellular matrix secretion of group A were significantly more than those of group B.The toluidine blue staining results showed that new cartilage and bone tissue gradually increased in the porous tantalum interface,and new bone trabecula formed and grew in the pores,the bone and the porous tantalum contact tended to close,and cartilage defect was gradually covered with cartilage like tissue,cartilage tissue and porous tantalum combined more closely in groups A and B at 4,8 and 16 weeks.New cartilage and bone tissue of group A was more than that of group B.Micro-CT analysis indicated that the bone mineral density,trabecular thickness,trabecular number,and bone volume fraction of group A were significantly higher than those of group B at 16 weeks (P<0.05),but the trabecular bone space was significantly lower than that of group B (P<0.05).Conclusion The domestic porous tantalum has good biocompatibility,domestic porous tantalum loaded with BMP-7 can promote the formation of a stable connection with the host and has a good effect on cartilage and subchondral bone defect repair.
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