可注射原位成型载药植骨材料
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摘要
硫酸钙作为一种植骨材料修复骨缺损,具有良好的生物相容性、可降解吸收性、成骨能力和力学特性等。由于硫酸钙的诸多优点,可作为植骨材料,应用在开放式手术中,填充骨缺损部位,但对于可注射的硫酸钙修复骨缺损研究尚不多见。当硫酸钙以一定比例与水或水溶液混合时,可以形成均一的糊状物,使其具有可注射性。本文以医用硫酸钙为基材,在其中添加了成核剂、塑化剂、表面修饰剂,改善了材料的综合性能,研究了材料在模拟环境中的降解情况,并添加了药物使其缓慢释放,制备出了一种可注射原位成型的硫酸钙载药植骨材料。
采用二次灼烧法由二水硫酸钙(DCS)制备出了半水硫酸钙(HCS),并通过红外光谱、X-射线衍射和扫描电镜对其进行了分析。用聚乙二醇(PEG)修饰DCS作为成核剂,具有更高的稳定性及活性,可加速材料的固化。塑化剂(MC或HPMC)的加入使糊状物具有一定的润滑性,一方面有利于改善材料的可注射性,另一方面可以在体温下形成凝胶结构,改善材料的力学性能。固化后的材料的抗压强度分析及材料断面的扫描电镜分析都表明材料具有优良的性能。
固化后的材料在磷酸盐缓冲溶液(PBS)中具有适宜的降解时间,并且材料的最大吸水量与制备材料时的液相比例有关。整个降解过程中材料能始终保持初始的形状。
在材料中加入抗生素药物庆大霉素、去甲万古霉素和头孢氨卞,会影响材料固化后的晶型及力学性能。由于三种药物水溶性及其它性质上存在差异,在载药量相同的情况下,其释放时间会有所不同。在实验初期,存在药物突释的现象,而后会维持在一定浓度的范围内上下波动。在此基础上探讨了材料表面海藻酸钠膜的形成对药物释放的影响和固水海绵模拟环境下药物的释放特性。
Calcium Sulfate, as a restore material, shows biocompatibility, biodegradability, osteoconductivity and mechanical property. So the study about using Calcium Sulfate as repairing fillers for the treatment of bone defection is reported now and then, but the injectable property has not been studied so much. When Calcium Sulfate is mixed with water or solution, it becomes an injectable paste. We use Hemihydrate Calcium Sulfate(HCS)as the basic material, compound with Dehydrate Calcium Sulfate (DCS), cellulose and PEG. We have studied the in vitro degradation of the material and interfused antibiotic drugs in it to fabricate an injectable in situ solidified bone graft material.
We used secondary treatment method to fabricate HCS from DCS, and studied them by IR, X-ray diffraction and SEM. DCS was modified by PEG to accelerate the solidification of the material. Cellulose can improve the injectability and the mechanical property of the material. The compressive stress test and the SEM analysis showed that the material has excellent properties.
The material has appropriate degradation time in PBS, and the maximum water absorption is related with the water content in the material. Throughout the degradation process, the material can maintain the shape all the time.
The additive of antibiotic drugs, such as Gentamicin, Norvancomycin and Cefalexin, can affect the crystal structure and the mechanical property of the materials. Because of the nature difference among the three drugs, the release time of the drugs from the carrier was also different. Initially, the drug release was quicker, and then it maintained a certain concentration. We can control the drug release pattern by using sodium alginate and sponge simulant environment.
采用二次灼烧法由二水硫酸钙(DCS)制备出了半水硫酸钙(HCS),并通过红外光谱、X-射线衍射和扫描电镜对其进行了分析。用聚乙二醇(PEG)修饰DCS作为成核剂,具有更高的稳定性及活性,可加速材料的固化。塑化剂(MC或HPMC)的加入使糊状物具有一定的润滑性,一方面有利于改善材料的可注射性,另一方面可以在体温下形成凝胶结构,改善材料的力学性能。固化后的材料的抗压强度分析及材料断面的扫描电镜分析都表明材料具有优良的性能。
固化后的材料在磷酸盐缓冲溶液(PBS)中具有适宜的降解时间,并且材料的最大吸水量与制备材料时的液相比例有关。整个降解过程中材料能始终保持初始的形状。
在材料中加入抗生素药物庆大霉素、去甲万古霉素和头孢氨卞,会影响材料固化后的晶型及力学性能。由于三种药物水溶性及其它性质上存在差异,在载药量相同的情况下,其释放时间会有所不同。在实验初期,存在药物突释的现象,而后会维持在一定浓度的范围内上下波动。在此基础上探讨了材料表面海藻酸钠膜的形成对药物释放的影响和固水海绵模拟环境下药物的释放特性。
Calcium Sulfate, as a restore material, shows biocompatibility, biodegradability, osteoconductivity and mechanical property. So the study about using Calcium Sulfate as repairing fillers for the treatment of bone defection is reported now and then, but the injectable property has not been studied so much. When Calcium Sulfate is mixed with water or solution, it becomes an injectable paste. We use Hemihydrate Calcium Sulfate(HCS)as the basic material, compound with Dehydrate Calcium Sulfate (DCS), cellulose and PEG. We have studied the in vitro degradation of the material and interfused antibiotic drugs in it to fabricate an injectable in situ solidified bone graft material.
We used secondary treatment method to fabricate HCS from DCS, and studied them by IR, X-ray diffraction and SEM. DCS was modified by PEG to accelerate the solidification of the material. Cellulose can improve the injectability and the mechanical property of the material. The compressive stress test and the SEM analysis showed that the material has excellent properties.
The material has appropriate degradation time in PBS, and the maximum water absorption is related with the water content in the material. Throughout the degradation process, the material can maintain the shape all the time.
The additive of antibiotic drugs, such as Gentamicin, Norvancomycin and Cefalexin, can affect the crystal structure and the mechanical property of the materials. Because of the nature difference among the three drugs, the release time of the drugs from the carrier was also different. Initially, the drug release was quicker, and then it maintained a certain concentration. We can control the drug release pattern by using sodium alginate and sponge simulant environment.
引文
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[2]顾其胜,侯春林,徐政,实用医用生物材料学,上海:上海科学技术出版社,2005,3～5
[3]俞耀庭,张兴栋,生物医用材料,天津:天津大学出版社,2000,3～4
[4]魏凤春,张恒,张晓等,智能材料的开发与应用,材料导报,2006,20(6):375～378
[5]Chen Jie, Pei Yong, Yang Li-Ming, et al., Synthesis and properties of poly (N-isopropylacrylamide-co-acrylamide) hydrogels, Macromolecular Symposial, 2005, 225 (1):103～111
[6]Prymak O., Bogdanski D., Koller M., et al., Morphological characterization and in vitro biocompatibility of a porous nickel-titanium alloy, Biomaterials, 2005, 26 (29):5801～5807
[7]Bertheville B., Porous single-phase NiTi processed under Ca reducing vapor for use as a bone graft substitute, Biomaterials, 2006, 27 (8):1246～1250
[8]Hutmacher D. W., Scaffolds in tissue engineering bone and cartilage, Biomaterials, 2000, 21(24):2529～2543
[9]南开辉,王迎军,复合纳米生物医用材料的研究,材料科学与工程学报,2006,24(1):156～159
[10]Li Wan-Ju, Laurencin C. T., Caterson E. J., et al., Electrospun nanofibrous structure: A novel scaffold for tissue engineering, Journal of Biomedical Materials Research Part A, 2002, 60(4):613～621
[11]Kikuchi M., Itoh S., Ichinose S., et al., Self-organization mechanism in a bone-like hydroxyapatite/collagen nanocomposite synthesized in vitro and its biological reaction in vivo, Biomaterials, 2001, 22(13):1705～1711
[12]Gu Hai-Ying, Chen Zhong, Sa Rong-Xiao, et al., The immobilization of hepatocytes on 24nm-sized gold colloid for enhanced hepatocytes proliferation, Biomaterials, 2004, 25(17):3445～3451
[13]葛亮,苟三怀,可注射式人工骨研究进展,国外医学·骨科学分册,2005,26(4):201～204
[14]Temeno J. S., Mikos A. G., Injectable biodegradable materials for orthopedic tissue engineering, Biomaterials, 2000, 21(23):2405～2412
[15]Ooms E.M., Wolke J.G.C., Waerden J.P.C.M., et al., Trabecular bone response to injectable calcium phosphate (Ca-P) cement, Journal of Biomedical Materials Research Part A, 2002, 61(1):9～18
[16]Khairoun I., Boltong M. G., Driessens F. C. M., et al., Effect of calcium carbonate on clinical compliance of apatitic calcium phosphate bone cement, Journal of Biomedical Materials Research Part B: Applied Biomaterials, 1997, 38(4):356～360
[17]Briak H. EI, Durand D., Nurit J., et al., Study of a hydraulic dicalcium phosphate dihydrate /calcium oxide-based cement for dental applications, Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2002, 63(4):447～453
[18]Sarda S., Fernandez E., Nilsson M., et al., Kinetic study of citric acid influence on calcium phosphate bone cements as water-reducing agent, Journal of Biomedical Materials Research Part A, 2002, 61(4):653～659
[19]Horstmann W. G., Verheyen C. C. P. M., Leemans R., An injectable calcium phosphate cement as a bone-graft substitute in the treatment of displaced lateral tibial plateau fractures, Injury, 2003,34(2):141～144
[20]Ratier A., Freche M., Lacout J. L., et al., Behaviour of an injectable calcium phosphate cement with added tetracycline, International Journal of Pharmaceutics, 2004, 274(1-2):261～268
[21]Matsumine A., Kusuzaki K., Matsubara T., et al., Calcium phosphate cement in musculoskeletal tumor surgery, Journal of Surgical Oncology, 2006, 93 (3):212～220
[22]Gauthier O., Mǖller R., Stechow D., et al., In vivo bone regeneration with injectable calcium phosphate biomaterial: A three–dimensional micro-computed tomographic, biomechanical and SEM study, Biomaterials, 2005, 26 (27):5444～5453
[23]Schmitt M., Weiss P., Bourges X., et al., Crystallization at the polymer/calcium-phosphate interface in a sterilized injectable bone substitute IBS, Biomaterials, 2002, 23 (13):2789～2794
[24]Gauthier O., Bouler J. M., Weiss P., et al., Short-term effects of mineral particle sizes on cellular degradation activity after implantation of injectable calcium phosphate biomaterials and the consequences for bone substitution, Bone, 1999, 25 (2):71～74
[25]Daculsi G., Rohanizadeh R., Weiss P., et al., Crystal polymer interaction with new injectable bone substitute; SEM and Hr TEM study, Journal of Biomedical Materials Research Part A, 2000, 50 (1):1～7
[26]Amouriq Y., Bourges X., Weiss P., et al., Skin sensitization study of two hydroxypropyl methylcellulose components (Benecel and E4M) of an infectable bone substitute in guinea pigs, Journal of materials science: materials in medicine, 2002, 13 (2):149～154
[27]Gauthier O., Goyenvalle E., Bouler J.-M., et al., Macroporous biphasic calcium phosphate ceramics versus injectable bone substitute: a comparative study 3 and 8 weeks after implantation in rabbit bone, Journal of materials science: materials in medicine, 2001, 12 (5):385～390
[28]Zhao F., Lu W. W., Luk K. D. K., et al., Surface treatment of injectable strontium-containing bioactive bone cement for verterbroplasty, Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2004, 69 (1):79～86
[29]Xu H. H. K., Weir M. D., Burguera E. F., et al., Injectable and macroporous calcium phosphate cement scaffold, Biomaterials, 2006, 27 (24):4279～4287
[30]Lerouxel E., Weiss P., Giumelli B., et al., Injectable calcium phosphate scaffold and bone marrow graft for bone reconstruction in irradiated areas: An experimental study in rats, Biomaterials, 2006, 27 (26):4566～4572
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