以I型胶原缓释rhBMP-2复合新型多孔硫酸钙支架修复兔大段桡骨缺损的实验研究
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摘要
目的:研究以Ⅰ型胶原缓释重组人骨形态发生蛋白-2(Recombinant human bonemorphogenetic protein-2,rhBMP-2)复合新型多孔硫酸钙支架对兔大段桡骨缺损的修复作用。
方法:
1.采用本课题组栗树伟等人用有机泡沫浸渍工艺及制备的新型多孔硫酸钙支架。
2.选用36只新西兰大白兔,制成72侧双前肢15mm的桡骨骨缺损模型,随机分为四组:A组植入新型多孔硫酸钙支架、B组植入复合Ⅰ型胶原的新型多孔硫酸钙支架、C组植入复合Ⅰ型胶原与rhBMP-2的新型多孔硫酸钙支架、D组植入自体骨;在术后4、8、12周随机处死动物,作下列检测:大体观察、X线检查、X线片的计算机图像分析、骨密度检测、组织学检测、组织切片的计算机图像分析、生物力学检测并对以上结果进行统计学分析。
结果:
1.X线及组织切片检查:术后各时相点皮质骨实现连接、髓腔再通、新生骨组织面积、成熟骨小梁数量C组优于B组,B组优于A组。12w时C组的骨修复及骨改建效果与D组基本相当。
2.X线片的计算机图像分析:术后各时相点X片灰度值C组优于B组(P＜0.05)和A组(P＜0.01);B组优于A组(P＜0.05);D组在4w时优于C组(P＜0.05),在8w、12w时D组与C组相比无统计学差异(P＞0.05)。
3.骨密度检测:术后各时相点骨密度值C组优于B组(P＜0.05)和A组(P＜0.01);B组优于A组(P＜0.05);D组在4w、8w时优于C组(P＜0.05),在12w时D组与C组相比无统计学差异(P＞0.05)。
4.组织切片的计算机图像分析:术后各时相点成骨面积所占比例C组优于B组(P＜0.05)和A组(P＜0.01);B组优于A组(P＜0.05);D组在4w时优于C组(P＜0.05),在8w、12w时D组与C组相比无统计学差异(P＞0.05)。
5.生物力学检测:术后12w,行三点弯曲试验,最大应力值C组优于B组(P＜0.05)和A组(P＜0.01),B组优于A组(P＜0.05);C组和D组比较无统计学差异(P＞0.05)。
结论:
1.以Ⅰ型胶原缓释rhBMP-2复合新型多孔硫酸钙支架组对兔大段桡骨缺损的修复效果与自体骨移植组相比无统计学差异,优于其他组。
2.Ⅰ型胶原可以优化新型多孔硫酸钙支架的性能。
Objective: To research the repairing effect of large segmental bone defects of radius in rabbits by new porous calcium sulfate scaffold combined with release controlled recombinant human bone morphogenetic protein-2 by Collagen I.
Methods: 1. Adopt the new porous calcium sulfate scaffold made by LI Shuwei through polymeric sponge impregnation process and the modified method. 2. Choose 36 rabbits' radial bone for seventy-two bone defect models, the defect is 15mm ,then embed the support .The rabbits are randomly classified into four groups. Group C is the experiment group ,embed the new porous calcium sulfate scaffold combined with release controlled recombinant human bone morphogenetic protein-2 by Collagen I; Group A、B、D are the control group , embed new porous calcium sulfate scaffold、new porous calcium sulfate scaffold combined with Collagen I and autogenous bone individually. After operation the animals are separately sacrificed in the forth ,eighth, twelfth week .Then, carry out the following examination: X-ray examination, X-ray image analysis, bone mineral density detection, histology observation,histology image analysis, vitodynamics detection.
Result: 1. The result of roentgenographic and histological examination: in each time point the group C were superior in term of the aera and the trabecular amount of new bone formed on region of bone defect to group A and B, the group B were superior to group A.In the twelfth week the repair of bone defects has no significant difference between the group C and the group D. 2. The result of X-ray image analysis: in each time point the group C were superior in term of X-ray gray value to group A (P<0.01) and B (P<0.05 ) ,the group B were superior to group A(P<0.05) . In the forth week the group D were superior to group C (P<0.05) but in the eighth and twelfth week the X-ray gray value has no significant difference between the group C and the group D(P>0.05). 3. The result of bone mineral density detection: in each time point the group C were superior to group A (P<0.01) and B (P<0.05) , the group B were superior to group A(P<0.05) ; In the forth and eighth week the group D were superior to group C (P<0.05) but in the twelfth week the bone mineral density has no significant difference between the group C and the group D (P>0.05) . 4. The result of histology image analysis: in each time point the group C were superior in term of the proportion of osteogenesis area to group A (P<0.01) and B(P<0.05), the group B were superior to group A (P<0.05); In the forth week the group D were superior to group C (P<0.05) but in the eighth and twelfth week the proportion of osteogenesis area has no significant difference between the group C and the group D (P>0.05) . 5. The result of vitodynamics detection: in the twelfth week the group C were superior in term of crushing strength to group A (P<0.01) and B (P<0.05 ) , the group B were superior to group A (P<0.05); The crushing strength has no significant difference between the group C and the group D (P>0.05) .
Conclusion: 1. Like autogenous bone embeding group new porous calcium sulfate scaffold combined with release controlled recombinant human bone morphogenetic protein-2 by Collagen I can efficiently repair bone defects,it was more rapid and vigorous than other group.2. Collagen I can optimize the performance of the new porous calcium sulfate scaffold.
方法:
1.采用本课题组栗树伟等人用有机泡沫浸渍工艺及制备的新型多孔硫酸钙支架。
2.选用36只新西兰大白兔,制成72侧双前肢15mm的桡骨骨缺损模型,随机分为四组:A组植入新型多孔硫酸钙支架、B组植入复合Ⅰ型胶原的新型多孔硫酸钙支架、C组植入复合Ⅰ型胶原与rhBMP-2的新型多孔硫酸钙支架、D组植入自体骨;在术后4、8、12周随机处死动物,作下列检测:大体观察、X线检查、X线片的计算机图像分析、骨密度检测、组织学检测、组织切片的计算机图像分析、生物力学检测并对以上结果进行统计学分析。
结果:
1.X线及组织切片检查:术后各时相点皮质骨实现连接、髓腔再通、新生骨组织面积、成熟骨小梁数量C组优于B组,B组优于A组。12w时C组的骨修复及骨改建效果与D组基本相当。
2.X线片的计算机图像分析:术后各时相点X片灰度值C组优于B组(P＜0.05)和A组(P＜0.01);B组优于A组(P＜0.05);D组在4w时优于C组(P＜0.05),在8w、12w时D组与C组相比无统计学差异(P＞0.05)。
3.骨密度检测:术后各时相点骨密度值C组优于B组(P＜0.05)和A组(P＜0.01);B组优于A组(P＜0.05);D组在4w、8w时优于C组(P＜0.05),在12w时D组与C组相比无统计学差异(P＞0.05)。
4.组织切片的计算机图像分析:术后各时相点成骨面积所占比例C组优于B组(P＜0.05)和A组(P＜0.01);B组优于A组(P＜0.05);D组在4w时优于C组(P＜0.05),在8w、12w时D组与C组相比无统计学差异(P＞0.05)。
5.生物力学检测:术后12w,行三点弯曲试验,最大应力值C组优于B组(P＜0.05)和A组(P＜0.01),B组优于A组(P＜0.05);C组和D组比较无统计学差异(P＞0.05)。
结论:
1.以Ⅰ型胶原缓释rhBMP-2复合新型多孔硫酸钙支架组对兔大段桡骨缺损的修复效果与自体骨移植组相比无统计学差异,优于其他组。
2.Ⅰ型胶原可以优化新型多孔硫酸钙支架的性能。
Objective: To research the repairing effect of large segmental bone defects of radius in rabbits by new porous calcium sulfate scaffold combined with release controlled recombinant human bone morphogenetic protein-2 by Collagen I.
Methods: 1. Adopt the new porous calcium sulfate scaffold made by LI Shuwei through polymeric sponge impregnation process and the modified method. 2. Choose 36 rabbits' radial bone for seventy-two bone defect models, the defect is 15mm ,then embed the support .The rabbits are randomly classified into four groups. Group C is the experiment group ,embed the new porous calcium sulfate scaffold combined with release controlled recombinant human bone morphogenetic protein-2 by Collagen I; Group A、B、D are the control group , embed new porous calcium sulfate scaffold、new porous calcium sulfate scaffold combined with Collagen I and autogenous bone individually. After operation the animals are separately sacrificed in the forth ,eighth, twelfth week .Then, carry out the following examination: X-ray examination, X-ray image analysis, bone mineral density detection, histology observation,histology image analysis, vitodynamics detection.
Result: 1. The result of roentgenographic and histological examination: in each time point the group C were superior in term of the aera and the trabecular amount of new bone formed on region of bone defect to group A and B, the group B were superior to group A.In the twelfth week the repair of bone defects has no significant difference between the group C and the group D. 2. The result of X-ray image analysis: in each time point the group C were superior in term of X-ray gray value to group A (P<0.01) and B (P<0.05 ) ,the group B were superior to group A(P<0.05) . In the forth week the group D were superior to group C (P<0.05) but in the eighth and twelfth week the X-ray gray value has no significant difference between the group C and the group D(P>0.05). 3. The result of bone mineral density detection: in each time point the group C were superior to group A (P<0.01) and B (P<0.05) , the group B were superior to group A(P<0.05) ; In the forth and eighth week the group D were superior to group C (P<0.05) but in the twelfth week the bone mineral density has no significant difference between the group C and the group D (P>0.05) . 4. The result of histology image analysis: in each time point the group C were superior in term of the proportion of osteogenesis area to group A (P<0.01) and B(P<0.05), the group B were superior to group A (P<0.05); In the forth week the group D were superior to group C (P<0.05) but in the eighth and twelfth week the proportion of osteogenesis area has no significant difference between the group C and the group D (P>0.05) . 5. The result of vitodynamics detection: in the twelfth week the group C were superior in term of crushing strength to group A (P<0.01) and B (P<0.05 ) , the group B were superior to group A (P<0.05); The crushing strength has no significant difference between the group C and the group D (P>0.05) .
Conclusion: 1. Like autogenous bone embeding group new porous calcium sulfate scaffold combined with release controlled recombinant human bone morphogenetic protein-2 by Collagen I can efficiently repair bone defects,it was more rapid and vigorous than other group.2. Collagen I can optimize the performance of the new porous calcium sulfate scaffold.
引文
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[2]Stock UA,Vacanti JP.Tissue Engneering:Current State and propects[J].Ann Rev Med,2001,52:443-451。
[3]Kiberstis P,smith O,Norman C.Bone Healthin The Blance[J].Sicince,2000,289,1479。
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[5]杨志明,组织工程基础与临床[M]。第1版,成都:四川科学技术出版社,2000:110-115。
[6]裴国献.骨组织工程研究现状与趋势[J].解放军医学杂质,2002,27(6):471-474。
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