骨组织工程用多孔羟基磷灰石及其复合材料的制备与性能
|
摘要
采用添加造孔剂法制备出骨组织工程用多孔羟基磷灰石(HA)中间层,研究了造孔剂种类、含量、温度等因素对孔径、孔隙率、力学性能的影响:应用凝胶浇铸法制备出HA-PLGA复合材料,研究了其制备工艺及其弹性模量:通过冷压与固化技术制备出HA-PLGA-TiO_2复合材料,评价了该复合材料的生物相容性。得出了以下研究结果:
1.添加单一PVB造孔剂制备的多孔HA陶瓷,其孔径较小,孔的连通性较差。
2.烧结工艺影响HA的相对密度。采用造孔剂(PVB、NH_4HCO_3和(NH_4)_2CO_3)于1200℃烧结保温4h,可以获得性能较好的多孔HA中间层。通过造孔剂的不同配比可控制多孔HA的孔隙率、孔尺寸与孔连通性。随着(NH_4)_2CO_3含量的增大,材料的压缩强度和弹性模量呈下降趋势。PVB、(NH_4)_2CO_3和NH_4HCO_3的含量分别为10vol.%、15vol.%和25vol.%时,烧结后的多孔HA生物材料具有较好的孔结构和连通性,最大孔隙率达到50.3%,压缩强度为4.4MPa,弹性模量与自然骨接近。
3.浓度、时间、温度和PH值均影响PLGA溶胶的粘度。浓度低于50g/L时,粘度随着时间的延长和温度(＜50℃)的升高变化不大;当温度高于50℃时,粘度急剧上升。浓度高于50g/L时,粘度随着时间延长和温度(＜40℃)的升高而降低;当温度高于40℃时,粘度急剧上升。PH值增大,粘度会随之增大。
4.采用凝胶浇铸法,将PLGA—HA溶胶与多孔HA复合,可获得弹性模量与自然骨相近的HA/PLGA复合材料。PLGA-HA溶胶粘度和PH值均影响PLGA与多孔HA中间层的复合。粘度为25.8mPa·S的溶胶利于复合:随着PH值减小,溶胶较易填充孔洞,但PH值小于4.289时,充填效果反而降低。
5.PLGA-HA-TiO_2复合材料中含25wt.%的HA和2.5wt.%的TiO_2时,具有好的强度和塑性。HA含量少于50wt.%时,对其在模拟体液中的降解速率基本没影响;反之,其降解速率会增加。在降解过程中,PLGA-HA-TiO_2的表面形成磷灰石,表明该复合材料具有好的生物相容性。
According to the structure and characteristics of natural bone,porous hydroxyapatite(HA)biomaterial used in bone tissue engineering was prepared. Hydroxyapatite/poly lactic-co-glycolic acid(HA/PLGA)and PLGA-HA-TiO_2 composites were prepared by gel-casting and cold pressing-solidifying,respectively. Results are shown as follows:
1.The hole size and connectivity of porous HA ceramic prepared by adding sole PVB are small and bad.This structure will be difficult to be casted by PLGA gel.
2.Relative density of HA are affected by sintering processing.The appropriate sintering condition of porous HA is at 1200℃for 4 h.And the main phase of the bulk is HA after sintering.While the volume fraction of(NH_4)_2CO_3 increases,the compressing strength and modulus of elasticity of HA decrease.Containing 10vol.%PVB,15vol.%(NH_4)_2CO_3 and 25vol.%NH_4HCO_3,the material has preferable structure with good hole connectivity and distribution.Its big hole size is over 100μm and the small hole size is in the range from 5μm to 50μm,which is favorable for cell and tissue growing and alimentation transporting.The porosity and compressing strength of HA reached 50.3%and 4.44 MPa,respectively. Modulus of elasticity of HA is near to that of natural bone.
3.The influences of concentration,time,temperature and PH value on the viscosity of the PLGA sol are rather obvious.When the concentration of PLGA is under 50g/L, the viscosity of the sol changes a little with time and temperature(＜50℃),but it increases quickly above 50℃.For the concentration of PLGA over 50g/L,the viscosity of the sol falls with time prolonging and temperature increasing(＜40℃), but it rises rapidly when the temperature is over 40℃.The higher the PH value is, the bigger viscosity of the sol is.
4.Modulus of elasticity of the HA/PLGA composites prepared by gel-casting approaches that of natural bone.This indicates that the composite may be used in the bone tissue replacing and grafting in the future.The viscosity of the sol increases with the increase of the concentration of PLGA.It is appropriate for the viscosity of the sol with 25.SmPa·S to fill in the holes of HA.In the acidic condition,the sol is easy to fill in the holes with the decrease of the PH value. However,when PH value is lower than 4.289,the filling effect is bad.
5.PLGA-HA-TiO_2 composites were successfully prepared by cold pressing and solidifying.The solidification temperature of PLGA increases with the addition of HA or TiO_2.The composites with appropriate contents of 25 wt.%HA and 2.5 wt.%TiO_2 have excellent strength accompanied with good plasticity.HA content less than 50wt.%hasn't any effect on the degradation rate of the composite in SBF, otherwise its degradation rate will be accelerated.Apatite is formed on the surface of PLGA-HA composites immersed in SBF,which shows the composites have good bioactivity in vitro.
1.添加单一PVB造孔剂制备的多孔HA陶瓷,其孔径较小,孔的连通性较差。
2.烧结工艺影响HA的相对密度。采用造孔剂(PVB、NH_4HCO_3和(NH_4)_2CO_3)于1200℃烧结保温4h,可以获得性能较好的多孔HA中间层。通过造孔剂的不同配比可控制多孔HA的孔隙率、孔尺寸与孔连通性。随着(NH_4)_2CO_3含量的增大,材料的压缩强度和弹性模量呈下降趋势。PVB、(NH_4)_2CO_3和NH_4HCO_3的含量分别为10vol.%、15vol.%和25vol.%时,烧结后的多孔HA生物材料具有较好的孔结构和连通性,最大孔隙率达到50.3%,压缩强度为4.4MPa,弹性模量与自然骨接近。
3.浓度、时间、温度和PH值均影响PLGA溶胶的粘度。浓度低于50g/L时,粘度随着时间的延长和温度(＜50℃)的升高变化不大;当温度高于50℃时,粘度急剧上升。浓度高于50g/L时,粘度随着时间延长和温度(＜40℃)的升高而降低;当温度高于40℃时,粘度急剧上升。PH值增大,粘度会随之增大。
4.采用凝胶浇铸法,将PLGA—HA溶胶与多孔HA复合,可获得弹性模量与自然骨相近的HA/PLGA复合材料。PLGA-HA溶胶粘度和PH值均影响PLGA与多孔HA中间层的复合。粘度为25.8mPa·S的溶胶利于复合:随着PH值减小,溶胶较易填充孔洞,但PH值小于4.289时,充填效果反而降低。
5.PLGA-HA-TiO_2复合材料中含25wt.%的HA和2.5wt.%的TiO_2时,具有好的强度和塑性。HA含量少于50wt.%时,对其在模拟体液中的降解速率基本没影响;反之,其降解速率会增加。在降解过程中,PLGA-HA-TiO_2的表面形成磷灰石,表明该复合材料具有好的生物相容性。
According to the structure and characteristics of natural bone,porous hydroxyapatite(HA)biomaterial used in bone tissue engineering was prepared. Hydroxyapatite/poly lactic-co-glycolic acid(HA/PLGA)and PLGA-HA-TiO_2 composites were prepared by gel-casting and cold pressing-solidifying,respectively. Results are shown as follows:
1.The hole size and connectivity of porous HA ceramic prepared by adding sole PVB are small and bad.This structure will be difficult to be casted by PLGA gel.
2.Relative density of HA are affected by sintering processing.The appropriate sintering condition of porous HA is at 1200℃for 4 h.And the main phase of the bulk is HA after sintering.While the volume fraction of(NH_4)_2CO_3 increases,the compressing strength and modulus of elasticity of HA decrease.Containing 10vol.%PVB,15vol.%(NH_4)_2CO_3 and 25vol.%NH_4HCO_3,the material has preferable structure with good hole connectivity and distribution.Its big hole size is over 100μm and the small hole size is in the range from 5μm to 50μm,which is favorable for cell and tissue growing and alimentation transporting.The porosity and compressing strength of HA reached 50.3%and 4.44 MPa,respectively. Modulus of elasticity of HA is near to that of natural bone.
3.The influences of concentration,time,temperature and PH value on the viscosity of the PLGA sol are rather obvious.When the concentration of PLGA is under 50g/L, the viscosity of the sol changes a little with time and temperature(＜50℃),but it increases quickly above 50℃.For the concentration of PLGA over 50g/L,the viscosity of the sol falls with time prolonging and temperature increasing(＜40℃), but it rises rapidly when the temperature is over 40℃.The higher the PH value is, the bigger viscosity of the sol is.
4.Modulus of elasticity of the HA/PLGA composites prepared by gel-casting approaches that of natural bone.This indicates that the composite may be used in the bone tissue replacing and grafting in the future.The viscosity of the sol increases with the increase of the concentration of PLGA.It is appropriate for the viscosity of the sol with 25.SmPa·S to fill in the holes of HA.In the acidic condition,the sol is easy to fill in the holes with the decrease of the PH value. However,when PH value is lower than 4.289,the filling effect is bad.
5.PLGA-HA-TiO_2 composites were successfully prepared by cold pressing and solidifying.The solidification temperature of PLGA increases with the addition of HA or TiO_2.The composites with appropriate contents of 25 wt.%HA and 2.5 wt.%TiO_2 have excellent strength accompanied with good plasticity.HA content less than 50wt.%hasn't any effect on the degradation rate of the composite in SBF, otherwise its degradation rate will be accelerated.Apatite is formed on the surface of PLGA-HA composites immersed in SBF,which shows the composites have good bioactivity in vitro.
引文
[1][日]筏义人.Tissue Engineering:Fundamentals and Applications[M].Beijing:Science Press,2007.
[2]Crane G M,Lshaug S L,Mikos A G,et al.Bone tissue engineering[J].Nature Medicine,1995,1(12):1322-1326.
[3]李彦林,杨志明,解慧琪.生物衍生组织工程骨支架材料的制备及理化特性[J].生物医学工程学杂志,2002,19(1):10-12.
[4]张阳德 编著.纳米生物材料学[M].北京:化学化工出版社,2005.
[5]Tancred D C,Carr A J,Mccormack B A O.Deve-lopment of a new synthetic bone graft[J].J Mater Sci:Mater Med,1998(10):819-823.
[6]Leize E M,Hemmerle J.Voegel J C.Characterization analyses of acorl collagen composite used for bone-replacement graft material[J].J Mater Med,1999(10):47-51.
[7]邱明才.骨结构与骨代谢[J].医用生物力学,1995,10(4):253-256.
[8]Ibim S E M,Uhrich K E.Attawia M,et al.Preliminary in vivo report on the osteocompatibility of poly (anhydride-co-imides)evaluated in a tibial model[J].J Biomed Mater Res.1998,43(4):374-379.
[9]Bonfield W,Wang M,Tanner K E.Interfaces in Analogue Biomaterials[J].Acta mater,1998,46(7):2509-2518.
[10]Hench L L.Bioceramics[J].J Am Ceram Soc,1998,81(7):1705-1728.
[11]Sanchez-Salcedo S,Nieto A,Vallet-Regi M.Hydroxyapatite/β-tricalcium phosphate/agarose macroporous scaffolds for bone tissue engineering[J].Chemical Engineering Journal.2008,137(1):62-71.
[12]Sinae Kim,Sang-Soo Kim,Soo-Hong Lee,et al.In vivo bone formation from human embryonic stem cell-derived osteogenic cells in poly(d,l-lactic-co-glycolic acid)/hydroxyapatite composite scaffolds[J].Biomaterials,2008,29(8):1043-1053.
[13]俞耀庭 主编.生物医用材科(第2版)[M].天津:天津大学出版社,2001.
[14]Boccaccini A R,Roether J A,Hench L L.A composites approach to tissue engineering.In:Lin H T and Sing M,editors.26~(th)Annual Conference on Composites,Advanced Ceramics,Materials,and Structures:B.Florida:The American Ceramic Society,2002,23(4):805-816.
[15]Wang M.Developing bioactive composite materials for tissue re placement[J].Biomaterials,2003,24:2133-2151.
[16]范颂鸣,陈鸿辉,谭建伟,等.新型骨修复生物活性材料-固骼生的应用体会[J].中国矫形外科杂志,2004,12(23):1819-1821.
[17]Thomson R C,Shung A K,Yaszemski M J,et al.Polymer Scaffold Process[M].In:Lanza R P,Langer R and Vacanti J editors.Principles of Tissue Engineering(Seconed Edition).California:Academic Press,2000.
[18]Minfang Chen,Junjun Tan,Yuying Lian,et al.Preparation of Gelatin coated hydroxyapatite nanorods and the stability of its aqueous colloidal[J].Applied Surface Science,2008,254(9):2730-2735.
[19]Yuejun Tang,Yuefeng Tang,ChunTang Lv,et al.Preparation of uniform porous hydroxyapatite biomaterials by a new method[J].Applied Surface Science,2008,254(17):5359-5362.
[20]Sujatha Pushpakanth,Balaji Srinivasan,Sreedhar B,et al.An in situ approach to prepare nanorods of titania-hydroxyapatite(TiO_2-HAp)nanocomposite by microwave hydrothermal technique[J].Materials Chemistry and Physics,2008,107(2-3):492-498.
[21]Mizuno M,Shindo M,Kobayashi D,et al.Osteogenesis by bone marrow stromal cells maintained on type Ⅰcollagen matrix gels invivo[J].Bone,1997,20(2):101-107.
[22]Sims C D,Butler P E,Cao Y L,et al.Tissue engineered neocartilage using plasms derived polymer substrates and chondrocytes[J].Plast Reconstr Surg,1998,101(6):1580-1585.
[23]Lahiji A,Sohrabi A,Hungerford D S.Chitosan supports the expression of extracellular matrix proteins in human osteoblasts and chondrocytes[J].J Biomed Mater Res,2000,51(4):586-595.
[24]韩雪峰,杨大平,郭铁芳,等.纤维蛋白胶塑形、异体微粒软骨脱细胞基质支架的人工软骨研究[J].中国临床康复,2005,9(2):56-58.
[25]Hutmacher D W.Mechanical properties and cell cultural response of polycaprolactone scaffolds designed and fabricated via fused deposition modeling[J].J Biomed Mater Res,2001,55(2):203-216.
[26]Zein I,Hutmacher D W,Tan K C,et al.Fused deposition modeling of novel scaffold architectures for tissue engineering application[J].Biomaterials,2002,3(4):1169-1185.
[27]汪朝阳,赵耀明,郑绿茵,等.生物降解材料聚(乳酸-乙醇酸)研究进展[J].江苏化工,2005,33(22):9-12.
[28]吴其胜.纳米HAP改性PMMA骨水泥力学性能的研究[J].材料科学与工程学报,2005,23(6):863-866.
[29]陈晓明,李世普,罗泽波,等.α-TCP骨水泥水化产物的生物相容性研究[J].中国生物医学工程学报.1996,15(3):233-236.
[30]Shi D L.Biomaterials and Tissue Engineering[M].Beijing:Tsinghua University Press,2004.
[31]Jun Goshima,Victor M.Goldberg,Arnold I.Caplan,et al.Osteogenic potential of culture-expanded rat marrow cells as assayed in vivo with porous calcium phosphate ceramic[J].Biomaterials,1991,12(2):253-258.
[32]Tancred D C,McCormack B A O,Carr A J.A synthetic bone implant macroscopically identical to cancellous bone[J].Biomaterials,1998,19:2303-2311.
[33]Yoshikawa T,Ohgushi H,Tamai S.Immediate bone Forming capability of prefabricated osteogenic hydroxyapatite[J].J Biomed Mater Res,1996,32(3):481-492.
[34]曹罡,陶凯,毛天球,等.生物降解性骨组织工程支架材料-可吸收性珊瑚羟基磷灰石[J].医学研究生学报,2005,18(3):212-217.
[35]Zhang Y,Zhang M.Synthesis and characterization of macroporous chitosan/caicium phosphate composite scaffolds for tissue engineering[J].J Biomed Mater Res.2001,55(3):304-312.
[36]Lee Y M,Park Y J,Lee S J.Tissue engineered bone formation using chitosan/tricalcium phosphate sponges[J].J Periodontol,2000,71(3):410-417.
[37]Shikinami Y,HataK,Okuno M.Ultrahigh-strength resorbable implants made from bioactive ceramic particles/polylactide composites[M].Bioceramics,1996.
[38]Laurencin C T,Attawia M A,ElgendyH E,et al.Tissue engineered bone-regeneration using degradable polymers:the formation of mineralized matrices[J].Bone,1996,19(suppll):93S-99S.
[39]成兰,陈萍萍,周为,等.聚DL-乳酸/纳米羟基磷灰石复合多孔支架材料的制备及其相容性研究[C].重庆:2005年中国机械工程学会年会论文集,2005,37.
[40]付东伟,闫玉华.生物可降解医用材料的研究进展[J].生物骨科材料与临床研究,2005,2(2):39-42.
[41]王勃生,孙福玉,孟庆恩,等.第三代生物医学材料的研究与开发[J].材料科学与工程,1994,12(1):1-4.
[42]Urist M R,Kovacs S,Yates K A.Regeneration of an enchondroma defects under the influence of an implant of human bone morphogenetic protein[J].J Hand Surg,1986,11(3):417-419.
[43]Louwerse R T,Heyligers I C,Klein N J,et al.Use of recombinant human osteogenic protein-1 for the repair of subchondral defects in articular cartilage in goats[J].J Biomed Mater Res,2000,49(4):506-516.
[44]谭祖键,李起鸿,许建中,等.BMP诱导成骨过程中胶原生成及TGF-β_1的促进作用[J].第三军医大学学报,2002,24(5):521-523.
[45]卜丽莎,李建军,高申,等.转染BMP-2基因的兔BMSCs种植PLA/PCL支架体外构建组织工程骨[J].中国矫形外科杂志,2004,12(9):677-679.
[46]刘梅.胶原基骨组织工程支架材料实现人体组织的修复和替代[J].天津科技,2005(1):62.
[47]Thomson R C,Shung A K,Yaszemski M J,et al.Polymer Scaffold Process[C].In:Lanza R P,Langer R and Vacati J editors.Principles of Tissue Engineering(Second Edition).California:Academic Press,2000.
[48]Hutmacher D W.Polymeric scaffolds in tissue engineering bone and cartilage[J].Biomaterials,2000,21:2529-2543.
[49]Mooney D J,Mazzoni C L,Breuer C,et al.Stabilized Polyglycolic Acid Fibre Based Tubes for Tissue Engineering[J].Biomaterials,1996,17(2):115-124.
[50]Liao C J,Chen C F,Chen J H,et al.Solvent effects on the microstructure and properties of 75/25 poly (D,L-lactide-coglycolide)tissue scaffolds[J].Journal of Biomedical Materials Research,2002,59(4):676-681.
[51]赵瑾,袁晓燕,姚康德.组织工程多孔支架制备技术进展[J].化工进展,2001,3:351-355.
[52]Sheridan M H,Shea L D,Mooney D J,et al.Bioabsorbable Polymer Scaffolds for Tissue Engineering Icapable of Sustained Growth Factor Delivery[J].Journal of Controlled Release,2000,64:91-102.
[53]Hutmacher D W.Polymeric scaffolds in tissue engineering bone and cartilage[J].Biomaterials,2000,21:2529-2543.
[54]高建平,马朋高,于九皋,等.组织工程与生物可降解高分子骨架[J].高分子通报,2000,4:89-95.
[55]Park A,Wu B,Griffith L G.Journal of Biomaterials Science[J].Polymer edition,1998,9(2):89-110.
[56]姚秀敏,谭寿洪,江东亮.多孔羟基磷灰石陶瓷的制备[J].无机材料学报,2000,15(3):467-472.
[57]朴英杰.加强基础研究促进组织工程学协调发展[J].中国临床解剖学杂志,2005,23(1):3-4.
[58]葛泉波,何淑兰,毛津淑,等.生物材料与细胞相互作用及表面修饰[J].化学通报,2005(1):43-48.
[59]徐立新,石宗利,史雪婷,等.CPP/α-TCP骨水泥复合材料研究[J].兰州大学学报(自然科学版),2004,40(3):22-25.
[60]李世普 编著.生物医用材料导论[M].武汉:武汉工业大学出版社,2000.
[61]徐淑华,工迎军,罗承萍.TZP增韧HA复合材料的电镜研究[J].华南理工大学学报(自然科学版),2002,30(3):35-39.
[62]Mooney D J,Park S,Kaufmann P M,et al.Biondegradable sponges for hepatoevte transplantation[J].J Biomed Mater Res,1995,29:959-965.
[63]Tracy M A.Development anscale-up ofa microspherc protein delivery system[J].Biotecamol Pro,1998,14:108-116.
[64]颖芳,康浩方,张震.钛合金医用植入物材料的研究及应用[J].稀有金属,2001,25(5):349-354.
[65][德]C.莱茵斯,M.皮特尔斯 主编,陈振华 译.钛与钛合金[M]北京:化学工业出版社,2005.
[66]温波,黄颖,徐勇忠.氧化钛生物陶瓷骨细胞相容性研究[J].吉林大学学报(医学版),2004,30(3):418-424.
[67]Harmand M F,Bordenave L,BareilleR,et al.In vitro evaluation of an expoxy resin's cytocompatility using cells and human differentiated cells[J].J Biomaterials Sci Polym Ed,1991,2(1):67-77.
[68]陈腾飞,龚伟平,颜焕元,等.炭纤维涂敷TiO_2增强羟基磷灰石复合材料的微观结构研究[J].矿冶工程,2006,26(4):58-60.
[69]Almirall A,Larrecq G,Delgado J A,et al.Fabrication of low temperature macroporous hydroxyapatite scaffolds by foaming and hydrolysis of an α-TCP paste[J].Biomaterials,2004,25:3671-3680.
[70]张玉军,尹衍升,王迎军.羟基磷灰石及其复合生物陶瓷材料研究进展[J].生物医学工程学杂志(增刊),1999,16:37-39.
[71]朱新文,江东亮.有机泡沫浸渍工艺——一种经济实用的多孔陶瓷制备工艺[J].盐酸盐通报.2000,14(10):308-310.
[72]刘富德,陈森凤,张书政,等.多孔陶瓷材料的发展状况[J].材料导报,2000,14(6):33-34.
[73]刘学建,黄莉萍,占宏晨,等.陶瓷成型方法研究进展[J].陶瓷学报,1999,20(4):230-234.
[74]黄培云 主编.粉末冶金原理(第2版)[M].北京:冶金工业出版社,1997.
[75]储成林,朱景川,尹钟大,等.致密羟基磷灰石(HA)生物陶瓷烧结行为和力学性能[J].功能材料,1999,30(6):606-609.
[76]张丽娜.纳米羟基磷灰石及其复合材料的制备与性能[D].青岛:青岛大学,2004.
[77]王莉丽,马楚凡,赵康.凝胶成型法制备多孔羟基磷灰石生物陶瓷及其性能研究[J].材料科学与工程学报,2006,24(1):148-151.
[78]Verheyen C,Wijn J,Blitterswijk C et al.Hydroxylapatite/poly(L-lactide)composites:an animal study on push-out strengths and interface histology.J Biomed Mater Res,1993,27:433-444.
[79]Verheyen C,Wijn J,Blitterswijk C et al.Evaluation of hydroxylapatite/poly(L-lactide)composites:mechanical behavior[J].J Biomed Mater Res,1992,26:1277-1296.
[80]郭晓东,郑启新,杜靖远,等.可吸收羟基磷灰石/聚DL-乳酸复合骨折内固定材料的生物相容性研究[J]. 生物医学工程学杂志,1999,16(2):135-139.
[81]Hench L L.Sol-gel materials for bioceramics application[J].Current Opinion in Solid State and Materials Science,1999,604-610.
[82]田心,毕平编著.生物力学基础[M].北京:科学出版社,2007.
[83]Devin J E,Attawia M A,Laurencin C T.Three dimensional degradable porous polymerceramic matrices for use in bone repair[J].J Biomater Sci Polymer,1996,7(8):661-669.
[84]Newman KD,McBurney MW.Poly(D,L lactic-co-glycolic acid)microspheres as biodegradable microcarriers for pluripotent stem cells[J].Biomaterials,2004,25:5763-5771.
[85]Laurencin CT,Attawia MA,Lu LQ,et al.Poly(lactide-co-glycolide)/hydroxyapatite delivery of BMP-2-producing cells:a regional gene therapy approach to bone regeneration[J].Biomaterials,2001,22:1271-1277.
[86]Sepulveda P.Gelcasting foams for porous ceramica[J].Am Ceram Soc Bull,1997,76:61-65.
[87]Li H S,De Wijn J R,Layrolle P,et al.Synthesis of macro-porous hydroxyapatite scaffolds for bone tissue engineering[J].J Biomed Mater Res,2002,61:109-120.
[88]王莉丽,赵康,陈水楠.凝胶成型法制备多孔羟基磷灰石生物陶瓷[J].硅酸盐通报,2005,24(2):110-112.
[89]Yunzhi Yang,Joo L.Ong,Jiemo Tian.Rapids intering of hydroxyapatite by microwave processing[J].Journal of Materials Science Letters,2002,21(1):67-69.
[90]王卓薇,王志强,孙稚菁,刘智.羟基磷灰石的微波烧结[J].大连轻工业学院学报,2007,26(2):147-151.
[2]Crane G M,Lshaug S L,Mikos A G,et al.Bone tissue engineering[J].Nature Medicine,1995,1(12):1322-1326.
[3]李彦林,杨志明,解慧琪.生物衍生组织工程骨支架材料的制备及理化特性[J].生物医学工程学杂志,2002,19(1):10-12.
[4]张阳德 编著.纳米生物材料学[M].北京:化学化工出版社,2005.
[5]Tancred D C,Carr A J,Mccormack B A O.Deve-lopment of a new synthetic bone graft[J].J Mater Sci:Mater Med,1998(10):819-823.
[6]Leize E M,Hemmerle J.Voegel J C.Characterization analyses of acorl collagen composite used for bone-replacement graft material[J].J Mater Med,1999(10):47-51.
[7]邱明才.骨结构与骨代谢[J].医用生物力学,1995,10(4):253-256.
[8]Ibim S E M,Uhrich K E.Attawia M,et al.Preliminary in vivo report on the osteocompatibility of poly (anhydride-co-imides)evaluated in a tibial model[J].J Biomed Mater Res.1998,43(4):374-379.
[9]Bonfield W,Wang M,Tanner K E.Interfaces in Analogue Biomaterials[J].Acta mater,1998,46(7):2509-2518.
[10]Hench L L.Bioceramics[J].J Am Ceram Soc,1998,81(7):1705-1728.
[11]Sanchez-Salcedo S,Nieto A,Vallet-Regi M.Hydroxyapatite/β-tricalcium phosphate/agarose macroporous scaffolds for bone tissue engineering[J].Chemical Engineering Journal.2008,137(1):62-71.
[12]Sinae Kim,Sang-Soo Kim,Soo-Hong Lee,et al.In vivo bone formation from human embryonic stem cell-derived osteogenic cells in poly(d,l-lactic-co-glycolic acid)/hydroxyapatite composite scaffolds[J].Biomaterials,2008,29(8):1043-1053.
[13]俞耀庭 主编.生物医用材科(第2版)[M].天津:天津大学出版社,2001.
[14]Boccaccini A R,Roether J A,Hench L L.A composites approach to tissue engineering.In:Lin H T and Sing M,editors.26~(th)Annual Conference on Composites,Advanced Ceramics,Materials,and Structures:B.Florida:The American Ceramic Society,2002,23(4):805-816.
[15]Wang M.Developing bioactive composite materials for tissue re placement[J].Biomaterials,2003,24:2133-2151.
[16]范颂鸣,陈鸿辉,谭建伟,等.新型骨修复生物活性材料-固骼生的应用体会[J].中国矫形外科杂志,2004,12(23):1819-1821.
[17]Thomson R C,Shung A K,Yaszemski M J,et al.Polymer Scaffold Process[M].In:Lanza R P,Langer R and Vacanti J editors.Principles of Tissue Engineering(Seconed Edition).California:Academic Press,2000.
[18]Minfang Chen,Junjun Tan,Yuying Lian,et al.Preparation of Gelatin coated hydroxyapatite nanorods and the stability of its aqueous colloidal[J].Applied Surface Science,2008,254(9):2730-2735.
[19]Yuejun Tang,Yuefeng Tang,ChunTang Lv,et al.Preparation of uniform porous hydroxyapatite biomaterials by a new method[J].Applied Surface Science,2008,254(17):5359-5362.
[20]Sujatha Pushpakanth,Balaji Srinivasan,Sreedhar B,et al.An in situ approach to prepare nanorods of titania-hydroxyapatite(TiO_2-HAp)nanocomposite by microwave hydrothermal technique[J].Materials Chemistry and Physics,2008,107(2-3):492-498.
[21]Mizuno M,Shindo M,Kobayashi D,et al.Osteogenesis by bone marrow stromal cells maintained on type Ⅰcollagen matrix gels invivo[J].Bone,1997,20(2):101-107.
[22]Sims C D,Butler P E,Cao Y L,et al.Tissue engineered neocartilage using plasms derived polymer substrates and chondrocytes[J].Plast Reconstr Surg,1998,101(6):1580-1585.
[23]Lahiji A,Sohrabi A,Hungerford D S.Chitosan supports the expression of extracellular matrix proteins in human osteoblasts and chondrocytes[J].J Biomed Mater Res,2000,51(4):586-595.
[24]韩雪峰,杨大平,郭铁芳,等.纤维蛋白胶塑形、异体微粒软骨脱细胞基质支架的人工软骨研究[J].中国临床康复,2005,9(2):56-58.
[25]Hutmacher D W.Mechanical properties and cell cultural response of polycaprolactone scaffolds designed and fabricated via fused deposition modeling[J].J Biomed Mater Res,2001,55(2):203-216.
[26]Zein I,Hutmacher D W,Tan K C,et al.Fused deposition modeling of novel scaffold architectures for tissue engineering application[J].Biomaterials,2002,3(4):1169-1185.
[27]汪朝阳,赵耀明,郑绿茵,等.生物降解材料聚(乳酸-乙醇酸)研究进展[J].江苏化工,2005,33(22):9-12.
[28]吴其胜.纳米HAP改性PMMA骨水泥力学性能的研究[J].材料科学与工程学报,2005,23(6):863-866.
[29]陈晓明,李世普,罗泽波,等.α-TCP骨水泥水化产物的生物相容性研究[J].中国生物医学工程学报.1996,15(3):233-236.
[30]Shi D L.Biomaterials and Tissue Engineering[M].Beijing:Tsinghua University Press,2004.
[31]Jun Goshima,Victor M.Goldberg,Arnold I.Caplan,et al.Osteogenic potential of culture-expanded rat marrow cells as assayed in vivo with porous calcium phosphate ceramic[J].Biomaterials,1991,12(2):253-258.
[32]Tancred D C,McCormack B A O,Carr A J.A synthetic bone implant macroscopically identical to cancellous bone[J].Biomaterials,1998,19:2303-2311.
[33]Yoshikawa T,Ohgushi H,Tamai S.Immediate bone Forming capability of prefabricated osteogenic hydroxyapatite[J].J Biomed Mater Res,1996,32(3):481-492.
[34]曹罡,陶凯,毛天球,等.生物降解性骨组织工程支架材料-可吸收性珊瑚羟基磷灰石[J].医学研究生学报,2005,18(3):212-217.
[35]Zhang Y,Zhang M.Synthesis and characterization of macroporous chitosan/caicium phosphate composite scaffolds for tissue engineering[J].J Biomed Mater Res.2001,55(3):304-312.
[36]Lee Y M,Park Y J,Lee S J.Tissue engineered bone formation using chitosan/tricalcium phosphate sponges[J].J Periodontol,2000,71(3):410-417.
[37]Shikinami Y,HataK,Okuno M.Ultrahigh-strength resorbable implants made from bioactive ceramic particles/polylactide composites[M].Bioceramics,1996.
[38]Laurencin C T,Attawia M A,ElgendyH E,et al.Tissue engineered bone-regeneration using degradable polymers:the formation of mineralized matrices[J].Bone,1996,19(suppll):93S-99S.
[39]成兰,陈萍萍,周为,等.聚DL-乳酸/纳米羟基磷灰石复合多孔支架材料的制备及其相容性研究[C].重庆:2005年中国机械工程学会年会论文集,2005,37.
[40]付东伟,闫玉华.生物可降解医用材料的研究进展[J].生物骨科材料与临床研究,2005,2(2):39-42.
[41]王勃生,孙福玉,孟庆恩,等.第三代生物医学材料的研究与开发[J].材料科学与工程,1994,12(1):1-4.
[42]Urist M R,Kovacs S,Yates K A.Regeneration of an enchondroma defects under the influence of an implant of human bone morphogenetic protein[J].J Hand Surg,1986,11(3):417-419.
[43]Louwerse R T,Heyligers I C,Klein N J,et al.Use of recombinant human osteogenic protein-1 for the repair of subchondral defects in articular cartilage in goats[J].J Biomed Mater Res,2000,49(4):506-516.
[44]谭祖键,李起鸿,许建中,等.BMP诱导成骨过程中胶原生成及TGF-β_1的促进作用[J].第三军医大学学报,2002,24(5):521-523.
[45]卜丽莎,李建军,高申,等.转染BMP-2基因的兔BMSCs种植PLA/PCL支架体外构建组织工程骨[J].中国矫形外科杂志,2004,12(9):677-679.
[46]刘梅.胶原基骨组织工程支架材料实现人体组织的修复和替代[J].天津科技,2005(1):62.
[47]Thomson R C,Shung A K,Yaszemski M J,et al.Polymer Scaffold Process[C].In:Lanza R P,Langer R and Vacati J editors.Principles of Tissue Engineering(Second Edition).California:Academic Press,2000.
[48]Hutmacher D W.Polymeric scaffolds in tissue engineering bone and cartilage[J].Biomaterials,2000,21:2529-2543.
[49]Mooney D J,Mazzoni C L,Breuer C,et al.Stabilized Polyglycolic Acid Fibre Based Tubes for Tissue Engineering[J].Biomaterials,1996,17(2):115-124.
[50]Liao C J,Chen C F,Chen J H,et al.Solvent effects on the microstructure and properties of 75/25 poly (D,L-lactide-coglycolide)tissue scaffolds[J].Journal of Biomedical Materials Research,2002,59(4):676-681.
[51]赵瑾,袁晓燕,姚康德.组织工程多孔支架制备技术进展[J].化工进展,2001,3:351-355.
[52]Sheridan M H,Shea L D,Mooney D J,et al.Bioabsorbable Polymer Scaffolds for Tissue Engineering Icapable of Sustained Growth Factor Delivery[J].Journal of Controlled Release,2000,64:91-102.
[53]Hutmacher D W.Polymeric scaffolds in tissue engineering bone and cartilage[J].Biomaterials,2000,21:2529-2543.
[54]高建平,马朋高,于九皋,等.组织工程与生物可降解高分子骨架[J].高分子通报,2000,4:89-95.
[55]Park A,Wu B,Griffith L G.Journal of Biomaterials Science[J].Polymer edition,1998,9(2):89-110.
[56]姚秀敏,谭寿洪,江东亮.多孔羟基磷灰石陶瓷的制备[J].无机材料学报,2000,15(3):467-472.
[57]朴英杰.加强基础研究促进组织工程学协调发展[J].中国临床解剖学杂志,2005,23(1):3-4.
[58]葛泉波,何淑兰,毛津淑,等.生物材料与细胞相互作用及表面修饰[J].化学通报,2005(1):43-48.
[59]徐立新,石宗利,史雪婷,等.CPP/α-TCP骨水泥复合材料研究[J].兰州大学学报(自然科学版),2004,40(3):22-25.
[60]李世普 编著.生物医用材料导论[M].武汉:武汉工业大学出版社,2000.
[61]徐淑华,工迎军,罗承萍.TZP增韧HA复合材料的电镜研究[J].华南理工大学学报(自然科学版),2002,30(3):35-39.
[62]Mooney D J,Park S,Kaufmann P M,et al.Biondegradable sponges for hepatoevte transplantation[J].J Biomed Mater Res,1995,29:959-965.
[63]Tracy M A.Development anscale-up ofa microspherc protein delivery system[J].Biotecamol Pro,1998,14:108-116.
[64]颖芳,康浩方,张震.钛合金医用植入物材料的研究及应用[J].稀有金属,2001,25(5):349-354.
[65][德]C.莱茵斯,M.皮特尔斯 主编,陈振华 译.钛与钛合金[M]北京:化学工业出版社,2005.
[66]温波,黄颖,徐勇忠.氧化钛生物陶瓷骨细胞相容性研究[J].吉林大学学报(医学版),2004,30(3):418-424.
[67]Harmand M F,Bordenave L,BareilleR,et al.In vitro evaluation of an expoxy resin's cytocompatility using cells and human differentiated cells[J].J Biomaterials Sci Polym Ed,1991,2(1):67-77.
[68]陈腾飞,龚伟平,颜焕元,等.炭纤维涂敷TiO_2增强羟基磷灰石复合材料的微观结构研究[J].矿冶工程,2006,26(4):58-60.
[69]Almirall A,Larrecq G,Delgado J A,et al.Fabrication of low temperature macroporous hydroxyapatite scaffolds by foaming and hydrolysis of an α-TCP paste[J].Biomaterials,2004,25:3671-3680.
[70]张玉军,尹衍升,王迎军.羟基磷灰石及其复合生物陶瓷材料研究进展[J].生物医学工程学杂志(增刊),1999,16:37-39.
[71]朱新文,江东亮.有机泡沫浸渍工艺——一种经济实用的多孔陶瓷制备工艺[J].盐酸盐通报.2000,14(10):308-310.
[72]刘富德,陈森凤,张书政,等.多孔陶瓷材料的发展状况[J].材料导报,2000,14(6):33-34.
[73]刘学建,黄莉萍,占宏晨,等.陶瓷成型方法研究进展[J].陶瓷学报,1999,20(4):230-234.
[74]黄培云 主编.粉末冶金原理(第2版)[M].北京:冶金工业出版社,1997.
[75]储成林,朱景川,尹钟大,等.致密羟基磷灰石(HA)生物陶瓷烧结行为和力学性能[J].功能材料,1999,30(6):606-609.
[76]张丽娜.纳米羟基磷灰石及其复合材料的制备与性能[D].青岛:青岛大学,2004.
[77]王莉丽,马楚凡,赵康.凝胶成型法制备多孔羟基磷灰石生物陶瓷及其性能研究[J].材料科学与工程学报,2006,24(1):148-151.
[78]Verheyen C,Wijn J,Blitterswijk C et al.Hydroxylapatite/poly(L-lactide)composites:an animal study on push-out strengths and interface histology.J Biomed Mater Res,1993,27:433-444.
[79]Verheyen C,Wijn J,Blitterswijk C et al.Evaluation of hydroxylapatite/poly(L-lactide)composites:mechanical behavior[J].J Biomed Mater Res,1992,26:1277-1296.
[80]郭晓东,郑启新,杜靖远,等.可吸收羟基磷灰石/聚DL-乳酸复合骨折内固定材料的生物相容性研究[J]. 生物医学工程学杂志,1999,16(2):135-139.
[81]Hench L L.Sol-gel materials for bioceramics application[J].Current Opinion in Solid State and Materials Science,1999,604-610.
[82]田心,毕平编著.生物力学基础[M].北京:科学出版社,2007.
[83]Devin J E,Attawia M A,Laurencin C T.Three dimensional degradable porous polymerceramic matrices for use in bone repair[J].J Biomater Sci Polymer,1996,7(8):661-669.
[84]Newman KD,McBurney MW.Poly(D,L lactic-co-glycolic acid)microspheres as biodegradable microcarriers for pluripotent stem cells[J].Biomaterials,2004,25:5763-5771.
[85]Laurencin CT,Attawia MA,Lu LQ,et al.Poly(lactide-co-glycolide)/hydroxyapatite delivery of BMP-2-producing cells:a regional gene therapy approach to bone regeneration[J].Biomaterials,2001,22:1271-1277.
[86]Sepulveda P.Gelcasting foams for porous ceramica[J].Am Ceram Soc Bull,1997,76:61-65.
[87]Li H S,De Wijn J R,Layrolle P,et al.Synthesis of macro-porous hydroxyapatite scaffolds for bone tissue engineering[J].J Biomed Mater Res,2002,61:109-120.
[88]王莉丽,赵康,陈水楠.凝胶成型法制备多孔羟基磷灰石生物陶瓷[J].硅酸盐通报,2005,24(2):110-112.
[89]Yunzhi Yang,Joo L.Ong,Jiemo Tian.Rapids intering of hydroxyapatite by microwave processing[J].Journal of Materials Science Letters,2002,21(1):67-69.
[90]王卓薇,王志强,孙稚菁,刘智.羟基磷灰石的微波烧结[J].大连轻工业学院学报,2007,26(2):147-151.