钙镁生物活性骨再生材料的研究
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摘要
本课题包括镁替代磷酸钙骨水泥(MCPC)和介孔硅酸钙镁(OMC)两种钙镁基骨修复材料的研究。
第一部分将活性氧化镁(MgO)与磷酸四钙(Ca4(PO4)2O),磷酸氢钙(CaHPO4)按照一定比例混合制备出新型的镁替代磷酸钙骨水泥。通过颗粒溶出的方法制备出MCPC多孔支架,支架材料在体外测试中表现出良好的生物降解性和细胞相容性。将MCPC多孔支架植入兔股骨缺损,支架表现出优良的生物相容性,随着植入时间的增加,材料逐步降解,12周时,材料完全降解,缺损区域被新骨所替代,材料显示出了优良的降解性和成骨能力。
第二部分利用溶胶-凝胶法制备出了介孔硅酸钙镁材料,该材料具有规整的7nm左右的介孔孔道,比表面积高达1017 m2/go OMC在Tris-HCl溶液中具有良好的溶解性,在模拟体液中浸泡7天后,表面有大量磷灰石生成,显示出了优良的体外生物活性。将材料植入兔股骨缺损,随着植入时间的增长,新骨不断生成,OMC溃散成小的碎片,逐步降解,12周后,骨缺损基本被修复。对OMC的吸附与释放药物及大分子蛋白的性能进行了研究,结果表明,跟对照组的硅酸钙镁(CMS)相比,OMC材料能够吸附大量的药物以及一定量的大分子蛋白,且对吸附的药物／蛋白有明显的缓释效果。
另外,对MCPC多孔支架和OMC的体内动物实验所获得的样本利用上海同步辐射光源进行生物医学成像研究,结果清晰直观的显示了材料逐步降解,新骨逐渐生成的过程。实验表明MCPC和OMC都是很有潜力的骨修复生物材料。
In this study, two calcium-magnesium based biomaterials were fabricated for bone repair. Magnesium substituted calcium phosphate cement (MCPC) was fabricated by adding active magnesium oxide into tetracalcium phosphate and calcium hydrogen phosphate, and MCPC porous scaffolds were prepared through particle leaching method. The scaffold shows excellent in vitro biodegradability and cell compatibility. We implanted the scaffold into rabbit femur defect, and the scaffold degraded and new bone generated with time. After 12 weeks, the scaffold degraded completely and the defect was repaired.
Ordered mesoporous calcium-magnesium silicate (OMC) was synthesized by sol-gel method. OMC possesses uniform mesochannals around 7 nm and a large surface area of 1017 m2/g. OMC has good solubility in Tris-HCl solution, after 7 days soaked in simulated body fluid (SBF), an apatite layer formed on the surface of the material, which indicate a good bioactivity. Implanted in rabbit femur defect, OMC showed good compatibility and degradability, the defect was healed after 12 weeks of implantation.
In addition, both the animal experimental specimens of MCPC scaffold and OMC were restructured into 3D images in Shanghai synchron radiation facility (SSRF). The process of bone regeneration was observed clearly and directly.
All the results indicate that both MCPC and OMC are potential biomaterials for bone regeneration.
第一部分将活性氧化镁(MgO)与磷酸四钙(Ca4(PO4)2O),磷酸氢钙(CaHPO4)按照一定比例混合制备出新型的镁替代磷酸钙骨水泥。通过颗粒溶出的方法制备出MCPC多孔支架,支架材料在体外测试中表现出良好的生物降解性和细胞相容性。将MCPC多孔支架植入兔股骨缺损,支架表现出优良的生物相容性,随着植入时间的增加,材料逐步降解,12周时,材料完全降解,缺损区域被新骨所替代,材料显示出了优良的降解性和成骨能力。
第二部分利用溶胶-凝胶法制备出了介孔硅酸钙镁材料,该材料具有规整的7nm左右的介孔孔道,比表面积高达1017 m2/go OMC在Tris-HCl溶液中具有良好的溶解性,在模拟体液中浸泡7天后,表面有大量磷灰石生成,显示出了优良的体外生物活性。将材料植入兔股骨缺损,随着植入时间的增长,新骨不断生成,OMC溃散成小的碎片,逐步降解,12周后,骨缺损基本被修复。对OMC的吸附与释放药物及大分子蛋白的性能进行了研究,结果表明,跟对照组的硅酸钙镁(CMS)相比,OMC材料能够吸附大量的药物以及一定量的大分子蛋白,且对吸附的药物／蛋白有明显的缓释效果。
另外,对MCPC多孔支架和OMC的体内动物实验所获得的样本利用上海同步辐射光源进行生物医学成像研究,结果清晰直观的显示了材料逐步降解,新骨逐渐生成的过程。实验表明MCPC和OMC都是很有潜力的骨修复生物材料。
In this study, two calcium-magnesium based biomaterials were fabricated for bone repair. Magnesium substituted calcium phosphate cement (MCPC) was fabricated by adding active magnesium oxide into tetracalcium phosphate and calcium hydrogen phosphate, and MCPC porous scaffolds were prepared through particle leaching method. The scaffold shows excellent in vitro biodegradability and cell compatibility. We implanted the scaffold into rabbit femur defect, and the scaffold degraded and new bone generated with time. After 12 weeks, the scaffold degraded completely and the defect was repaired.
Ordered mesoporous calcium-magnesium silicate (OMC) was synthesized by sol-gel method. OMC possesses uniform mesochannals around 7 nm and a large surface area of 1017 m2/g. OMC has good solubility in Tris-HCl solution, after 7 days soaked in simulated body fluid (SBF), an apatite layer formed on the surface of the material, which indicate a good bioactivity. Implanted in rabbit femur defect, OMC showed good compatibility and degradability, the defect was healed after 12 weeks of implantation.
In addition, both the animal experimental specimens of MCPC scaffold and OMC were restructured into 3D images in Shanghai synchron radiation facility (SSRF). The process of bone regeneration was observed clearly and directly.
All the results indicate that both MCPC and OMC are potential biomaterials for bone regeneration.
引文
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[3]Liu DM, Troczynski T, Tseng WJ. Water-based sol-gel synthesis of hydroxyapatite: Process development. Biomaterials.2001,22(13):1721-1730
[4]Campbell AA, Fryxell GE, Linehan JC, Graff GL. Surface-induced mineralization:A new method for producing calcium phosphate coatings. J Biomed Mater Res.1996, 32(1)111-118
[5]Philip Kastena, Julia Vogel et al. Ectopic bone formation associated with mesenchymal stem cells in a resorbable calcium deficient hydroxyapatite carrier. Biomaterials. 2005,26(29):5879-5889
[6]Kasten P, Luginbuhl R, van Griensven M, et al. Comparison of human bone marrow stromal cells seeded on calcium-deficient hydroxyapatite, X-tricalcium phosphate and demineralized bone matrix. Biomaterials.2003,24:2593-2603
[7]Sarkar AK. Phosphate cement-based fast-setting binders. American Ceramic Society Bulletin.1990,69234-238
[8]Changsheng Liu. Inorganic bone adhesion agent and its use in human hard tissue repair. U.S.Pat. No.7094286. Aug.22,2006
[9]孙卫东,王金勇,叶承荣等.傅立叶变换红外光谱对动物尿结石成份的分析研究.扬州大学学报(农业与生命科学版).2006,27(2)：56-58
[10]Sugama T, Kukacka LE. Characteristics of magnesium polyphosphate cements derived from ammonium polyphosphate solutions. Cement and Concrete Research.1983, 13:499-506
[11]Popovics S, Rajendran N, Penko M. Rapid hardening cements for repair of concrete. ACI Materials Journal.1987,84:64-73
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[13]Abdelrazig BEI, Sharp JH.A discussion of the papers on magnesia-phosphate cements by T Sugama and LE Kukacka. Cement and Concrete Research.1985,15:921-922
[14]吴子征,张键,陈统一等.磷酸镁骨粘合剂粘接骨折的实验研究.中国修复重建外科杂志,2006,20(9)：912-915][吴子征,张键,陈统一等.新型骨水泥粘接固定骨折的动物实验研究.中国临床医学,2005,12(2)：261-264
[15]吴建国,俞永林,刘昌胜等.两种无机骨水泥对家兔内脏毒性的比较研究.复旦学报(医学版),2005,32(6)：707-710
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