生物玻璃和壳聚糖改性的多孔活性骨水泥体内实验研究

IN VlVO EXPERIMENT OF POROUS BIOACTIVE BONE CEMENT MODIFIED BY BIOGLASS AND CHITOSAN

目的探讨新型多孔活性骨水泥(porous bioactive bone cement,PBC)在体内的生物力学特性,观察材料降解及新骨形成情况。方法将聚甲基丙烯酸甲酯(polymethylmethacrylate,PMMA)粉末、生物玻璃粉末和壳聚糖颗粒按照不同质量百分比(W/W,%)比例配制成3种PBC:PBCⅠ(50︰40︰10)、PBCⅡ(40︰50︰10)和PBCⅢ(30︰60︰10)。32只10月龄新西兰大白兔,雌雄不限,体重4.0～4.5 kg;制备直径4 mm、深10 mm的双侧股骨髁部缺损模型。动物模型随机分为4组(n=8),分别于双侧缺损处植入单纯PMMA骨水泥(A组)、PBCⅠ(B组)、PBCⅡ(C组)和PBCⅢ(D组)。术后观察实验动物一般情况,1周时行膝关节正侧位X线片检查,3、6个月取标本行生物力学测试和Van-Gieson染色组织学观察;取未植入的对应骨水泥行生物力学测试,作为对照。结果实验动物均存活至实验完成。1周X线片检查示各组植入骨水泥位置良好。生物力学测试示,植入前及术后3、6个月,C、D组压缩强度和弹性模量均较A组明显下降(P<0.05);B组压缩强度及3、6个月弹性模量较A组明显下降(P<0.05);C、D组间差异无统计学意义(P>0.05)。植入前及术后3个月,C、D组两指标均较B组明显下降(P<0.05);6个月,C组压缩强度和D组弹性模量较B组明显下降(P<0.05)。与植入前相比,B、C、D组术后3、6个月两指标均显著下降(P<0.05),A组无显著变化(P>0.05)。组织学观察示,术后3个月,A组纤维结缔组织环绕在PMMA和骨组织之间;B、C、D组壳聚糖颗粒有不同程度降解,其中D组降解最明显;6个月,A组较前无明显变化;B、C、D组可见骨组织沿壳聚糖降解后形成的空隙向骨水泥内部生长,C、D组骨生长优于B组。定量分析显示,A、B、C、D组骨组织含量百分比呈逐渐上升趋势,且各组内术后6个月显著高于3个月。结论以PMMA粉末、生物玻璃粉末和壳聚糖颗粒按照质量百分比(W/W,%)40︰50︰10及30︰60︰10比例制备的PBC较单纯PMMA骨水泥具有更好的生物相容性及生物力学特性。

Objective To investigate the biomechanical properties of porous bioactive bone cement （PBC） in vivo and to observe the degradation of PBC and new bone formation histologically. Methods According to the weight percentage （W/W, %） of polymethylmethacrylate （PMMA） to bioglass to chitosan, 3 kinds of PBS powders were obtained： PBC I （50 ： 40 ： 10）, PBC II （40 ： 50 ： 10）, and PBC III （30 ： 60 ： 10）. The bilateral femoral condylar defect model （4 mm in diameter and 10 mm in depth） was established in 32 lO-month-old New Zealand white rabbits （male or female, weighing 4.0-4.5 kg）, which were randomly divided into 4 groups （n=8）; pure PMMA （group A）, PBC I （group B）, PBC II （group C）, and PBC III （group D） were implanted in the bilateral femoral condylar defects, respectively. Gross observation were done after operation. X-ray films were taken after 1 week. At 3 and 6 months after operation, the bone cement specimens were harvested for mechanical test and histological examination. Four kinds of unplanted cement were also used for biomechanical test as control. Results M1 rabbits survived to the end of experiment. The X-ray films revealed the location of bone cement was at the right position after 1 week. Before implantation, at 3 months and 6 months after operation, the compressive strength and elastic modulus of groups C and D decreased significantly when compared with those of group A （P 〈 0.05）, but no significant difference was found between groups C and D （P 〉 0.05）; the compressive strength at each time point and elastic modulus at 3 and 6 months of group B decreased significantly when compared with those of group A （P 〈 0.05）. Before implantation and at 3 months after operation, the compressive strength and elastic modulus of groups C and D decreased significantly when compared with those of group B （P 〈 0.05）; at 6 months after operation, the compressive strength of group C and the elastic modulus of group D were significantly lower than those of group B （P 〈 0.05）. The compressive strength and elastic modulus at 3 and 6 monthsafter operation significantly decreased when compared with those before implantation in groups B, C, and D （P 〈 0.05）, but no significant difference was found in group A （P 〈 0.05）. At 3 months after operation, histological observation showed that a fibrous tissue layer formed between the PMMA cement and bone in group A, while chitosan particles degraded with different levels in groups B, C, and D, especially in group D. At 6 months after operation, chitosan particles partly degraded in groups B, C, and D with an amount of new bone ingrowth, and groups C and D was better than group B in bone growth; group A had no obvious change. Quantitative analysis results showed that the bone tissue percentage was gradually increased in the group A to group D, and the bone tissue percentage at 6 months after operation was significantly higher than that at 3 months within the group. Conclusion According to the weight percentage （W/W, %） of PMMA to bioglass to chitosan, PBCs made by the composition of 40 ： 50 ： 10 and 30 ： 60 ： 10 have better biocompatibility and biomechanical properties than PMMA cement, it may reduce the fracture risk of the adjacent vertebrae after vertebroplasty.