磷酸钙骨水泥作为骨形成蛋白载体修复节段性骨缺损及相关研究

目的 制备CPC/BMP复合人工骨，通过动物实验研究其对骨缺损的修复作用及相关问题，探讨临床应用的可能性。方法 参考有关文献方法合成CPC，并将其作为BMP的载体制成CPC/BMP复合物，植入兔桡骨15mm骨缺损处，术后不同时间处死动物。通过生物力学测定，组织学染色分析，电镜扫描及X射线电子能谱分析。X线摄片，无机质含量测定以及骨密度测定等手段观察新骨形成和材料降解情况。同时以单纯的CPC及空白组作为对照研究。综合评价CPC/BMP对骨缺损的修复能力及对机体的影响。结果 术后CPC/BMP和CPC两组动物均无毒性反应。随着时间的延长，血清中碱性磷酸酶浓度逐渐升高，尤以CPC/BMP组显著，提示CPC/BMP复合物和单纯的CPC均可以促进新骨形成，前者新骨形成量大，骨修复能力明显好于后者。CPC/BMP植入2周时可见大量间充质细胞分化，在材料与骨端之间出现一层软骨细胞。4周时软骨细胞向编织骨分化，16周时板骨层骨长人材料并与之相互分割包裹，24周时骨缺损初步修复，新骨密度明显高于CPC组，说明BMP的加入不仅有效地促进了新骨的形成，同时也加速了新骨的钙化。24周组标本生物力学测定结果表明，新骨形成的同时伴随材料的降解，CPC组材料降解速度缓慢，CPC/BMP组降解速度优于CPC组，但24周时仍有部分材料残存。在新骨形成和材料降解过程中可出现血清钙浓度的一过性升高。结论 CPC是BMP的理想载体。CPC/BMP生物活性人工骨对骨缺损有较强的修复能力，可望成为新型的骨缺损修复材料。

An exoerimental and related research of segmental bone defects repaired with calcium phosphate cement as carrier to bone morphogenetic protein

Objective A new type of bone graft material was constructed by combining calcium phosphate cement(CPC) with bone morphogenetic protein(BMP). In order to evaluate the feasibility to use this material to repair the segmental bone defect in clinic, the ability of CPC was compared with CPC/BMP in bone defects reconstruction by animal experiments. Methods The model of 15 mm bone defect was established in the middle shaft of the radius in 60 rabbits, of which 30 defects were implanted with CPC/BMP composites, 22 implanted with CPC, and the other 8 rabbits served as control group. The specimens were harvested separately at the end of 2, 4, 8, 16 and 24 weeks after operation. In order to observe the formation of new bone and the degradation process of the material, a series of examinations were carried out including of radiography, histomorphology, serum detection, energy dispersion analysis X-ray(EDAX), scanning electron microscope(SEM),bone density detection, mechanical measurement and inorganic substance detection. The results of CPC group and CPC/BMP group were compared on the same condition. Results All the animals survived after operation, and no reactions of toxicity were found. New bone formation was observed to be increasing significantly in CPC/BMP group with the time of implantation. Only little new bone formed in CPC group and no healing was found in the control group. By the end of 24 weeks, new bone had bridged the gap between the proximal and distal fragments in CPC/BMP group. In histomorphological detection, chondrocytes were found at the 2nd week, and woven bone at 4th week in CPC/BMP group. Remodeling of new lamellar bone and absorption of the composite material were observed at the 16th week, and the mechanical strength of the composite material reached almost to normal level at the 24th week. Calcification was significantly higher in CPC/BMP group than that in CPC group examined by EDAX, new bone density detection and measurement of inorganic substance in specimens. During the repairing process of bone defect, the material degraded while new bone formed, the speed of degradation of CPC/BMP was evidently higher than that of CPC group. Moreover, in the process of CPC degradation, the concentration of calcium in serum increased, and the concentration of phosphate in serum kept unchanged. Conclusion The CPC/BMP composite has great potential in bone defects repairing and could be used as a material for bone graft substitute in clinical patients.