雾化干燥法制备羟基磷灰石微球的结构表征及其生物学行为研究
|
摘要
羟基磷灰石(HA)材料具有优异的生物相容性和生物活性,被广泛应用在生物材料的多个领域。球形HA具有特殊的多孔结构和良好的表面性能,对蛋白质、核酸、生物酶等生物活性大分子的分离和纯化具有较好的选择性。而低结晶度乃至非晶的HA微球,不仅具有流动性好、比表面积大等优点,还有较好的可降解性及优越的生物活性,能更好的应用在药物载体、细胞培养载体、骨填充、骨修复等领域。降低HA微球结晶度的途径之一就是通过改变HA料浆的参数,并快速干燥,使HA微球更多地保留原始料浆的性质。目前,空心和多孔HA微球主要通过模板法进而烧结处理制备,这导致其结晶度较高,降解速率过低。而对低结晶度、高降解速率HA微球的相关研究较少。
本文利用自制的火焰-喷雾干燥装置,以高于500℃的甲烷火焰为干燥介质,通过调整原始HA料浆的参数,得到结晶度较低、孔隙度较高的HA微球。利用扫描电子显微镜(SEM)、透射电子显微镜(TEM)、高分辨透射电镜(HRTEM)、场发射电子显微镜(FE-SEM)、X射线衍射仪(XRD)、比表面积分析仪(SSA)、激光粒度分析仪(LDPSA)、红外光谱分析仪(FTIR)等检测手段,对所得HA微球的形貌、相组成、粒度分布、比表面积、孔径分布、微观结构特征以及基团分布等进行了系统的分析研究,优化出了利用火焰-雾化干燥法制备HA微球的工艺参数。以去氨水处理后的料浆、未去氨水料浆和冰水混合物料浆为试验对象,对采用火焰-雾化干燥法制备出的三种HA微球进行体外、体内试验,研究不同结晶度和结构形态的HA微球在生物学行为上的差异。进而以未去氨水料浆火焰干燥所得的HA微球为例,利用热致相分离技术制备多孔PLLA/HA微球复合支架,系统研究了不同比例的HA微球对复合支架力学性能和生物学性能的影响。
结果表明,利用自制的火焰-喷雾干燥装置,在甲烷火焰高温干燥介质中得到的HA微球,能更多的保留HA在原料浆中的性质。原始料浆中的氨水在干燥过程中分解的氨气气体会导致HA微球结构疏松,比表面积增加,粒度分布不均。低温原始料浆干燥后,可得到低结晶度、结构疏松且粒度不均的HA微球。本试验中,冰水混合物料浆所得HA微球的结晶度为29.8%,远低于典型HA颗粒90%以上的结晶程度,且比表面积(167.16 m2/g)和总孔体积(0.5054ml/g)远高于去氨水处理后料浆所得微球(52.523 m2/g,0.2331 ml/g)。本研究可以通过调节HA料浆的参数来降低所得HA微球的结晶度,改善其结构和性能。
HA料浆的性质对火焰干燥后所得HA微球的性能有重要影响。HA在其料浆中的结晶程度和晶粒微观形貌受反应时间、沉化时间以及反应温度等因素的影响。在常温条件下,随反应时间的延长,HA的结晶程度越来越高。料浆沉化一段时间后,其中的HA纳米晶体呈针状生长。反应温度越高料浆中HA的结晶度越高。
火焰-雾化干燥HA微球的结晶程度随原始料浆中HA的结晶度升高而增加。TEM结果表明,组成去氨水料浆所得的HA微球的微颗粒呈棒状或条状分布；未去氨水料浆所得HA微球中有部分非透明的非晶存在；而冰水混合物料浆所得HA微球的晶粒存在泡状半透明球状非晶磷酸钙。另外,冰水混合物料浆所得HA微球表面存在较多疏松的微孔结构。
煅烧温度对不同性质HA料浆所得HA微球的影响程度也不相同。中低温处理(低于600℃)对去氨水处理后的料浆所得HA微球的形貌、结晶度以及比表面积没有明显影响。高温煅烧处理(800℃-1000℃)会使微球的晶粒粗化长大,并在微球内部熔合,进而明显降低其比表面积和孔体积。但是600℃低温煅烧后,冰水混合物料浆所得的微球比表面积和孔体积也会从原来的167.16m2/g,0.5054 ml/g分别急剧降至65.985 m2/g和0.1952 ml/g。
火焰干燥所得HA微球在体外生物模拟实验中的结果表明其具有较好的生物活性,并对BSA蛋白质有一定的吸附和缓释作用。SBF浸泡后HA微球的质量变化呈先减小后增加的趋势。HA微球结晶度越低,质量变化越明显。HA微球对BSA的吸附量并不是单纯地随结晶度的降低而升高,还受孔隙度和降解速率的影响。在体内生物体液作用一段时间后,火焰-雾化干燥后的HA微球无毒副作用,并和活体骨结合良好。从组织形貌分析来看,HA微球植入体具有良好的骨引导能力。植入新西兰大白兔的股骨中4个月后,三种植入体周围都形成了新的生物组织,且有不同程度的降解,降解程度随结晶度的降低而增加；未去氨水料浆所对应的HA微球植入体内部有结缔组织长入。
HA微球加入到高分子材料中能形成复合生物材料,改善高分子材料由于降解而产生的酸性环境,提高复合材料的生物学性能和力学性能。本研究将未去氨水料浆经火焰-雾化干燥法所得HA微球均匀的混入PLLA的二氧六环溶液中,利用热致相分离技术成功制备出连通度较好的多孔PLLA/HA微球复合支架。结果表明,HA微球和PLLA材料能较好的结合,且随着HA微球加入量的增加,复合支架结构的不规则程度加剧,力学性能提高。相对于纯PLLA多孔支架的压缩模量(4.4MPa),HA微球的质量比占复合支架的30%时,复合支架的压缩模量(9.1MPa)最高。在SBF中浸泡一段时间后,支架表面会形成类骨磷灰石,并且其沉积量随HA微球含量的增加而增加。同时,HA微球的加入还能提高复合支架对BSA蛋白质的吸附能力。
大鼠的MC3T3成骨细胞4周的培养后,在PLLA/HA微球复合支架上能较好的粘附、分化和繁殖。由于HA微球具有优异的生物活性和良好的润湿性,加入后能使细胞更好的在复合支架材料上分化和繁殖。组织学切片也表明,PLLA/HA微球复合支架中的部分细胞能够长入到支架内部,和材料融合状态良好。
Hydroxyapatite (HA) can be widely used for repair and replacement of damaged or traumatized bone tissues due to its good biocompatibility and bioactivity. With specific porous structure and good surface properties, spherical HA has been potentially applied on the field of separation and purification for bioactivity macromolecules, such as proteins, nucleic acids and enzymes. The lower crystallinity or amorphous HA microspheres (HAM) has broad application prospect not only because of its good flowability and high specific surface area, but also its biodegradable and excellent bioactivity. One of method reducing the crystallinity of HAM is through changing the properties of HA slurries and rapid solidification, which can retain much more characteristic of original HA slurry in the HAM. The low crystallinity HAM can be used for drug delivery, cell culture carrier, bone filter, bone repair and other fields because of its good properties. So far, hollow and porous HAM mainly has been fabricated primarily by the template method and then calcinated it. However, almost no degradable HAM with high crystallinity could be prepared using this mehod. The relevant reports about preparation and characterization of lower crystallinity of HAM are very rare.
In this study, HAM with low crystallinity and high porosity were fabricated by the flame-drying method with self-made device using methane flame as the drying medium. The microstructure, phase component and other performances of HAM were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), transmission electron microscopy (TEM), laser diffraction particle size analyzer (LDPSA), surface area analyzer (SSA), and fourier transform infrared spectrum analyzer (FTIR). Besides, the parameters of the flame-drying method were systematically optimized in the process of HAM fabrication. Three kinds of HAM were fabricated by that flame-drying method using HA slurries with ammonia (AHAs), without ammonia (NAHAs) and under ice-water condition (IWHAs), respectively. The in vitro and vivo experiments of HAM were discussed for studying the biological behavior differences with different crystallinity and microstructure. Furthermore, taking the HAM by the NAHAs as the supplement, porous PLLA/HAM composite scaffolds were fabricated by the thermally induced phase separation technology. Then the effect of content of HAM in the composite scaffolds on their mechanical and biological properties was systematically researched in this paper.
The results indicated that HAM has been retained more performances of HA crystal in the slurry under higher drying medium using self-made flame-drying device. According to these results, it could reduce the crystallinity of HAM and improve its structural properties through changing HA slurries parameters. In this paper, HAM by the AHAs has the regular spherical structure, smooth surface morphology, smaller particle size range and highest crystallinity which were compared with other two kinds of HAM. HAM by the NAHAs showed some hollow and burst open structural and has lower crystallinity. HAM by the IWHAs has the porous structure, larger particle size range and lowest crystallinity (29.8%). In addition, the specific surface area (167.16 m2/g) and the total pore volume (0.5054 ml/g) of HAM by the IWHAs were much higher than that of HAM by AHAs (52.523 m2/g and 0.2331 ml/g, respectively).
Because the characteristic of HA slurry can significantly impact the properties of HAM by the flame-drying method, it is necessary to research the crystal process during procedure of synthesis HA. The results showed that HA crystallization and its crystal grain microstructure in the slurry were affected by the reaction time and temperature as well as sedimentation time. Among them, the reaction temperature is the main parameters of crystalline HA. High temperature could provide more free energy, so that HA crystallinity increased with the temperature increasing.
The TEM microstructure of HAM by the flame-drying method showed that the properties of HA crystal in the original slurry would affect the HAM microstructure. The component particles of HAM by the NAHAs had the high crystallinity, and distributed as rod or strip like. For the HAM by AHAs, there were some non-transparent crystal existents in the microstructure morphologies. The TEM results indicated that some bubble-like defects were existed in the nano-particles of HAM by the IWHAs. In addition, there were lots of nano-pores included in the HAM by the IWHAs, which resulted in its soft microstructure.
Three kinds of HAM by the flame-drying method showed different impacts at different calcining temperature. A little change took place on the surface morphologies, crystallinity and BET of HAM after sintering under 600℃. The grain of HAM became coarsening and fusion with the calcining temperature increasing above 800℃. Moreover, impure phases, such asα-TCP andβ-TCP, appeared when HA decomposed at 1000℃. And the BET and porosity of HAM were significantly decreased because small particles united together when calcined at higher temperature. However, for HAM by the IWHAs, obviously changes appeared, including the BET and total pore volume markedly decreased, even though at lower calcining temperature.
In vitro experiment indicated that HAM fabricated by the flame-drying method has the good bioactivity and the potential application of adsorption and control release for bovine serum albumin (BSA). Three kinds of HAM showed different impacts in the physiological environment. Among them, the HAM by the IWHAs had the best bioactivity because of its lowest crystallinity and high total pore volume. In vivo data showed that HAM by the flame-drying method had non-toxic effect and could be well integrate with bone. Histology results demonstrated that the HAM had well osteoconduction and biodegradation after implanting into New Zealand rabbit femur for 4 months. The degradability of HAM by the IWHAs was much more serious compared with the other two kinds of HAM. In addition, SEM morphologies showed that some connective tissue grew into the HAM implants after implanting into rabbit's femur for 4 months.
Polymer combined with HAM could form composite biomaterials which would modify the acidic environment due to degradability of HA and improve biological and mechanical properties. In this study, porous PLLA/HAM composite scaffolds were fabricated by the thermally induced phase separation technology. The results demonstrated that the HAM was uniformly incorporated into the PLLA/HAM composite porous scaffolds. As the HAM ratio was increased the porous composite scaffolds changed from ladder-like into isotropic structure. In addition, the mechanical property of PLLA/HAM composite scaffolds improved with increasing HAM ratio in the scaffolds. The compressive modulus reached to maximum (9.1MPa) when the HAM ratio was 30% in the composite scaffolds. While the compressive of plain PLLA scaffolds was only 4.4MPa. Bone-like apatites would be formed onto the surface of composite scaffolds after incubated into simulated body fluid (SBF) for a period of time. And the amount of deposition on the surface of scaffolds was increased with the HAM ratio increasing. Meanwhile, BSA adsorption of composite scaffolds was also improved as adding into HAM.
In vitro experiment indicated that PLLA/HAM composite scaffolds improved the attachment, migration and differentiation of MC3T3 osteoblastic cells after culture for 4 weeks. It demonstrated that the PLLA/HAM composite scaffolds were superior to plain PLLA scaffold for bone tissue engineering. The histologies morphologies also showed that the cells could grow into and well integrate with PLLA/HAM composite scaffolds.
本文利用自制的火焰-喷雾干燥装置,以高于500℃的甲烷火焰为干燥介质,通过调整原始HA料浆的参数,得到结晶度较低、孔隙度较高的HA微球。利用扫描电子显微镜(SEM)、透射电子显微镜(TEM)、高分辨透射电镜(HRTEM)、场发射电子显微镜(FE-SEM)、X射线衍射仪(XRD)、比表面积分析仪(SSA)、激光粒度分析仪(LDPSA)、红外光谱分析仪(FTIR)等检测手段,对所得HA微球的形貌、相组成、粒度分布、比表面积、孔径分布、微观结构特征以及基团分布等进行了系统的分析研究,优化出了利用火焰-雾化干燥法制备HA微球的工艺参数。以去氨水处理后的料浆、未去氨水料浆和冰水混合物料浆为试验对象,对采用火焰-雾化干燥法制备出的三种HA微球进行体外、体内试验,研究不同结晶度和结构形态的HA微球在生物学行为上的差异。进而以未去氨水料浆火焰干燥所得的HA微球为例,利用热致相分离技术制备多孔PLLA/HA微球复合支架,系统研究了不同比例的HA微球对复合支架力学性能和生物学性能的影响。
结果表明,利用自制的火焰-喷雾干燥装置,在甲烷火焰高温干燥介质中得到的HA微球,能更多的保留HA在原料浆中的性质。原始料浆中的氨水在干燥过程中分解的氨气气体会导致HA微球结构疏松,比表面积增加,粒度分布不均。低温原始料浆干燥后,可得到低结晶度、结构疏松且粒度不均的HA微球。本试验中,冰水混合物料浆所得HA微球的结晶度为29.8%,远低于典型HA颗粒90%以上的结晶程度,且比表面积(167.16 m2/g)和总孔体积(0.5054ml/g)远高于去氨水处理后料浆所得微球(52.523 m2/g,0.2331 ml/g)。本研究可以通过调节HA料浆的参数来降低所得HA微球的结晶度,改善其结构和性能。
HA料浆的性质对火焰干燥后所得HA微球的性能有重要影响。HA在其料浆中的结晶程度和晶粒微观形貌受反应时间、沉化时间以及反应温度等因素的影响。在常温条件下,随反应时间的延长,HA的结晶程度越来越高。料浆沉化一段时间后,其中的HA纳米晶体呈针状生长。反应温度越高料浆中HA的结晶度越高。
火焰-雾化干燥HA微球的结晶程度随原始料浆中HA的结晶度升高而增加。TEM结果表明,组成去氨水料浆所得的HA微球的微颗粒呈棒状或条状分布；未去氨水料浆所得HA微球中有部分非透明的非晶存在；而冰水混合物料浆所得HA微球的晶粒存在泡状半透明球状非晶磷酸钙。另外,冰水混合物料浆所得HA微球表面存在较多疏松的微孔结构。
煅烧温度对不同性质HA料浆所得HA微球的影响程度也不相同。中低温处理(低于600℃)对去氨水处理后的料浆所得HA微球的形貌、结晶度以及比表面积没有明显影响。高温煅烧处理(800℃-1000℃)会使微球的晶粒粗化长大,并在微球内部熔合,进而明显降低其比表面积和孔体积。但是600℃低温煅烧后,冰水混合物料浆所得的微球比表面积和孔体积也会从原来的167.16m2/g,0.5054 ml/g分别急剧降至65.985 m2/g和0.1952 ml/g。
火焰干燥所得HA微球在体外生物模拟实验中的结果表明其具有较好的生物活性,并对BSA蛋白质有一定的吸附和缓释作用。SBF浸泡后HA微球的质量变化呈先减小后增加的趋势。HA微球结晶度越低,质量变化越明显。HA微球对BSA的吸附量并不是单纯地随结晶度的降低而升高,还受孔隙度和降解速率的影响。在体内生物体液作用一段时间后,火焰-雾化干燥后的HA微球无毒副作用,并和活体骨结合良好。从组织形貌分析来看,HA微球植入体具有良好的骨引导能力。植入新西兰大白兔的股骨中4个月后,三种植入体周围都形成了新的生物组织,且有不同程度的降解,降解程度随结晶度的降低而增加；未去氨水料浆所对应的HA微球植入体内部有结缔组织长入。
HA微球加入到高分子材料中能形成复合生物材料,改善高分子材料由于降解而产生的酸性环境,提高复合材料的生物学性能和力学性能。本研究将未去氨水料浆经火焰-雾化干燥法所得HA微球均匀的混入PLLA的二氧六环溶液中,利用热致相分离技术成功制备出连通度较好的多孔PLLA/HA微球复合支架。结果表明,HA微球和PLLA材料能较好的结合,且随着HA微球加入量的增加,复合支架结构的不规则程度加剧,力学性能提高。相对于纯PLLA多孔支架的压缩模量(4.4MPa),HA微球的质量比占复合支架的30%时,复合支架的压缩模量(9.1MPa)最高。在SBF中浸泡一段时间后,支架表面会形成类骨磷灰石,并且其沉积量随HA微球含量的增加而增加。同时,HA微球的加入还能提高复合支架对BSA蛋白质的吸附能力。
大鼠的MC3T3成骨细胞4周的培养后,在PLLA/HA微球复合支架上能较好的粘附、分化和繁殖。由于HA微球具有优异的生物活性和良好的润湿性,加入后能使细胞更好的在复合支架材料上分化和繁殖。组织学切片也表明,PLLA/HA微球复合支架中的部分细胞能够长入到支架内部,和材料融合状态良好。
Hydroxyapatite (HA) can be widely used for repair and replacement of damaged or traumatized bone tissues due to its good biocompatibility and bioactivity. With specific porous structure and good surface properties, spherical HA has been potentially applied on the field of separation and purification for bioactivity macromolecules, such as proteins, nucleic acids and enzymes. The lower crystallinity or amorphous HA microspheres (HAM) has broad application prospect not only because of its good flowability and high specific surface area, but also its biodegradable and excellent bioactivity. One of method reducing the crystallinity of HAM is through changing the properties of HA slurries and rapid solidification, which can retain much more characteristic of original HA slurry in the HAM. The low crystallinity HAM can be used for drug delivery, cell culture carrier, bone filter, bone repair and other fields because of its good properties. So far, hollow and porous HAM mainly has been fabricated primarily by the template method and then calcinated it. However, almost no degradable HAM with high crystallinity could be prepared using this mehod. The relevant reports about preparation and characterization of lower crystallinity of HAM are very rare.
In this study, HAM with low crystallinity and high porosity were fabricated by the flame-drying method with self-made device using methane flame as the drying medium. The microstructure, phase component and other performances of HAM were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), transmission electron microscopy (TEM), laser diffraction particle size analyzer (LDPSA), surface area analyzer (SSA), and fourier transform infrared spectrum analyzer (FTIR). Besides, the parameters of the flame-drying method were systematically optimized in the process of HAM fabrication. Three kinds of HAM were fabricated by that flame-drying method using HA slurries with ammonia (AHAs), without ammonia (NAHAs) and under ice-water condition (IWHAs), respectively. The in vitro and vivo experiments of HAM were discussed for studying the biological behavior differences with different crystallinity and microstructure. Furthermore, taking the HAM by the NAHAs as the supplement, porous PLLA/HAM composite scaffolds were fabricated by the thermally induced phase separation technology. Then the effect of content of HAM in the composite scaffolds on their mechanical and biological properties was systematically researched in this paper.
The results indicated that HAM has been retained more performances of HA crystal in the slurry under higher drying medium using self-made flame-drying device. According to these results, it could reduce the crystallinity of HAM and improve its structural properties through changing HA slurries parameters. In this paper, HAM by the AHAs has the regular spherical structure, smooth surface morphology, smaller particle size range and highest crystallinity which were compared with other two kinds of HAM. HAM by the NAHAs showed some hollow and burst open structural and has lower crystallinity. HAM by the IWHAs has the porous structure, larger particle size range and lowest crystallinity (29.8%). In addition, the specific surface area (167.16 m2/g) and the total pore volume (0.5054 ml/g) of HAM by the IWHAs were much higher than that of HAM by AHAs (52.523 m2/g and 0.2331 ml/g, respectively).
Because the characteristic of HA slurry can significantly impact the properties of HAM by the flame-drying method, it is necessary to research the crystal process during procedure of synthesis HA. The results showed that HA crystallization and its crystal grain microstructure in the slurry were affected by the reaction time and temperature as well as sedimentation time. Among them, the reaction temperature is the main parameters of crystalline HA. High temperature could provide more free energy, so that HA crystallinity increased with the temperature increasing.
The TEM microstructure of HAM by the flame-drying method showed that the properties of HA crystal in the original slurry would affect the HAM microstructure. The component particles of HAM by the NAHAs had the high crystallinity, and distributed as rod or strip like. For the HAM by AHAs, there were some non-transparent crystal existents in the microstructure morphologies. The TEM results indicated that some bubble-like defects were existed in the nano-particles of HAM by the IWHAs. In addition, there were lots of nano-pores included in the HAM by the IWHAs, which resulted in its soft microstructure.
Three kinds of HAM by the flame-drying method showed different impacts at different calcining temperature. A little change took place on the surface morphologies, crystallinity and BET of HAM after sintering under 600℃. The grain of HAM became coarsening and fusion with the calcining temperature increasing above 800℃. Moreover, impure phases, such asα-TCP andβ-TCP, appeared when HA decomposed at 1000℃. And the BET and porosity of HAM were significantly decreased because small particles united together when calcined at higher temperature. However, for HAM by the IWHAs, obviously changes appeared, including the BET and total pore volume markedly decreased, even though at lower calcining temperature.
In vitro experiment indicated that HAM fabricated by the flame-drying method has the good bioactivity and the potential application of adsorption and control release for bovine serum albumin (BSA). Three kinds of HAM showed different impacts in the physiological environment. Among them, the HAM by the IWHAs had the best bioactivity because of its lowest crystallinity and high total pore volume. In vivo data showed that HAM by the flame-drying method had non-toxic effect and could be well integrate with bone. Histology results demonstrated that the HAM had well osteoconduction and biodegradation after implanting into New Zealand rabbit femur for 4 months. The degradability of HAM by the IWHAs was much more serious compared with the other two kinds of HAM. In addition, SEM morphologies showed that some connective tissue grew into the HAM implants after implanting into rabbit's femur for 4 months.
Polymer combined with HAM could form composite biomaterials which would modify the acidic environment due to degradability of HA and improve biological and mechanical properties. In this study, porous PLLA/HAM composite scaffolds were fabricated by the thermally induced phase separation technology. The results demonstrated that the HAM was uniformly incorporated into the PLLA/HAM composite porous scaffolds. As the HAM ratio was increased the porous composite scaffolds changed from ladder-like into isotropic structure. In addition, the mechanical property of PLLA/HAM composite scaffolds improved with increasing HAM ratio in the scaffolds. The compressive modulus reached to maximum (9.1MPa) when the HAM ratio was 30% in the composite scaffolds. While the compressive of plain PLLA scaffolds was only 4.4MPa. Bone-like apatites would be formed onto the surface of composite scaffolds after incubated into simulated body fluid (SBF) for a period of time. And the amount of deposition on the surface of scaffolds was increased with the HAM ratio increasing. Meanwhile, BSA adsorption of composite scaffolds was also improved as adding into HAM.
In vitro experiment indicated that PLLA/HAM composite scaffolds improved the attachment, migration and differentiation of MC3T3 osteoblastic cells after culture for 4 weeks. It demonstrated that the PLLA/HAM composite scaffolds were superior to plain PLLA scaffold for bone tissue engineering. The histologies morphologies also showed that the cells could grow into and well integrate with PLLA/HAM composite scaffolds.
引文
1 余耀庭,张兴栋.生物医用材料[M].天津：天津大学出版社,2000,1-2.
2 Williams DF. On the nature of biomaterials [J]. Biomaterials,2009,30:5897-5909.
3 崔福斋,冯庆玲.生物材料学[M].北京：清华大学出版社,2004,1-2.
4 谈国强,苗鸿雁,宁青菊,夏傲.生物陶瓷材料[M].北京：化学工业出版社,2006,1-2.
5 Bres EF, Moebus G, Kleebe JJ, Pourry G, Wekmann J, Ehret G.. High resolution electron microscopy study of amorphous calcium phosphate [J]. Journal of Crystal Growth,1993, 129:149-162.
6 Hench LL. Biomaterials:a forecast for the future [J]. Biomaterials,1998,19:1419-1423.
7 Horlington M. Biomaterials:present and future [J]. Materials World,1995,3:332-333.
8 Vallet-Regi M, Gonzalez-Calbet JM. Calcium phosphates as substitution of bone tissues [J]. Progress in Solid States Chemistry,2004,32:1-31.
9 Wopenka B, Pasteris JD. A mineralogical perspective on the apatite in bone [J]. Materials Science and Engineering C,2005,25:131-143.
10 Zakharov NA, Polunina IA, Polunin KE, Rakitina NM, Kochetkova El, Sokolova NP, Kalinnikov VT. Calcium hydroxyapatite for medical applications [J]. Inorganic Materials, 2004,40:641-648.
11 Ginebra MP, Traykova T, Planell JA. Calcium phosphate cements:Competitive drug carriers for the musculoskeletal system [J]. Biomaterials,2006,27:2171-2177.
12 Rauschmann MA, Wichelhaus TA, Stirnal V, Dingeldein E, Zichner L, Schnettler R, Alt V. Nanocrystalline hydroxyapatite and calcium sulphate as biodegradable composite carrier material for local delivery of antibiotics in bone infections [J]. Biomaterials,2005,26: 2677-2684.
13 Madhavi S, Ferraris C, White TJ. Synthesis and crystallization of macroporous hydroxyapatite [J]. Journal of Solid State Chemistry,2005,178:2838-2845.
14刘国诠.生物工程下游技术[M].北京：化学工业出版社,2003,265-276.
15 Castner DG, Ratner BD. Biomedical surface science:Foundations to frontiers [J]. Surface Science,2002,500:28-60.
16 Komlev VS, Barinov SM, Koplik EV. A method to fabricate porous spherical hydroxyapatite granules intended for time-controlled drug release [J]. Biomaterials,2002, 23:3449-3454.
17 Jungbauer A, Hahn R, Deinhofer K, Luo P. Performance and characterization of a nanophased porous hydroxyapatite for protein chromatography [J]. Biotechnology and Bioengineering,2004,87:364-375.
18 Suchanek W, Yoshimura M. Processing and properties of hydroxyapatite-based biomaterials for use as hard tissue replacement implants [J]. Journal of Materials Research,1998,13:94-117.
19 Ito A, Nakamura S, Aoki H, Teraoka K, Onuma K, Tateishi T. Hydrothermal growth of carbonate-containing hydroxyapatite single crystals [J]. Journal of Crystal Growth,1996, 163:311-317.
20李新化,郑治祥,汤文明,吕君,刘君武.羟基磷灰石生物陶瓷材料的现状及展望[J].合肥工业大学学报,2002,25：1148-1153.
21 Lopes MA, Knowles JC, Santos JD. Structural insights of glass-reinforced hydroxyapatite composites by rietveld refinement [J]. Biomaterials,2000,21:1905-1910.
22 Leventouri Th. Synthetic and biological hydroxyapatites:Crystal structure questions [J]. Biomaterials,2006,27:3339-3342.
23 Yasushi S, Junzo T. Crystal growth and structure analysis of twin-free monoclinic hydroxyapatite [J]. Journal of Materials Science:Materials in Medicine,2002,13: 767-772.
24 Kay MI, Young RA, Posner AS. Crystal structure of hydroxyapatite [J]. Nature,1964,204: 1050-1052.
25 Weiner S, Wagner HD. Material bone:structure-mechanical function relations [J]. Annual Review of Materials Science,1998,28:271-98.
26 Dorozhkin SV. Calcium orthophosphates in nature, biology and medicine [J]. Materials, 2009,2:399-498.
27 Davies JE. In vitro modeling of the bone/implant interface [J]. Anatomical Record-Advances in Integrative Anatomy and Evolutionary Biology,1996,245:426-445.
28 Anselme K. Osteoblast adhesion on biomaterials [J]. Biomaterials,2000,21:667-681.
29 Sergey V. Dorozhkin. Bioceramics of calcium orthophosphates [J]. Biomaterials,2010,31: 1465-1485.
30李世普.生物医用材料导论[M].武汉：武汉工业大学出版社,2000,84-95.
31 Yuan HP, Kurashina K, de Bruijn JD, Li YB, de Groot K, Zhang XD. A preliminary study on osteoinduction of two kinds of calcium phosphate ceramics [J]. Biomaterials,1999,20: 1799-1806.
32 Zheng XB, Huang MH, Ding CX. Bond strength of plasma-sprayed hydroxyapatite/Ti composite coatings [J]. Biomaterials,2000,21:841-849.
33储成林,朱景川,尹钟大,王世栋.羟基磷灰石(HA)生物复合材料的研究进展[J].材料导报,1999,13：51-54.
34 Chiba A, Sahakura S, Kobayashi K, Kusayanagi K. Dissolution amounts of nickel, chromium and iron from SUS 304,316 and 444 stainless steels in sodium chloride solution[J]. Journal of Materials Science,1997,32:1995-2000.
35顾其胜,侯春林,徐政.实用生物医用材料学[M].上海：上海科学技术出版社,2005,9：106-107.
36 Chen YM, Lu YP, Li MS. Surface changes of plasma-sprayed hydroxyapatite coatings before and after heat treatment [J]. Surface Engineering,2006,22:462-467.
37 Ding SJ, Su YM, Ju CP, Lin JHC. Structure and immersion behaviour of plasma sprayed apatite-matrix coatings [J]. Biomaterials,2001,22:833-845.
38 Xiao GY, Lu YP, Zhu RF, Xu WH, et al. Effect of heat-treatment on the performance of hydroxyapatite coatings immersed in SBF [J]. Surface Engineering,2009,25:136-140.
39 Xiao GY, Lu YP, Zhu RF, Li ST, Wang AJ. Effect of post-heat treatment on inner planar microstructure and mechanical performance of hydroxyapatite coating [J]. Surface Engineering,2008,24:307-312.
40 Gotfredsen Klaus, Wennerberg Ann, Johansson Carina, Skovgaard Lene Teil, Hjorting-Hansen Erik. Anchorage of TiO2-blasted, HA-coated, and machined implants:an experimental study with rabbits [J]. Journal of Biomedical Materials Research,1995,29 10:1223-1231.
41 Weng J, Liu XG, Zhang XD, Ma Z, Ji X, Zyman Z. Further studies on the plasma-sprayed amorphous phase in hydroxyapatite coatings and its deamorphization [J]. Biomaterials, 1993,14:578-582.
42 Jin HH, Lee CH, Lee WK, Lee JK, Park HC, Yoon SY. In-situ formation of the hydroxyapatite/chitosan-alginate composite scaffolds [J]. Mareials Letters,2008,62, 1630-1633.
43 Sanchez-Salcedo S, Nieto A, Vallet-Regi M. Hydroxyapatite/β-tricalcium phosphate/agarose macroporous scaffolds for bone tissue engineering [J]. Chemical Engineering Journal,2008,137,62-71.
44 Liu XH, Laura A, Smith, Hu J, Ma PX. Biomimetic nanofibrous gelatin/apatite composite scaffolds for bone tissue engineering [J]. Biomaterials,2009,30:2252-2258.
45 Uhrich KE, Cannizzaro SM, Langer RS, Shakesheff KM. Polymeric systems for controlled drug release [J]. Chemical Reviews,1999,99:3181-3198.
46 Zhang JX, Ma PX. Polymeric Core-Shell Assemblies Mediated by Host-Guest Interactions: Versatile Nanocarriers for Drug Delivery [J]. Angewandte Chemie International Edition, 2009,48:964-968.
47 Zhang JX, Sun HL, Ma PX. Host-Guest Interaction Mediated Polymeric Assemblies: Multifunctional Nanoparticles for Drug and Gene Delivery [J]. Acs Nano,2010,4: 1049-1059.
48 Almirall A, Larrecq G, Delgado JAA. Fabrication of low temperature macroporous hydroxyapatite scaffolds by foaming and hydrolysis of an alpha-TCP paste [J]. Biomaterials,2004,17:3671-3680.
49 Barralet JE, Lilley KJ, Grover LM, Farrar DF, Ansell C, Gburecka U. Cements from nanocrystalline hydroxyapatite [J]. Journal of Materials Science:Materials in Medicine, 2004,15:407-411.
50 Queiroz AC, Santos JD, Monteiro FJ. Porous HA scaffolds for drug releasing [J]. Bioceramics,2005,17:407-410.
51 Rauschmann MA, Wichelhaus TA, Stirnal V, Dingeldein E, Zichner L, Schnettler R, et al. Nanocrystalline hydroxyapatite and calcium sulphate as biodegradable composite carrier material for local delivery of antibiotics in bone infections [J]. Biomaterials,2005,26: 2677-2684.
52 Yang HH, Zhu QZ, Qu HY, Chen XL, Din MT, Xu JG. Flow injection fluorescence immunoassay for gentamicin using sol-gel derived mesoporous biomaterial [J]. Analytical Biochemistry,2002,308:71-76.
53 Caliceri P, Salmaso S, Lante A, Yoshida M, Katakai R, Martellini F, et al. Controlled release of biomolecules from temperature-sensitive hydrogels prepared by radiation polymerization [J]. Journal of Controlled Release,2001,75:173-181.
54 Changez M, Burugapalli K, Koul V, Choudhary V. The effect of composition of poly (acrylic acid)-gelatin hydrogel on gentamicin sulphate release:in vitro [J]. Biomaterials, 2003,24:527-536.
55 Zhu YF, Shi JL, Shen WH, Dong XP, Feng JW, Ruan ML, et al. Stimuli-responsive controlled drug release froma hollow mesoporous silica sphere/polyelectrolyte multilayer core-shell structure [J]. Angewandte Chemie International Edition,2005,44:5083-5087.
56 Fu Q, Rama Rao GV, Ista LK, Wu Y, Andrzejewski BP, Sklar LA, et al. Control of molecular transport through stimuli-responsive ordered mesoporous materials [J]. Advanced Materials,2003,15:1262-1266.
57 Andersson J, Rosenholm J, Areva S, Linde'n M. Influences of material characteristics on ibuprofen drug loading and release profiles from ordered microand mesoporous silica matrices [J]. Chemistry of Materials,2004,16:4160-4167.
58 Zhou J, Wu W, Caruntu D, Yu MH, Martin A, Chen JF, et al. Synthesis of porous magnetic hollow silica nanospheres for nanomedicine application [J]. Journal of Physical Chemistry C,2007,111:17473-17477.
59 Barroug A, Kuhn LT, Gerstenfeld LC, Glimcher MJ. Interactions of cisplatin with calcium phosphate nanoparticles:in vitro controlled adsorption and release [J]. Journal of orthopaedic research,2004,22:703-708.
60 Stigter M, De Groot K, Layrolle P. Incorporation of tobramycin into biomimetic hydroxyapatite coating on titanium [J]. Biomaterials,2002,23:4143-4153.
61 Del Real RP, Padilla S, Vallet-Regi M. Gentamicin release from hydroxyapatite/poly (ethyl methacrylate)/poly (methyl methacrylate) composites [J]. Journal of Biomedical Materials Research Part A,2000,52:1-7.
62 Sivakumar M, Panduranga Rao K. Preparation, characterization and in vitro release of gentamicin from coralline hydroxyapatite-alginate composite microspheres [J]. Journal of Biomedical Materials Research Part A,2003,65:222-228.
63 Sivakumar M, Manjubala I, Panduranga Rao K. Preparation, characterization and in vitro release of gentamicin from coralline hydroxyapatite-chitosan composite microspheres [J]. Carbohydrate Polymers,2002,49:281-288.
64 Barroug A, Glimcher MJ. Hydroxyapatite crystals as a local delivery system for cisplatin: absorption and release of cisplatin in vitro [J]. Journal of orthopaedic research,2002,20: 274-280.
65 Paul W, Sharma CP. Development of porous spherical hydroxyapatite granules:application towards protein delivery [J]. Journal of Materials Science:Materials in Medicine,1999, 10:383-388.
66孙瑞雪.多孔及空心羟基磷灰石微球的制备与表征[D].山东大学博士毕业论文,2007，06.
67 Yang Piaoping, Wuan Zewei, Li Chunxia, Kang Xiaojiao, Lian Hongzhou, Lin Jun. Bioactive, Luminescent and mesoporous europium-doped hydroxyapatite as a drug carrier [J]. Biomaterials,2008,29:4341-4347.
68李校望.药物蛋白质分离纯化技术[M].北京：化学工业出版社,2004,1：157-158.
69余晓英,周纯益,余贤真,欧阳藩.新型、高效球形羟基磷灰石分离介质[J].生物工程进展,1996,16：17.
70 Shepard SR, Stone CB, Schrimsher JL, Koch G. Discoloration of ceramic hydroxyapatite used for protein chromatography [J]. Journal of Chromatography A,2000,891:93.
71王爱娟.羟基磷灰石微球分离介质的制备与结构和性能分析[D].山东大学博士毕业论文,2009,06.
72 Paul W, Sharma CP. Modified hydroxyapatite microsphere as immunoadsorbent for plasma perfusion:preliminary study [J]. Journal of Colloid and Interface Science,1995,174: 224-229.
73 Barroug A., Fastrez J., Lemattre J., Rouxhet P.. Adsorption of succinylated lysozyme on hydroxyapatite [J]. Journal of Colloid and Interface Science,1997,189:37-42.
74 Eis C, Griessler R, Maier M, Weinhausel A. Efficient downstream processing of maltodextrin phosphorylase from escherichia and stabilization of the enzyme by immobilization onto hydroxyapatite [J]. Journal of Biotechnology,1997,58:157-166.
75陈向东,吴梧桐,高向东,吕树军,张奉国,吕正兵.卡介菌多糖的分离纯化与药效研究[J].中国天然药物,2003,1：173-177.
76 Ford CHJ, Osborne PO, Mathew A, Rego BG. Affinity purification of novel bispecific antibodies recognizing carcinoembryonic antigen and doxorubicin [J]. Journal of Chromatography B,2001,754:427-435.
77 Herve F, Fouache F, Marche C, Tillement J P. Abnormal microheterogeneity detected in one commercial a 1-acid glycoprotein preparation using chromatography on immobilized metal affinity adsorbent and on hydroxyapatite [J]. Journal of Chromatography B,1997, 688:35-46.
78 Steen S, Steen JJ, Anders HJ. Purification and characterization of osteopontin from human milk [J]. Protein Expression and Purification,2003,30:238-245.
79 Lai H, Franklin SG. Purification of Murine IgGl using UNO sphere S and CHT Ceramic hydroxyapatite chromatography [J]. Bio-Rad Laboratories, tech note 2780. http://www. bio-rad.com.
80 Ordunez C, Franklin S G. Purification of horse IgGT using macro-prep DEAE and CHT Ceramic hydroxy-apatite type I supports [J]. Bio-Rad Laboratories, tech note 2524. http://www. bio-rad.com.
81 Meijer AG, Segenhout HM, Albers FW, et al. Histopathology of biocompatible hydroxyapatite-polyehylene composite in ossiculoplasty [J]. ORL J Otorhinolaryngol Related Specialties,2002,64:173-179.
82 Moursi AM, Winnard AV, Winnard PL, et al. Enhanced osteoblast response to a polymethylmethacrylate-hydroxyapatite composite [J]. Biomaterials,2002,23:133-144.
83 Salih V, Georgiou G, Knowles JC, et al. Glass reinforced hydroxyapatite for hard tissue surgery-part Ⅱ:in vitro evalution of bone cell growth and function [J]. Biomaterials, 2001,22:2817-2825.
84 Zhang Y, Ni M, Zhang M, et al. calcium phosphate-chitosan composite scaffolds for bone tissue engineering [J]. Tissue engineering,2003,9:337-342.
85 Zhang Y, Zhang M. Calcium phosphate/chitosan composite scaffolds for controlled in vitro antibiotic drug release [J]. Journal of Biomedical Materials Research,2002,62: 378-386.
86 Zhao F, Yin Y, Lu WW, et al. Preparation and histological evaluation of biomimetic three-dimensional hydroxyapatite/chitosan-gelatin network composite scaffolds [J]. Bioamtierials,2002,23:3227-3234.
87 Zhang RY, Ma PX. Biomimetic polymer/apatite composite scaffolds for mineralized tissue engineering [J]. Macromolecular Bioscience,2004,4:100-111.
88 Wei GB, Ma PX. Structure and properties of nano-hydroxyapatite/polymer composite scaffolds for bone tissue engineering [J]. Biomaterials,2004,25:4749-4757.
89 Niu XF, Feng QL, Wang MB, Guo XD, Zheng QX. Porous nano-HA/collagen/PLLA scaffold containing chitosan microspheres for controlled delivery of synthetic peptide derived from BMP-2 [J]. Journal of Controlled Release,2009,134:111-117.
90候小宝,谢田甜,刘志信,夏志军.羟基磷灰石的制备方法[P].中国发明专利,200410067736.7(2004).
91 Genin F. Luo YP, Dash AK. Hydroxyapatite based drug delivery implant for cancer treatment [P]. US Patent,6767550 (2004).
92 Troczynski T, Liu DM, Yang QZ. Biofunctional hydroxyapatite coatings and microspheres for in-situ drug encapsulation [P]. US Patent,6730324 (2004).
93 Fukue N, Tatsuya M, Yoshiyuki Y. A method to fabricate hydroxyapatite/poly(lactic acid) microspheres intended for biomedical application [J]. Journal of the European Ceramic Society,2006,26:533-553.
94 Sun RX, Lu YP, Li MS, Li ST, Zhu RF. Characterization of hydroxyapatite particles plasma-sprayed into water [J]. Surface and Coatings Technology,2005,190:281-286.
95 Sun RX, Chen KZ, Lu YP. Fabrication and dissolution behavior of hollow hydroxyapatite microspheres intended for controlled drug release [J]. Materials Research Bulletin,2009, 44:1939-1942.
96 Huang WH, Rahaman MN, Delbert ED, Brad AM. Strength of hollow hydroxyapatite microspheres prepared by a glass conversion process [J]. Journal of Materials Science: Materials in Medicine,2009,20:123-129.
97 Paul W, Nesamony J, Sharma CP. Delivery of insulin from hydroxyapatite ceramic microspheres:Preliminary in vivo studies [J]. Journal of Biomedical Materials Research Part A,2002,61:660-662.
98 Kweh SWK, Khor KA, Cheang P. The production and characterization of hydroxyapatite (HA) powders [J]. Journal of Materials Processing Technology,1999,89-90:373-377.
99 Keishiro T, Hidehiko A, Takatomo N, Kimiko M. Hydroxyapatite particles as drug carriers for proteins [J]. Colloids and Surfaces B:Biointerfaces,2010,76:226-235.
100 Lee HH, Hong SJ, Kim CH et al. Preparation of hydroxyapatite spheres with an internal cavity as a scaffold for hard tissue regeneration [J]. Journal of Materials Science: Materials in Medicine,2008,19:3029-3034.
101 Gao F, Su ZG, Wang P, Ma GH. Double emulsion templated microcapsules with single hollow cavities and thickness-controllable shells [J]. Langmuir,2009,25: 3832-3838.
102 Hong SJ, Yu HS, Kim HW. Tissue engineering polymeric microcarriers with macroporous morphology and bone-bioactive surface [J]. Macromolecular bioscience,2009,9: 639-645.
103 Lou XW, Archer A., Yang ZC. Hollow micr-/nanostructures:synthesis and applications [J]. Advanced materials,2008,20:3987-4019.
104 Caruso F, Caruso RA, Mohwald H. Nanoengineering of inorganic and hybrid hollow spheres by colloidal templating [J]. Science,1998,282:1111-1114.
105 Caruso, F. Nanoengineering of particle surfaces [J]. Advanced materials,2001,13:11-22.
106 Caruso F, Spasova M. Multilayer assemblies of silica-encapsulated gold nanoparticles on decomposable colloid templates[J]. Advanced materials,2001,13:1090-1094.
107 Valtchev V, Mintova S. Layer-by-layer preparation of zeolite coatings of nanosized crystals[J]. Microporous and Mesopouous Materials,2001,43:41-49.
108 Dyshlovenko S, Pawlowski L, Roussel P, Muranob D, Le Maguer A. Relationship between plasma spray operational parameters and microstructure of hydroxyapatite coatings and powder particles sprayed into water[J]. Surface and Coatings Technology, 2006,200:3845-3855.
109 Dyshlovenko S, Pateyron B, Pawlowski L, Murano D. Numerical simulation of hydroxyapatite powder behaviour in plasma jet [J]. Surface and Coatings Technology, 2004,179:110-117.
110 Bertling J, Blomer J, Kummel R. Hollow microspheres [J]. Chemical Engineering & Technology,2004,27:829-837.
111 Bertranda G, Roy P, Filiatre C, Coddet C. Spray-dried ceramic powders:Aquantitative correlation between slurry characteristics and shapes of the granules [J]. Chemical Engineering Science,2005,60:95-102.
112 Luo P, Nieh TG. Preparing hydroxyapatite powders with controlled morphology [J]. Biomaterials,1996,17:1959-1964.
113 Li GC, Zhang ZK. Synthesis of submicrometer-sized hollow titania spheres with controllable shells [J]. Materials Letters,2004,58:2768-2771.
114 Goula AM, Adamopoulos KG. Spray drying of tomato pulp in dehumidified air:Ⅱ The effect on powder properties [J]. Journal of Food Engineering,2005,66:35-42.
115 Goula AM, Adamopoulos KG. Spray drying of tomato pulp in dehumidified air:Ⅰ. The effect on product recovery [J]. Journal of Food Engineering,2005,66:25-34.
116 Apinan S, Fanny B, Hidefumi Y, Takeshi F, Masaaki O, Pekka L. Influence of emulsion and powder size on the stability of encapsulated d-limonene by spray drying [J]. Innovative Food Science and Emerging Technologies,2005,6:107-114.
117 Ma PX. Scaffold for tissue engineering [J]. Materials today,2004,5:30-40.
118 Kim HW, Song JH, Kim HE. Nanofiber generation of gelatin-hydroxyapatite biomimetics for guided tissue regeneration [J]. Advanced Functional Materials,2005,15:1988-1994.
119 Fujihara K, Kotaki M, Ramakrishna S. Guided bone regeneration membrane made of polycaprolactone/calcium carbonate composite nano-fibers [J]. Biomaterials,2005,26: 4139-4147.
120 Li C, Vepari C, Jin HJ, Kim H, Kaplan D. Electrospun silk-BMP-2 scaffolds for bone tissue engineering [J]. Biomaterials,2006,27:3115-3124.
121 Sui G, Yang X, Mei F, Hu X, Chen G, Deng X, et al. Poly-L-lactic acid/hydroxyapatite hybrid membrane for bone tissue regeneration [J]. Journal of Biomedical Materials Research, Part A 2007,82A:445-454.
122 Deng XL, Sui G, Zhao ML, Chen GQ, Yang XP. Poly(L-lactic acid)/hydroxyapatite hybrid nanofibrous scaffolds prepared by electrospinning [J]. Journal of Biomaterials Science:Polymer Edition,2007,18:117-130.
123 Catledge SA, Clem WC, Shrikishen N, Chowdhury S, Stanishevsky AV, Koopman M, et al. An electrospun triphasic nanofibrous scaffold for bone tissue engineering [J]. Journal of Biomedical Materials Research,2007,2:142-150.
124 Venugopal J, Vadgama P, Kumar TSS, Ramakrishna S. Biocomposite nanofibres and osteoblasts for bone tissue engineering [J]. Nanotechnology,2007,18:1-8.
125 Liu XH, Smith LA, Wei GB, Won YG, Ma PX. Surface engineering of nano-fibrous poly(L-Lactic acid) scaffolds via self-assembly technique for bone tissue engineering [J]. Journal of biomedical nanotechnology,2005,1:54-60.
126 Smith LA, Liu XH, Hu J, Ma PX. The influence of three-dimensional nanofibrous scaffolds on the osteogenic differentiation of embryonic stem cells [J]. Biomaterials, 2009,30:2516-2522.
127 Liu XH, Ma PX. Phase separation, pore structure, and properties of nanofibrous gelatin scaffolds [J]. Biomaterials,2009,30:4094-4103.
128 Ma PX, Zhang RY. Microtubular architecture of biodegradable polymer scaffolds [J] Journal of Biomedical Materials Research,2001,56,469-483.
1 Li YB, Wiliana T, Tam KC. Synthesis of amorphous calcium phosphate using various types of cyclodextrins [J]. Materials Research Bulletin,2007,42:820-827.
2 Zhang J, Gao X, Song BC, Wang ZF, Lu WW. A novel technique to synthesize hydroxyapatite whiskers[J]. Materials Letters,2008,62:1162-1164.
3 http://china.kytl.com/technology.aspx?cid=6&id=51
4 Tadashi Kokubo, Hiroaki Takadama. How useful is SBF in predicting in vivo bone bioactivity [J]? Biomaterials,2006,27:2907-2915.
5 Zhang RY, Ma PX. Poly(alpha-hydroxy acides)/hydroxyapatite porous composites for bone tissue engineering:1. Preaparation and morphology [J]. Journal of Biomedical Materials Research,1999,44:446-455.
6 Ma PX, Zhang RY, Xiao GZ, Franceschi R. Engineering new bone tissue in vitro on highly porous poly(alpha-hydroxyl acids)/hydroxyapatite composite scaffolds [J]. Journal of Biomedical Materials Research,2001,54:284-293.
7 Liu XH, Won YJ, Ma PX. Porogen-induced surface modification of nano-fibrous poly(L-lactic acid) scaffolds for tissue engineering [J]. Biomaterials,2006,27:3980-3987.
8 Xiao G, Cui Y, Ducy P, Karsenty G, Franceschi RT. Ascorbic acid-dependent activation of the osteocalcin promoter in MC3T3-E1 preosteoblasts:Requirement for collagen matrix synthesis and the presence of an intact OSE2 sequence [J]. Molecular Endocrinology,1997, 11:1103-1113.
9 Franceschi RT, Iyer BS. Relationship between collagen synthesis and expression of the osteoblast phenotype in MC3T3-E1 cells [J]. Journal of Bone and Mineral Research,1992, 7:235-246.
10 Schneider WC. Determination of nucleic acids in tissues by pentose analysis. Methods Enzymol,1957,3:680-684.
1 Luo P, Nieh TG. Preparing hydroxyapatite powders with controlled morphology [J]. Biomaterials,1996,17:1959-1964.
2 Luo P, Nieh TG. Synthesis of ultrafine hydroxyapatite particles by a spray dry method [J]. Materials Science and Engineering C,1995,3:75-78.
3 Bertranda G, Roya P, Filiatreb C, Coddeta C. Spray-dried ceramic powders:A quantitative correlation between slurry characteristics and shapes of the granules [J]. Chemical Engineering Science,2005,60:95-102.
4 Wang AJ, Lu YP, Sun RX. Recent progress on the fabrication of hollow microspheres [J]. Materials Science and Engineering A.2007,460-461:1-6.
5 李英霞,邹彪,田景振,周苏宁.喷雾干燥技术[J].山东中医杂志,2000,6：371-372.
6 王宝和,王喜忠.喷雾干燥技术的现状及展望[J].化工装备技术,1997,18：46-50.
7 黄立新,王宗濂,唐金鑫.我国喷雾干燥技术研究及进展[J].化学工程,2001,29：51-55.
8 张文孝,姚学勇,王玉德.喷雾干燥现状及展望[J].食品与机械,2004,20：33-35.
9 Wang AJ, Lu YP, Zhu RF, Li ST, Xiao GY, Zhao GF, Xu WH. Effect of sintering on porosity, phase and surface morphology of spray dried hydroxyapatite microspheres[J]. Journal of Biomedical Materials Research,2008,87A:557-562.
10孙瑞雪.多孔及空心羟基磷灰石微球的制备与表征[D].山东大学博士毕业论文,2007，06.
11王爱娟.羟基磷灰石微球分离介质的制备与结构和性能分析[D].山东大学博十毕业论文,2009,06.
12 Posner A, Betts SF. Synthetic amorphous calcium phosphate and its relation to bone mineral structure [J]. Accounts of Chemical Research,1975,8:273-281.
13 Dekker RJ, Van Blitterswijk CA, De Bruijn JD, Stigter M, Barrere F, Layrolle P.. Bone tissue engineering on amorphous carbonated apatite and crystalline octacalcium phosphate-coated titanium discs [J]. Biomaterials,2005,26:5231-5239.
14 Hakimimehr D, Liu DM, Troczynski T. In-situ preparation of poly(propylene fumarate)—hydroxyapatite composite. Biomaterials,2005,26:7297-7303.
15 Sun RX, Chen K.Z, Lu YP. Fabrication and dissolution behavior of hollow hydroxyapatite microspheres intended for controlled drug release [J]. Materials Research Bulletin,2009, 44:1939-1942.
16 Wang AJ, Lu YP, Zhu RF, Li ST, Xu WH. Effect of process parameters on the performance of spray dried HAM [J]. Powder technology,2009,191:1-6.
17 Sun R, Lu Y, Chen K. Preparation and characterization of hollow hydroxyapatite microspheres by spray drying method [J]. Materials science and engineering C,2009,29: 1088-1092.
18 Ferry I, Gradon L, Okuyama K. Control of the morphology of nanostructured particles prepared by the spray drying of a nanoparticle sol [J]. Journal of Colloid and Interface Science,2003,265:296-303.
19 Sun R, Li M, Lu Y, Wang A. Immersion behavior of hydroxyapatite (HA) powders before and after sintering [J]. Materials Characterization,2006:250-254.
20 Kweh SWK, Khor K A, Cheang P. The production and characterization of hydroxyapatite (HA) powders [J]. Journal of Materials Processing Technology,1999,89-90:373-377.
21 Patel N, Glbson I R, Ke S, Best S M, Bonfield W. Calcining influence on the powder properties of hydroxyapatite [J]. Journal of Materials Science:Materials in Medicine, 2001,12:181-188.
22 Sunny MC., Ramesh P, Varma HK. Microstructured microspheres of hydroxyapatite bioceramic[J]. Journal of Materials Science:Materials in Medicine,2002,13:623-632
23 Patel N, Gibson I Ke RS, Best SM, Bonfield W. Calcining influence on the powder properties of hydroxyapatite [J]. Journal of Materials Science:Materials in Medicine, 2001,12:181-188.
24 Raynaud S, Champion E, Bernache-Assollant D. Calcium phosphate apatites with variable Ca/P atomic ratio II. Calcination and sintering [J]. Biomaterials,2002,23:1073-1080.
25 Deepak K. Pattanayak, Rajalaxmi Dash, R.C. Prasad, B.T. Rao, T.R. Rama Mohan. Synthesis and sintered properties evaluation of calcium phosphate ceramics[J]. Materials Science and Engineering C,2007,27:684-690.
26 Senya I, Akira O, Nobuyuki O. Process for the preparation of microspherical sintered bodies of hydroxyapatite and a chromatographic packing material comprising the microspherical sintered bodies of hydroxyapatite [P]. US patent,5,205,928.
27郑月华,候小妹,杨兆雄.多孔HA生物陶瓷进展[J].硅酸盐通报.1995,3：20-24.
28史坚.现代柱色谱分析[M].上海：上海科学技术文献出版社.1988,7：104-106.
29石海涛.胰岛素-多孔羟基磷灰石微球口服给药系统的研究[D].四川大学博十学位论文.2005,11.
30 Bailliez S, Nzihou A. The kinetics of surface area reduction during isothermal sintering of hydroxyapatite adsorbent [J]. Chemical Engineering Journal,2004,98:141-152.
31 Caillet DA, Harrisson DP. Structural property variations in the MnO-MnS system [J], Chemical Engineering Science,1982,37:625-636.
32 Beckman-Coulter公司,COULTER-SA3100型表面积与孔隙分析仪说明书[M].
33 Raynaud S, Champion E, Bernache-Assollant D. Calcium phosphate apatites with variable Ca/P atomic ratio Ⅱ. Calcination and sintering [J]. Biomaterials,2002,23:1073-1080.
34 Sun R, Li M, Lu Y, An X. Effect of titanium and titania on chemical characteristics of hydroxyapatite plasma-sprayed into water [J]. Materials Science and Engineering C,2006, 26:28-33.
35 Tsui YC, Doyle C, Clyne TW. Plasma sprayed hydroxylapatite coatings on titanium substrates Part 2:optimization of coating properties [J]. Biomaterials,1998,19: 2031-2043.
36 Ding SJ, Huang TH, Kao CT. Immersion behavior of plasma-sprayed modified hydroxyapatite coatings after heat treatment [J]. Surface and Coatings Technology,2003, 165:248-257.
37 Tadic D, Peters F, Epple M. Continuous synthesis of amorphous carbonated apatites [J]. Biomaterials,2002,23:2553-2559.
38 Senya I, Akira O, Nobuyuki O. Process for the preparation of microspherical sintered bodies of hydroxyapatite and a chromatographic packing material comprising the microspherical sintered bodies of hydroxyapatite [P]. US patent,5,205,928 (1993).
39李明欧,肖秀峰,刘榕芳.含锌羟基磷灰石的水热合成与结构表征[J].硅酸盐学报,2008,36：378-382.
40 Joris SJ, Amberg CH. The nature of deficiency in non-stoichiometric hydroxyapatites [J]. The Journal of Physical Chemistry,1971,75:3172-3178.
41 Baddiel CB, Berry E. Spectra structure correlation in hydroxyl and fluorapatites [J]. Spectrochimica Acta Part A,1996,22:1407-1416.
42 Gonzalez-diaz PF, Santos M. On the hydroxyl ions in apatite [J]. Journal of Solid State Chemistry,1997,2:193-199.
43温喜梅,张军,宋邦才,马兰.水热条件下羟基磷灰石晶须的制备[J].中国陶瓷,2008，44：31-33.
44 Senamaud N, Bemache-Assollant D, Champion E, Heughebaert M, Rey C. Calcination and sintering of hydroxyfluorapatite powders[J]. Solid State Ionics,1997,101-103: 1357-1362.
45 Guo XY, Xiao P. Effects of solvents on properties of nanocrystalline hydroxyapatite produced from hydrothermal process [J]. Journal of the European Ceramic Society,2006, 26:3383-3391.
46 Lin F H, Li CJ, Chen KS, Sun JS. Thermal reconstruction behavior of the quenched hydroxyapatite powder during reheating in air [J]. Materials Science and Engineering C, 2000,13:97-104.
47 Nishikawa H. Thermal behavior of hydroxyapatite in structural and spectrophotometric characteristics [J]. Materials Letters,2001,50:364-370.
1 Rueger JM, Linhart W, Sommerfeldt D. Biological reactions to calcium phosphate ceramic implants. Results of animal experiments [J]. Orthop.ade,1998,27:89-95.
2 Stupp SI, Hanson JA,Eurell JA,Ciegler GW,Johnson A. Organoapatites:materials for artificial bone. III. Biological testing [J]. Journal of Biomedical Materials Research,1993, 27:301-311.
3 Du C, Cui FZ., Feng QL., Zhu XD, de Groot K. Tissue response to nano-hydroxyapatite/collagen composite implants in marrow cavity [J]. Journal of Biomedical Materials Research,1998,42:540-548.
4 Silver IA, Murrils RJ, Etherington DJ. Microelectrode studies on the acid microenvironment beneath adherent macrophages and osteoclast [J]. Experimental Cell Research,1988,175:266-276.
5 Vaes G. Cellular biology and biochemical mechanism of bone resorption [J]. Clinical Orthopaedics and Related Research,1988,231:239-271.
6 Teitelbaum SL, Tondravi MM, Ross FP. Osteoclasts, macrophages, and the molecular mechanisms of bone resorption [J]. Journal of Leukocyte Biology,1997,61:381-388.
7 Weiner S, Wagner HD. The material bone:structure-mechanical function relations [J]. Annual Review of Materials Research,1998,28:271-298.
8 Tadic D, Peters F, Epple M. Continuous synthesis of amorphous carbonated apatites [J]. Biomaterials,2002,23:2553-2559.
9 Doi Y, Shibutani T, Moriwaki Y, Kajimoto T, Iwayama Y. Sintered carbonate apatites as bioresorbable bone substitutes [J]. Journal of Biomedical Materials Research,1998,39: 603-610.
10 Shellis RP, Lee AR, Wilson RM. Observations on the apparent solubility of carbonate-apatites [J]. Journal of Colloid and Interface Science,1999,218:351-358.
11 Marion D. Francis. The inhibition of calcium hydroxyapatite crystal growth by polyphosphonates and polyphosphates [J]. Calcified Tissue International,1969,3: 151-162.
12 Suchanek W, Yoshimura M. Processing and properties of hydroxyapatite-based biomaterials for use as hard tissue replacement implants [J]. Journal of Materials Research,1998,13:94-117.
13余耀庭,张兴栋.生物医用材料[M].天津：天津大学出版社,2000：1-2.
14崔福斋,冯庆玲.生物材料学[M].北京：清华大学出版社,2004：1-2
15谈国强,苗鸿雁,宁青菊,夏傲.生物陶瓷材料[M].北京：化学工出版社,2006：1-2.
16 Viswanath B, Ravishankar N. Controlled synthesis of plate-shaped hydroxyapatite and implications for the morphology of the apatite phase in bone [J]. Biomaterials,2008,29: 4855-4863.
17 Li S, Xu J, Luo G. Control of crystal morphology through supersaturation ratio and mixing conditions [J]. Journal of Crystal Growth,2007,304:219-224.
18 Yang G, Kubota N, Sha Z, Louhi-Kultanen M, Wang J. Crystal shape control by manipulating supersaturation in batch cooling crystallization [J]. Crystal Growth & Design,2006,6:2799-2803.
19 Xin RL, Leng Y, Wang N. In situ TEM examinations of octacalcium phosphate to hydroxyapatite transformation [J]. Journal of Crystal Growth,2006,289:339-344.
20 Kim S, Ryu HS, Shin H, Jung HS, Hong KS. In situ observation of hydroxyapatite nanocrystal formation from amorphous calcium phosphate in calcium-rich solutions [J] Materials Chemistry and Physics,2005,91:500-506.
1 Kang YQ, Yao YD, Yin GF, Huang ZB, Liao XM, Xu XJ, Zhao GX. A study on the in vitro degradation properties of poly(1-lactic acid)/β-tricalcuim phosphate(PLLA/(3-TCP) scaffold under dynamic loading [J]. Europen Journal of Cardiovascular Prevention & Rehabilitation,2009,31:589-594
2 Kang YQ, Xu XJ, Yin GF, Chen AZ, Liao L, Yao YD, Huang ZB, Liao XM. A comparative study of the in vitro degradation of poly(1-1actic acid)/β-tricalcium phosphate scaffold in static and dynamic simulated body fluid [J]. European Polymer Journal,2007, 43:1768-1778.
3 邓春林.Ca-P生物陶瓷表面类骨磷灰石的形成、机理及其成骨性能研究[D].四川大学博士学位论文,2004,06.
4 Xiao GY, Lu YP, Zhu RF, Li ST, Wang AJ. Effect of post-deposition heat treatment on mechanical properties of thermally sprayed HA coating [J]. Surface Engineering,2008, 24:307-312.
5 Joseph NJ, Lakshmi S, Jayakrishnan A. A floating-type oral dosage form for piroxicam based on hollow polycarbonate microspheres:in vitro and in vivo evaluation in rabbits [J]. Journal of Controlled Release,2002,79:71-79.
6 Tadashi K, Hiroaki T. How useful is SBF in predicting in vivo bone bioactivity [J]? Biomaterials,2006,27:2907-2915.
7 段友容,姚喆,王朝元,陈继镛,张兴栋.多孔磷酸钙陶瓷在动态SBF中类骨磷灰石形成的研究[J].生物医学工程学杂志,2002,19：365-369.
8 Pierre L, Atsuo I, Tetsuya T. Sol-Gel Synthesis of Amorphous Calcium Phosphate and Sintering into Microporous Hydroxyapatite Bioceramics [J]. Journal of the American Ceramic Society,1998,81:1421-1428.
9 Suzanne HM, Joseph PZ, Michael GD. In vitro evaluation of amorphous calcium phosphate and poorly crystallized hydroxyapatite coatings on titanium implants [J]. Journal of Biomedical Materials Research,1993,27:111-117.
10 Masahisa N, Takashi N, Tadashi K, Masami T, Masaki O. Differences of bone bonding ability and degradation behaviour in vivo between amorphous calcium phosphate and highly crystalline hydroxyapatite coating [J]. Biomaterials,1996,17:1771-1777
11 Juhasz JA, Best SM, Auffret AD, Bonfield W. Biological control of apatite growth in simulated body fluid and human blood serum [J]. Journal of Materials Science:Materials in Medicine,2008,19:1823-1829.
12 Ugur T, Mustafa G. The effect of surface treatment on CaP deposition of Ti6Al4V open cell foams in SBF solution [J]. Ceramics International,2010,36:1805-1816.
13 Xiao GY, Lu YP, Zhu RF, Wang AJ. Effect of heat treatment on performance of hydroxyapatite coatings immersed in simulated body fluid [J]. Surface Engineering,2009, 25:136-140.
14孙瑞雪.多孔及空心羟基磷灰石微球的制备与表征[D].山东大学博士毕业论文,2006.
15 Mizushima Y, Ikoma T, Tanaka J, Hoshi K, Ishihara T, Ogawa Y, Ueno A. Injectable porous hydroxyapatite micropraticles as a new carrier for protein and lipophilic drugs [J]. Journal of Controlled Release,2006,110:260-265.
16 Kim HM, Himeno T, Kokubo T, Nakamura T. Process and kinetics of bonelike apatite formation on sintered hydroxyapatite in a simulated body fluid [J]. Biomaterials,2005,26: 4366-4373.
17李明欧,肖秀峰,刘榕芳.含锌羟基磷灰石的水热合成与结构表征[J].硅酸盐学报,2008，36：378-382.
18 Yu XH, Qu HB, Knech DAT, Wei M. Incorporation of bovine serum albumin ratio biomimetic coatings on titanium with high loading efficacy and its release behavior [J]. Journal of Materials Science:Materials in Medicine,2009,20:287-294.
19 Valeria M, Carlo C, Antonio E, Antonella G, Filippo P, Maurizio L. Aggregation kinetics of bovine serum albumin studied by FTIR spectroscopy and light scattering [J]. Biophysical Chemistry,2004,107:175-187.
20 Tatsuo M, Shinji K, Mitsutoshi N, Hiroshi N, Thomas PA, Atsushi S, Kazumi S. FT-IR analysis of BSA fouled on ultrafiltration and microfiltration membranes [J]. Journal of Membrane Science,2001,192:201-207.
21 Liu TY, Chen SY, Liu DM, Liou SC. On the study of BSA-loaded calcium-deficient hydroxyapatite nano-carriers for controlled drug delivery [J]. Journal of Controlled Release,2005,107:112-121.
22 Arvind S, Suprabha N, Archana A, Debasish B, Patcha R. Synthesis of Nanosized and Microporous Precipitated Hydroxyapatite in Synthetic Polymers and Biopolymers [J]. Journal of the American Ceramic Society,2003,86:357-359.
23刘艳.羟基磷灰石吸附有机物质的研究[D].济南大学硕士学位论文,2005,06.
24叶青.羟基磷灰石与牛血.清白蛋白相互作用的原位ATR-FTIR及EQCM研究[D].厦门大学硕士学位论文,2006,06.
25 Takagi O, Kuramoto N, Ozawa M, Suzuki S. Adsorption/desorption of acidic and basic proteins on needle-like hydroxyapatite filter prepared by slip casting [J]. Ceramics International,2004,30:139-143.
26 Yin G, Liu, Zhan J, Ding FX, Yuan NJ. Impacts of the surface charge property on protein adsorption on hydroxyapatite [J]. Chemical Engineering Journal,2002,87:181-186.
27 Kandori K, Fudo A, Ishikawa T. Study on the particle texture dependence of protein adsorption by using synthetic micrometer-sized calcium hydroxyapatite particles [J]. Colloids and Surfaces B:Biointerfaces,2002,24:145-153.
28 Ouizat S, Barroug1 A, Legrouri A, Rey C. Adsorption of bovine serum albumin on pooly crystalline apatite:influence of maturation [J]. Materials Research Bullitin,1999,34: 2279-2289.
29 Ogawa T, Yokoo A, Naganuma K, Fujinuma S, Kawamura K. Porous particles of calcium phosphate compound and production process thereof [P]. US Patent,5158756 (1990).
30 Liu YL, Hunziker EB, Layrolle P, De Bruijn JD, De Groot K. Bone Morphogenetic Protein 2 Incorporated into Biomimetic Coatings Retains Its Biological Activity [J]. Tissue Engineering,2004,10:101-108.
31 Luong NL, Sun IH, Patel RJ, Mark E. Outslay, David H. Kohn. Spatial control of protein within biomimetically nucleated mineral [J]. Biomaterials,2006,27:1175-1186.
32 Diana T. Hughes W, Rachel CH, Graham E. Adsorption of bovine serum albumin onto hydroxyapatite [J]. Biomaterials,1995,16:697-702.
33 Chou YF, Chiou WA, Xu YH, Dunn JCY, Wu BM. The effect of pH on the structural evolution of accelerated biomimetic apatite [J]. Biomaterials,2004,25:5323-5331.
34 Liu Y, De Groot K, Hunziker EB. Osteoinductive Implants:The Mise-en-scene for Drug-Bearing Biomimetic Coatings [J]. Annals of Biomedical Engineering,1994,32: 398-406.
35 Hing KA, Best SM, Tanner KE, Bonfield W, Revell PA. Quantification of bone ingrowth within bone-derived porous hydroxyapatite implants of varying density [J]. Journal of Materials Sciece:Materials Medicine,1999,10:663-670.
36 Ayers RA, Wolford LM, Bateman TA, Ferguson VL, Simske SJ. Quantification of bone ingrowth into porous block hydroxyapatite in humans [J]. Journal of Biomedical Materials and Research,1999,47:54-59.
37 Hing AK, Best SM, Tanner KE, BonfieldW, Revell PA.Mediation of bone ingrowth in porous hydroxyapatite bone graft substitutes [J]. Journal of Biomedical Materials and Research,2004,68A:187-200.
38 Gutierres M, Lopes MA, Hussain NS, Lemos AF, Ferreira JMF, Afonso A, Cabral AT, Almeida L, Santos JD. Bone ingrowth in macroporous Bonelike for orthopaedic applications [J]. Acta Biomaterialia,2008,4:370-377.
39 Lopes MA, Knowles JC, Santos JD, Monteiro FJ, Olsen I. Direct and Indirect effects of P2O5-glass reinforced-hydroxyapatite composites and growth and function of osteoblast-like cells [J]. Biomaterials,2000,21:1165-1172.
40 Lobato JV, Hussain NS, Botelho CM, et al. Titanium dental implants coated with Bonelike: clinical case report [J]. Thin Solid Films,2006,515:279.
41 Lopes MA, Santos JD,Monteiro FJ, Ohtsuki C, Osaka A, Kaneko S. Push-out testing and histological evaluation of glass reinforced hydroxyapatite composites implanted in the tibiae of rabbits [J]. Journal of Biomedicla Materials and Research,2001,54:463-469.
42 Koshino T, Murase T, Saito T. Medial opening-wedge high tibial osteotomy with use of porous hydroxyapatite to treat medial compartment osteoarthritis of the knee [J]. Journal of Bone and Joint Surgery-American,2003,85:78-85.
43 Gauthiera O, Boulerb JM, Aguadoa E, Piletb P, Daculsi G. Macroporous biphasic calcium phosphate ceramics:influence of macropore diameter and macroporosity percentage on bone ingrowth [J]. Biomaterials,1998,19:133-139.
44 Lia LH, Kommareddy KP, Pilz C, Zhou CR, Fratzl P, Manjubala I. In vitro bioactivity of bioresorbable porous polymeric scaffolds incorporating hydroxyapatite microspheres [J]. Acta biomateriala,2010,6:2525-2531.
1 Braddock M, Houston P, Campbell C, Ashcroft P. Born again bone:tissue engineering for bone repair [J]. News in Physiological Sciences,2001,16:208-213.
2 Goldberg VM, Stevenson S. Natural history of autografts and allografts [J]. Clinical Orthopaedics and Related Research,1987,225:7-16.
3 Costantino PD, Friedman CD. Synthetic bone graft substitutes [J]. Otolaryngologic Clinics of North America,1994,27:1037-1074.
4 Ma PX. Biomimetic materials for tissue engineering [J]. Advanced Drug Delivery Review, 2008,60:184-198.
5 Shin H, Jo S, Mikos AG. Biomimetic materials for tissue engineering [J]. Biomaterials, 2003,24:4353-4364.
6 Hay ED. Extracellular-matrix [J]. Journal of Cellular Biochemistry,1981,91:205-223.
7 Lutolf MP, Hubbell JA. Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering [J]. Natature Biotechnology, 2005,23:47-55.
8 LeGeros RZ. Properties of osteoconductive biomaterials:calcium phosphates [J]. Clinical Orthopaedics and Related Research,2002,395:81-98.
9余耀庭,张兴栋.生物医用材料[M].天津：天津大学出版社,2000：1-2.
10崔福斋,冯庆玲.生物材料学[M].北京：清华大学出版社,2004：1-2.
11 Akao M, Aoki H, Kato K. Mechanical properties of sintered hydroxyapatite for prosthetic applications [J]. Journal of Materials Science,1981,16:809-812.
12 Yoshikawa T, Ohgushi H, Nakajima H, Yamada E, Ichijima K, Tamai S. In vivo osteogenic durability of cultured bone in porous ceramics:a novel method for autogenous bone graft substitution [J]. Transplantation,2000,69:128-134.
13 De With G, Van Dijk HJA, Hattu N, Prijs K. Preparation, microstructure and mechanical properties of dense polycrystalline hydroxyapatite [J]. Journal of Materials Science,1981, 16:1592-1598.
14 Ma PX, Zhang RY. Microtubular architecture of biodegradable polymer scaffolds [J]. Journal of Biomedical Materials Research,2001,56:469-477.
15 Chen VJ, Ma PX. The effect of surface area on the degradation rate of nano-fibrous poly(L-lactic acid) foams [J]. Biomaterials,2006,27:3708-3715.
16 Ma PX, Zhang R. Synthetic nano-scale fibrous extracellular matrix [J]. journal of bone and mineral research,1999,46:60-72.
17 Woo KM, Wei GB, Ma PX. Enhancement of fibronectin-and vitronectin-adsorption to polymer/hydroxyapatite scaffolds suppresses the apoptosis of osteoblasts [J]. Journal of Bone and Mineral Research 2002,17:M49.
18 Wei GB, Ma PX. Structure and properties of nano-hydroxyapatite/polymer composite scaffolds for bone tissue engineering [J]. Biomaterials,2004,25:4749-4757.
19 Zhang RY, Ma PX. Biomimetic Polymer/Apatite Composite Scaffolds for Mineralized Tissue Engineering [J]. Macromelecular bioscience,2004,4:100-111.
20 Ma PX, Zhang R, Xiao GZ, Franceschi R. Engineering new bone tissue in vitro on highly porous poly(alpha-hydroxyl acids)/hydroxyapatite composite scaffolds [J]. Journal of Biomedical Materials Research,2001,54:284-293.
21 Langer R, Vacanti JP. Tissue engineering [J]. Science,1993,260:920-926.
22 Mikos AG, Thorsen AJ, Czerwonka LA, Bao Y, Langer R, Winslow DN, Vacanti JP. Preparation and characterization of poly(1-lactic acid) foams [J]. Polymer,1994,35: 1068-1077.
23 Whang K, Thomas CH, Healy KE, Nuber G. A novel method to fabricate bioabsorbable scaffolds [J]. Polymer,1995,36:837-842.
24 Mooney DJ, Baldwin DF, Suh NP, Vacanti JP, Langer R. Novel approach to fabricate porous sponges of poly(d,1-lactic-co-glycolic acid) without the use of organic solvents [J]. Biomaterials,1996,17:1417-1422.
25 Borden M, Attawia M, Laurencin CT. The sintered microsphere matrix for bone tissue engineering:in vitro osteoconductivity studies [J]. Journal of Biomedical Materials Research,2002,61:421-429.
26 Wintermantel E, Mayer J, Blum J, Eckert KL, Luscher P, Mathey M. Tissue engineering scaffolds using superstructures [J]. Biomaterials,1996,17:83-91.
27 Chen VJ, Laura AS, Ma PX. Bone regeneration on computer-designed nano-fibrous scaffolds [J]. Biomaterials,2006,27:3973-3979.
28 Wei GB, Ma PX. Macroporous and nanofibrous polymer scaffolds and polymer/bone-like apatite composite scaffolds generated by sugar spheres [J]. J Biomed Mater Res,2006, 78A:306-315.
29 Hu J, Feng K, Liu XH, Ma PX. Chondrogenic and osteogenic differentiations of human bone marrow-derived mesenchymal stem cells on a nanofibrous scaffold with designed pore network [J]. Biomaterials,2009,30:5061-5067.
30 Laura AS, Liu XH, Hu J, Ma PX. The influence of three-dimensional nanofibrous scaffolds on the osteogenic differentiation of embryonic stem cells [J]. Biomaterials,2009, 30:2516-2522.
31 Woo KM, Jun JH, Chen VJ, Seo J, Baek JH, Ryoo HM, Kim GS, Somerman JM, Ma PX. Nano-fibrous scaffolding promotes osteoblast differentiation and biomineralization [J]. Biomaterials,2007,28:335-343.
32 Woo KM, Seo J, Zhang RY, Ma PX. Suppression of apoptosis by enhanced protein adsorption on polymer/hydroxyapatite composite scaffolds [J]. Biomaterials,2007,28: 2622-2630.
33 Jiao YP, Liu ZH, Cui FZ, Zhou CR. Effect of Hydrolysis Pretreatment on the Formation of Bone-like Apatite on Poly(L-lactide) by Mineralization in Simulated Body Fluids [J]. Journal of Bioactive and Compatible Polymers,2007,22:492-507.
34 Yoshiro Y, Ayako O, Atsuo I. Biomimetic coating of an apatite layer on poly(1-lactic acid); improvement of adhesive strength of the coating [J]. Journal of Materials Science: Materials in Medicine,2007,18:1727-1734.
35 Niu XF, Feng QL, Wang MB, Guo XD, Zheng QX. Porous nano-HA/collagen/PLLA scaffold containing chitosan microspheres for controlled delivery of synthetic peptide derived from BMP-2 [J]. Journal of Controlled Release,2009,134:111-117.
36 Saito N, Murakami N, Takahashi J, Horiuchi H, Ota H, Kato H, Okada T, Nozaki K, Takaoka K, Synthetic biodegradable polymers as drug delivery systems for bone morphogenetic proteins[J]. Advanced Drug Delivery Reviews,2005,57:1037-1048.
37 Hu DS, Liu HJ, Pan IL. Inhibition of bovine serum albumin adsorption by poly (ethylene glycol) soft segment in biodegradable poly(ethylene glycol)/poly(L-lactide) copolymers [J]. Journal of Applied Polymer Science,1993,50:1391-1396.
38 Webster TJ, Ergun C, Doremus RH, Siegel RW, Bizios R. Specific proteins mediate enhanced osteoblast adhesion on nanophase ceramics [J]. Journal of Biomedical Materials Research,2000,51:475-483.
39 Webster TJ, Siegel RW, Bizios R. Osteoblast adhesion on nanophase ceramics [J]. Biomaterials,1999,20:1221-1227.
40 Yamada KM. Cell surface interactions with extracellular materials [J]. Annual Review of Biochemistry,1983,52:761-799.
41 Boal D. Machanics of the cell [M]. Cambridge University Press,2002.
1. S. V. Dorozhkin, M, Epple, Angew. Chem. Int. Ed.,2003,41,3130.
2. K.A. Khor, Y.W. Gu, C.H. Quek, P. Cheang, Surf. Coat. Tech.,2003,168,195.
3. G. Bezzi, G. Celotti, E. Landi. T.M.G. La Torretta, I. Sopyan, A. Tampieri, Mater. Chem. Phys.,2003,78, 816.
4. L.L. Hench, J. Wilson, Science,1984,226,630.
5. J. M. Gomez-Vega, E, Saiz, A.P. Tomisa, G.W. Marshall, S. J. Marshall, Biomaterials,2000,21,105.
6. Luo P, Nieh TG, Biomaterials,1996,17,1959.
7. Luo P, Nieh TG, Mater. Sci. Eng. C,1995,3,75.
8. Bertranda G, Roya P, Filiatreb C, Coddeta C, Chem. Eng. Sci.,2005,60,95.
9. Dyshlovcnko S, Pawlowski L, Roussel P, Muranob D, Maguer AL, Surf. Coat. Tech.,2006,200,3845.
10. Sun RX, Lu YP, Li MS, Li ST, Zhu RF, Surf. Coat. Tech.,2005,190,281.
11. Emily K. Cushnie, Yusuf M. Khan, Cato T. Laurencin, J. Biomed. Mater. Res.,2008,84A,54.
12. Vladimir S. K, Serguei MB, Elena VK, Biomaterials,2002,23,3449.
13.Allal B, Etienne L, Jacques L, Paul GR, J. Colloid. Interf. Sci.,1998,208,147.
14. Paul W, Nesamony J, Sharma CP, Technical Note,2001,12,660.
15. Shuji S, Kiminori A, Keijiro F, United States Patent 5,009,898.
16. Starling LB, Stephan JE, United States Patent 6,358,532.
17. A. S. Posner, F. Betts, Ace. Chem. Res.,1975,8,273.
18. E. D. Eanes, Gillesse I. H., A. S. Posner, Nature,1965,208,365.
19. M. Nagano, T. Nakamura, T. Kokubo, M. Tanahashi, M. Ogawa, Biomaterials,1996,17,1771.
20. S.H. Maxian, J.P. Zawadsky, M.G. Dunn, J. Biomed. Mater. Res.,1993,27,717.
21. R.J. Dekker, C.A. Van Blitterswijk, J.D. De Bruijn, M. Stigter, F. Barrere, P. Layrolle, Biomaterials, 2005,26,5231.
22. D. Skrtic, J.M. Antonucci, E.D. Eanes, R.T. Brunworth, J. Biomed. Mater. Res.,2002,59,597.
23. D. Hakimimehr, D.M. Liu, T. Troczynski, Biomaterials,2005,26,7297.
24. R.Z. Legeros, S. Lin, R. Rohanizadeh, D. Mijares, J.P. Legeros, J. Mater. Sci.:Mater. Med.,2003,14, 201.
25. S. Sadasivan, D. Khushalani, S. Mann, Chem. Mater.,2005,17,2765.
26. P. Layrolle, A. Lebugle, Chem. Mater.,1996,8,134.
27. P. Layrolle, A. Ito, T. Tateishi, J. Am. Ceram. Soc.,1998,81,1421.
28. Sebti S, Solhy A, Tahir R, Smahi A, Appl Catal A:Gen,2002,235,273.
29. Chen Shaoqiang, Zhu Ziqiang, Zhu Jianzhong, Appl. Surf. Sci.,2004,230,418.
30. L.M. RodrmH guez-Lorenzo, M. Vallet-RegmH, J.M.F. Ferreira, Biomaterials,2001,22,583.
31. Yanbao Li, Tjandra Wiliana, Kam C. Tam, Mater. Res. Bull.,2007,42,820.
32. Sujin Kim, Hyun-Seung Ryu, Hyunho Shin, Mater. Chem. Phys.,2005,91,500.
33. D. Tadic, F. Peters, M. Epple, Biomaterials,2002,23,2553.
34. Senya Inoue, Akira Ono, Nobuyuki Otaki, US patent 5,205,928.
35. Ruixue Sun, Yupeng Lu, Kezheng Chen, Mater. Sci. Eng. C,2009,29,1088.
2 Williams DF. On the nature of biomaterials [J]. Biomaterials,2009,30:5897-5909.
3 崔福斋,冯庆玲.生物材料学[M].北京：清华大学出版社,2004,1-2.
4 谈国强,苗鸿雁,宁青菊,夏傲.生物陶瓷材料[M].北京：化学工业出版社,2006,1-2.
5 Bres EF, Moebus G, Kleebe JJ, Pourry G, Wekmann J, Ehret G.. High resolution electron microscopy study of amorphous calcium phosphate [J]. Journal of Crystal Growth,1993, 129:149-162.
6 Hench LL. Biomaterials:a forecast for the future [J]. Biomaterials,1998,19:1419-1423.
7 Horlington M. Biomaterials:present and future [J]. Materials World,1995,3:332-333.
8 Vallet-Regi M, Gonzalez-Calbet JM. Calcium phosphates as substitution of bone tissues [J]. Progress in Solid States Chemistry,2004,32:1-31.
9 Wopenka B, Pasteris JD. A mineralogical perspective on the apatite in bone [J]. Materials Science and Engineering C,2005,25:131-143.
10 Zakharov NA, Polunina IA, Polunin KE, Rakitina NM, Kochetkova El, Sokolova NP, Kalinnikov VT. Calcium hydroxyapatite for medical applications [J]. Inorganic Materials, 2004,40:641-648.
11 Ginebra MP, Traykova T, Planell JA. Calcium phosphate cements:Competitive drug carriers for the musculoskeletal system [J]. Biomaterials,2006,27:2171-2177.
12 Rauschmann MA, Wichelhaus TA, Stirnal V, Dingeldein E, Zichner L, Schnettler R, Alt V. Nanocrystalline hydroxyapatite and calcium sulphate as biodegradable composite carrier material for local delivery of antibiotics in bone infections [J]. Biomaterials,2005,26: 2677-2684.
13 Madhavi S, Ferraris C, White TJ. Synthesis and crystallization of macroporous hydroxyapatite [J]. Journal of Solid State Chemistry,2005,178:2838-2845.
14刘国诠.生物工程下游技术[M].北京：化学工业出版社,2003,265-276.
15 Castner DG, Ratner BD. Biomedical surface science:Foundations to frontiers [J]. Surface Science,2002,500:28-60.
16 Komlev VS, Barinov SM, Koplik EV. A method to fabricate porous spherical hydroxyapatite granules intended for time-controlled drug release [J]. Biomaterials,2002, 23:3449-3454.
17 Jungbauer A, Hahn R, Deinhofer K, Luo P. Performance and characterization of a nanophased porous hydroxyapatite for protein chromatography [J]. Biotechnology and Bioengineering,2004,87:364-375.
18 Suchanek W, Yoshimura M. Processing and properties of hydroxyapatite-based biomaterials for use as hard tissue replacement implants [J]. Journal of Materials Research,1998,13:94-117.
19 Ito A, Nakamura S, Aoki H, Teraoka K, Onuma K, Tateishi T. Hydrothermal growth of carbonate-containing hydroxyapatite single crystals [J]. Journal of Crystal Growth,1996, 163:311-317.
20李新化,郑治祥,汤文明,吕君,刘君武.羟基磷灰石生物陶瓷材料的现状及展望[J].合肥工业大学学报,2002,25：1148-1153.
21 Lopes MA, Knowles JC, Santos JD. Structural insights of glass-reinforced hydroxyapatite composites by rietveld refinement [J]. Biomaterials,2000,21:1905-1910.
22 Leventouri Th. Synthetic and biological hydroxyapatites:Crystal structure questions [J]. Biomaterials,2006,27:3339-3342.
23 Yasushi S, Junzo T. Crystal growth and structure analysis of twin-free monoclinic hydroxyapatite [J]. Journal of Materials Science:Materials in Medicine,2002,13: 767-772.
24 Kay MI, Young RA, Posner AS. Crystal structure of hydroxyapatite [J]. Nature,1964,204: 1050-1052.
25 Weiner S, Wagner HD. Material bone:structure-mechanical function relations [J]. Annual Review of Materials Science,1998,28:271-98.
26 Dorozhkin SV. Calcium orthophosphates in nature, biology and medicine [J]. Materials, 2009,2:399-498.
27 Davies JE. In vitro modeling of the bone/implant interface [J]. Anatomical Record-Advances in Integrative Anatomy and Evolutionary Biology,1996,245:426-445.
28 Anselme K. Osteoblast adhesion on biomaterials [J]. Biomaterials,2000,21:667-681.
29 Sergey V. Dorozhkin. Bioceramics of calcium orthophosphates [J]. Biomaterials,2010,31: 1465-1485.
30李世普.生物医用材料导论[M].武汉：武汉工业大学出版社,2000,84-95.
31 Yuan HP, Kurashina K, de Bruijn JD, Li YB, de Groot K, Zhang XD. A preliminary study on osteoinduction of two kinds of calcium phosphate ceramics [J]. Biomaterials,1999,20: 1799-1806.
32 Zheng XB, Huang MH, Ding CX. Bond strength of plasma-sprayed hydroxyapatite/Ti composite coatings [J]. Biomaterials,2000,21:841-849.
33储成林,朱景川,尹钟大,王世栋.羟基磷灰石(HA)生物复合材料的研究进展[J].材料导报,1999,13：51-54.
34 Chiba A, Sahakura S, Kobayashi K, Kusayanagi K. Dissolution amounts of nickel, chromium and iron from SUS 304,316 and 444 stainless steels in sodium chloride solution[J]. Journal of Materials Science,1997,32:1995-2000.
35顾其胜,侯春林,徐政.实用生物医用材料学[M].上海：上海科学技术出版社,2005,9：106-107.
36 Chen YM, Lu YP, Li MS. Surface changes of plasma-sprayed hydroxyapatite coatings before and after heat treatment [J]. Surface Engineering,2006,22:462-467.
37 Ding SJ, Su YM, Ju CP, Lin JHC. Structure and immersion behaviour of plasma sprayed apatite-matrix coatings [J]. Biomaterials,2001,22:833-845.
38 Xiao GY, Lu YP, Zhu RF, Xu WH, et al. Effect of heat-treatment on the performance of hydroxyapatite coatings immersed in SBF [J]. Surface Engineering,2009,25:136-140.
39 Xiao GY, Lu YP, Zhu RF, Li ST, Wang AJ. Effect of post-heat treatment on inner planar microstructure and mechanical performance of hydroxyapatite coating [J]. Surface Engineering,2008,24:307-312.
40 Gotfredsen Klaus, Wennerberg Ann, Johansson Carina, Skovgaard Lene Teil, Hjorting-Hansen Erik. Anchorage of TiO2-blasted, HA-coated, and machined implants:an experimental study with rabbits [J]. Journal of Biomedical Materials Research,1995,29 10:1223-1231.
41 Weng J, Liu XG, Zhang XD, Ma Z, Ji X, Zyman Z. Further studies on the plasma-sprayed amorphous phase in hydroxyapatite coatings and its deamorphization [J]. Biomaterials, 1993,14:578-582.
42 Jin HH, Lee CH, Lee WK, Lee JK, Park HC, Yoon SY. In-situ formation of the hydroxyapatite/chitosan-alginate composite scaffolds [J]. Mareials Letters,2008,62, 1630-1633.
43 Sanchez-Salcedo S, Nieto A, Vallet-Regi M. Hydroxyapatite/β-tricalcium phosphate/agarose macroporous scaffolds for bone tissue engineering [J]. Chemical Engineering Journal,2008,137,62-71.
44 Liu XH, Laura A, Smith, Hu J, Ma PX. Biomimetic nanofibrous gelatin/apatite composite scaffolds for bone tissue engineering [J]. Biomaterials,2009,30:2252-2258.
45 Uhrich KE, Cannizzaro SM, Langer RS, Shakesheff KM. Polymeric systems for controlled drug release [J]. Chemical Reviews,1999,99:3181-3198.
46 Zhang JX, Ma PX. Polymeric Core-Shell Assemblies Mediated by Host-Guest Interactions: Versatile Nanocarriers for Drug Delivery [J]. Angewandte Chemie International Edition, 2009,48:964-968.
47 Zhang JX, Sun HL, Ma PX. Host-Guest Interaction Mediated Polymeric Assemblies: Multifunctional Nanoparticles for Drug and Gene Delivery [J]. Acs Nano,2010,4: 1049-1059.
48 Almirall A, Larrecq G, Delgado JAA. Fabrication of low temperature macroporous hydroxyapatite scaffolds by foaming and hydrolysis of an alpha-TCP paste [J]. Biomaterials,2004,17:3671-3680.
49 Barralet JE, Lilley KJ, Grover LM, Farrar DF, Ansell C, Gburecka U. Cements from nanocrystalline hydroxyapatite [J]. Journal of Materials Science:Materials in Medicine, 2004,15:407-411.
50 Queiroz AC, Santos JD, Monteiro FJ. Porous HA scaffolds for drug releasing [J]. Bioceramics,2005,17:407-410.
51 Rauschmann MA, Wichelhaus TA, Stirnal V, Dingeldein E, Zichner L, Schnettler R, et al. Nanocrystalline hydroxyapatite and calcium sulphate as biodegradable composite carrier material for local delivery of antibiotics in bone infections [J]. Biomaterials,2005,26: 2677-2684.
52 Yang HH, Zhu QZ, Qu HY, Chen XL, Din MT, Xu JG. Flow injection fluorescence immunoassay for gentamicin using sol-gel derived mesoporous biomaterial [J]. Analytical Biochemistry,2002,308:71-76.
53 Caliceri P, Salmaso S, Lante A, Yoshida M, Katakai R, Martellini F, et al. Controlled release of biomolecules from temperature-sensitive hydrogels prepared by radiation polymerization [J]. Journal of Controlled Release,2001,75:173-181.
54 Changez M, Burugapalli K, Koul V, Choudhary V. The effect of composition of poly (acrylic acid)-gelatin hydrogel on gentamicin sulphate release:in vitro [J]. Biomaterials, 2003,24:527-536.
55 Zhu YF, Shi JL, Shen WH, Dong XP, Feng JW, Ruan ML, et al. Stimuli-responsive controlled drug release froma hollow mesoporous silica sphere/polyelectrolyte multilayer core-shell structure [J]. Angewandte Chemie International Edition,2005,44:5083-5087.
56 Fu Q, Rama Rao GV, Ista LK, Wu Y, Andrzejewski BP, Sklar LA, et al. Control of molecular transport through stimuli-responsive ordered mesoporous materials [J]. Advanced Materials,2003,15:1262-1266.
57 Andersson J, Rosenholm J, Areva S, Linde'n M. Influences of material characteristics on ibuprofen drug loading and release profiles from ordered microand mesoporous silica matrices [J]. Chemistry of Materials,2004,16:4160-4167.
58 Zhou J, Wu W, Caruntu D, Yu MH, Martin A, Chen JF, et al. Synthesis of porous magnetic hollow silica nanospheres for nanomedicine application [J]. Journal of Physical Chemistry C,2007,111:17473-17477.
59 Barroug A, Kuhn LT, Gerstenfeld LC, Glimcher MJ. Interactions of cisplatin with calcium phosphate nanoparticles:in vitro controlled adsorption and release [J]. Journal of orthopaedic research,2004,22:703-708.
60 Stigter M, De Groot K, Layrolle P. Incorporation of tobramycin into biomimetic hydroxyapatite coating on titanium [J]. Biomaterials,2002,23:4143-4153.
61 Del Real RP, Padilla S, Vallet-Regi M. Gentamicin release from hydroxyapatite/poly (ethyl methacrylate)/poly (methyl methacrylate) composites [J]. Journal of Biomedical Materials Research Part A,2000,52:1-7.
62 Sivakumar M, Panduranga Rao K. Preparation, characterization and in vitro release of gentamicin from coralline hydroxyapatite-alginate composite microspheres [J]. Journal of Biomedical Materials Research Part A,2003,65:222-228.
63 Sivakumar M, Manjubala I, Panduranga Rao K. Preparation, characterization and in vitro release of gentamicin from coralline hydroxyapatite-chitosan composite microspheres [J]. Carbohydrate Polymers,2002,49:281-288.
64 Barroug A, Glimcher MJ. Hydroxyapatite crystals as a local delivery system for cisplatin: absorption and release of cisplatin in vitro [J]. Journal of orthopaedic research,2002,20: 274-280.
65 Paul W, Sharma CP. Development of porous spherical hydroxyapatite granules:application towards protein delivery [J]. Journal of Materials Science:Materials in Medicine,1999, 10:383-388.
66孙瑞雪.多孔及空心羟基磷灰石微球的制备与表征[D].山东大学博士毕业论文,2007，06.
67 Yang Piaoping, Wuan Zewei, Li Chunxia, Kang Xiaojiao, Lian Hongzhou, Lin Jun. Bioactive, Luminescent and mesoporous europium-doped hydroxyapatite as a drug carrier [J]. Biomaterials,2008,29:4341-4347.
68李校望.药物蛋白质分离纯化技术[M].北京：化学工业出版社,2004,1：157-158.
69余晓英,周纯益,余贤真,欧阳藩.新型、高效球形羟基磷灰石分离介质[J].生物工程进展,1996,16：17.
70 Shepard SR, Stone CB, Schrimsher JL, Koch G. Discoloration of ceramic hydroxyapatite used for protein chromatography [J]. Journal of Chromatography A,2000,891:93.
71王爱娟.羟基磷灰石微球分离介质的制备与结构和性能分析[D].山东大学博士毕业论文,2009,06.
72 Paul W, Sharma CP. Modified hydroxyapatite microsphere as immunoadsorbent for plasma perfusion:preliminary study [J]. Journal of Colloid and Interface Science,1995,174: 224-229.
73 Barroug A., Fastrez J., Lemattre J., Rouxhet P.. Adsorption of succinylated lysozyme on hydroxyapatite [J]. Journal of Colloid and Interface Science,1997,189:37-42.
74 Eis C, Griessler R, Maier M, Weinhausel A. Efficient downstream processing of maltodextrin phosphorylase from escherichia and stabilization of the enzyme by immobilization onto hydroxyapatite [J]. Journal of Biotechnology,1997,58:157-166.
75陈向东,吴梧桐,高向东,吕树军,张奉国,吕正兵.卡介菌多糖的分离纯化与药效研究[J].中国天然药物,2003,1：173-177.
76 Ford CHJ, Osborne PO, Mathew A, Rego BG. Affinity purification of novel bispecific antibodies recognizing carcinoembryonic antigen and doxorubicin [J]. Journal of Chromatography B,2001,754:427-435.
77 Herve F, Fouache F, Marche C, Tillement J P. Abnormal microheterogeneity detected in one commercial a 1-acid glycoprotein preparation using chromatography on immobilized metal affinity adsorbent and on hydroxyapatite [J]. Journal of Chromatography B,1997, 688:35-46.
78 Steen S, Steen JJ, Anders HJ. Purification and characterization of osteopontin from human milk [J]. Protein Expression and Purification,2003,30:238-245.
79 Lai H, Franklin SG. Purification of Murine IgGl using UNO sphere S and CHT Ceramic hydroxyapatite chromatography [J]. Bio-Rad Laboratories, tech note 2780. http://www. bio-rad.com.
80 Ordunez C, Franklin S G. Purification of horse IgGT using macro-prep DEAE and CHT Ceramic hydroxy-apatite type I supports [J]. Bio-Rad Laboratories, tech note 2524. http://www. bio-rad.com.
81 Meijer AG, Segenhout HM, Albers FW, et al. Histopathology of biocompatible hydroxyapatite-polyehylene composite in ossiculoplasty [J]. ORL J Otorhinolaryngol Related Specialties,2002,64:173-179.
82 Moursi AM, Winnard AV, Winnard PL, et al. Enhanced osteoblast response to a polymethylmethacrylate-hydroxyapatite composite [J]. Biomaterials,2002,23:133-144.
83 Salih V, Georgiou G, Knowles JC, et al. Glass reinforced hydroxyapatite for hard tissue surgery-part Ⅱ:in vitro evalution of bone cell growth and function [J]. Biomaterials, 2001,22:2817-2825.
84 Zhang Y, Ni M, Zhang M, et al. calcium phosphate-chitosan composite scaffolds for bone tissue engineering [J]. Tissue engineering,2003,9:337-342.
85 Zhang Y, Zhang M. Calcium phosphate/chitosan composite scaffolds for controlled in vitro antibiotic drug release [J]. Journal of Biomedical Materials Research,2002,62: 378-386.
86 Zhao F, Yin Y, Lu WW, et al. Preparation and histological evaluation of biomimetic three-dimensional hydroxyapatite/chitosan-gelatin network composite scaffolds [J]. Bioamtierials,2002,23:3227-3234.
87 Zhang RY, Ma PX. Biomimetic polymer/apatite composite scaffolds for mineralized tissue engineering [J]. Macromolecular Bioscience,2004,4:100-111.
88 Wei GB, Ma PX. Structure and properties of nano-hydroxyapatite/polymer composite scaffolds for bone tissue engineering [J]. Biomaterials,2004,25:4749-4757.
89 Niu XF, Feng QL, Wang MB, Guo XD, Zheng QX. Porous nano-HA/collagen/PLLA scaffold containing chitosan microspheres for controlled delivery of synthetic peptide derived from BMP-2 [J]. Journal of Controlled Release,2009,134:111-117.
90候小宝,谢田甜,刘志信,夏志军.羟基磷灰石的制备方法[P].中国发明专利,200410067736.7(2004).
91 Genin F. Luo YP, Dash AK. Hydroxyapatite based drug delivery implant for cancer treatment [P]. US Patent,6767550 (2004).
92 Troczynski T, Liu DM, Yang QZ. Biofunctional hydroxyapatite coatings and microspheres for in-situ drug encapsulation [P]. US Patent,6730324 (2004).
93 Fukue N, Tatsuya M, Yoshiyuki Y. A method to fabricate hydroxyapatite/poly(lactic acid) microspheres intended for biomedical application [J]. Journal of the European Ceramic Society,2006,26:533-553.
94 Sun RX, Lu YP, Li MS, Li ST, Zhu RF. Characterization of hydroxyapatite particles plasma-sprayed into water [J]. Surface and Coatings Technology,2005,190:281-286.
95 Sun RX, Chen KZ, Lu YP. Fabrication and dissolution behavior of hollow hydroxyapatite microspheres intended for controlled drug release [J]. Materials Research Bulletin,2009, 44:1939-1942.
96 Huang WH, Rahaman MN, Delbert ED, Brad AM. Strength of hollow hydroxyapatite microspheres prepared by a glass conversion process [J]. Journal of Materials Science: Materials in Medicine,2009,20:123-129.
97 Paul W, Nesamony J, Sharma CP. Delivery of insulin from hydroxyapatite ceramic microspheres:Preliminary in vivo studies [J]. Journal of Biomedical Materials Research Part A,2002,61:660-662.
98 Kweh SWK, Khor KA, Cheang P. The production and characterization of hydroxyapatite (HA) powders [J]. Journal of Materials Processing Technology,1999,89-90:373-377.
99 Keishiro T, Hidehiko A, Takatomo N, Kimiko M. Hydroxyapatite particles as drug carriers for proteins [J]. Colloids and Surfaces B:Biointerfaces,2010,76:226-235.
100 Lee HH, Hong SJ, Kim CH et al. Preparation of hydroxyapatite spheres with an internal cavity as a scaffold for hard tissue regeneration [J]. Journal of Materials Science: Materials in Medicine,2008,19:3029-3034.
101 Gao F, Su ZG, Wang P, Ma GH. Double emulsion templated microcapsules with single hollow cavities and thickness-controllable shells [J]. Langmuir,2009,25: 3832-3838.
102 Hong SJ, Yu HS, Kim HW. Tissue engineering polymeric microcarriers with macroporous morphology and bone-bioactive surface [J]. Macromolecular bioscience,2009,9: 639-645.
103 Lou XW, Archer A., Yang ZC. Hollow micr-/nanostructures:synthesis and applications [J]. Advanced materials,2008,20:3987-4019.
104 Caruso F, Caruso RA, Mohwald H. Nanoengineering of inorganic and hybrid hollow spheres by colloidal templating [J]. Science,1998,282:1111-1114.
105 Caruso, F. Nanoengineering of particle surfaces [J]. Advanced materials,2001,13:11-22.
106 Caruso F, Spasova M. Multilayer assemblies of silica-encapsulated gold nanoparticles on decomposable colloid templates[J]. Advanced materials,2001,13:1090-1094.
107 Valtchev V, Mintova S. Layer-by-layer preparation of zeolite coatings of nanosized crystals[J]. Microporous and Mesopouous Materials,2001,43:41-49.
108 Dyshlovenko S, Pawlowski L, Roussel P, Muranob D, Le Maguer A. Relationship between plasma spray operational parameters and microstructure of hydroxyapatite coatings and powder particles sprayed into water[J]. Surface and Coatings Technology, 2006,200:3845-3855.
109 Dyshlovenko S, Pateyron B, Pawlowski L, Murano D. Numerical simulation of hydroxyapatite powder behaviour in plasma jet [J]. Surface and Coatings Technology, 2004,179:110-117.
110 Bertling J, Blomer J, Kummel R. Hollow microspheres [J]. Chemical Engineering & Technology,2004,27:829-837.
111 Bertranda G, Roy P, Filiatre C, Coddet C. Spray-dried ceramic powders:Aquantitative correlation between slurry characteristics and shapes of the granules [J]. Chemical Engineering Science,2005,60:95-102.
112 Luo P, Nieh TG. Preparing hydroxyapatite powders with controlled morphology [J]. Biomaterials,1996,17:1959-1964.
113 Li GC, Zhang ZK. Synthesis of submicrometer-sized hollow titania spheres with controllable shells [J]. Materials Letters,2004,58:2768-2771.
114 Goula AM, Adamopoulos KG. Spray drying of tomato pulp in dehumidified air:Ⅱ The effect on powder properties [J]. Journal of Food Engineering,2005,66:35-42.
115 Goula AM, Adamopoulos KG. Spray drying of tomato pulp in dehumidified air:Ⅰ. The effect on product recovery [J]. Journal of Food Engineering,2005,66:25-34.
116 Apinan S, Fanny B, Hidefumi Y, Takeshi F, Masaaki O, Pekka L. Influence of emulsion and powder size on the stability of encapsulated d-limonene by spray drying [J]. Innovative Food Science and Emerging Technologies,2005,6:107-114.
117 Ma PX. Scaffold for tissue engineering [J]. Materials today,2004,5:30-40.
118 Kim HW, Song JH, Kim HE. Nanofiber generation of gelatin-hydroxyapatite biomimetics for guided tissue regeneration [J]. Advanced Functional Materials,2005,15:1988-1994.
119 Fujihara K, Kotaki M, Ramakrishna S. Guided bone regeneration membrane made of polycaprolactone/calcium carbonate composite nano-fibers [J]. Biomaterials,2005,26: 4139-4147.
120 Li C, Vepari C, Jin HJ, Kim H, Kaplan D. Electrospun silk-BMP-2 scaffolds for bone tissue engineering [J]. Biomaterials,2006,27:3115-3124.
121 Sui G, Yang X, Mei F, Hu X, Chen G, Deng X, et al. Poly-L-lactic acid/hydroxyapatite hybrid membrane for bone tissue regeneration [J]. Journal of Biomedical Materials Research, Part A 2007,82A:445-454.
122 Deng XL, Sui G, Zhao ML, Chen GQ, Yang XP. Poly(L-lactic acid)/hydroxyapatite hybrid nanofibrous scaffolds prepared by electrospinning [J]. Journal of Biomaterials Science:Polymer Edition,2007,18:117-130.
123 Catledge SA, Clem WC, Shrikishen N, Chowdhury S, Stanishevsky AV, Koopman M, et al. An electrospun triphasic nanofibrous scaffold for bone tissue engineering [J]. Journal of Biomedical Materials Research,2007,2:142-150.
124 Venugopal J, Vadgama P, Kumar TSS, Ramakrishna S. Biocomposite nanofibres and osteoblasts for bone tissue engineering [J]. Nanotechnology,2007,18:1-8.
125 Liu XH, Smith LA, Wei GB, Won YG, Ma PX. Surface engineering of nano-fibrous poly(L-Lactic acid) scaffolds via self-assembly technique for bone tissue engineering [J]. Journal of biomedical nanotechnology,2005,1:54-60.
126 Smith LA, Liu XH, Hu J, Ma PX. The influence of three-dimensional nanofibrous scaffolds on the osteogenic differentiation of embryonic stem cells [J]. Biomaterials, 2009,30:2516-2522.
127 Liu XH, Ma PX. Phase separation, pore structure, and properties of nanofibrous gelatin scaffolds [J]. Biomaterials,2009,30:4094-4103.
128 Ma PX, Zhang RY. Microtubular architecture of biodegradable polymer scaffolds [J] Journal of Biomedical Materials Research,2001,56,469-483.
1 Li YB, Wiliana T, Tam KC. Synthesis of amorphous calcium phosphate using various types of cyclodextrins [J]. Materials Research Bulletin,2007,42:820-827.
2 Zhang J, Gao X, Song BC, Wang ZF, Lu WW. A novel technique to synthesize hydroxyapatite whiskers[J]. Materials Letters,2008,62:1162-1164.
3 http://china.kytl.com/technology.aspx?cid=6&id=51
4 Tadashi Kokubo, Hiroaki Takadama. How useful is SBF in predicting in vivo bone bioactivity [J]? Biomaterials,2006,27:2907-2915.
5 Zhang RY, Ma PX. Poly(alpha-hydroxy acides)/hydroxyapatite porous composites for bone tissue engineering:1. Preaparation and morphology [J]. Journal of Biomedical Materials Research,1999,44:446-455.
6 Ma PX, Zhang RY, Xiao GZ, Franceschi R. Engineering new bone tissue in vitro on highly porous poly(alpha-hydroxyl acids)/hydroxyapatite composite scaffolds [J]. Journal of Biomedical Materials Research,2001,54:284-293.
7 Liu XH, Won YJ, Ma PX. Porogen-induced surface modification of nano-fibrous poly(L-lactic acid) scaffolds for tissue engineering [J]. Biomaterials,2006,27:3980-3987.
8 Xiao G, Cui Y, Ducy P, Karsenty G, Franceschi RT. Ascorbic acid-dependent activation of the osteocalcin promoter in MC3T3-E1 preosteoblasts:Requirement for collagen matrix synthesis and the presence of an intact OSE2 sequence [J]. Molecular Endocrinology,1997, 11:1103-1113.
9 Franceschi RT, Iyer BS. Relationship between collagen synthesis and expression of the osteoblast phenotype in MC3T3-E1 cells [J]. Journal of Bone and Mineral Research,1992, 7:235-246.
10 Schneider WC. Determination of nucleic acids in tissues by pentose analysis. Methods Enzymol,1957,3:680-684.
1 Luo P, Nieh TG. Preparing hydroxyapatite powders with controlled morphology [J]. Biomaterials,1996,17:1959-1964.
2 Luo P, Nieh TG. Synthesis of ultrafine hydroxyapatite particles by a spray dry method [J]. Materials Science and Engineering C,1995,3:75-78.
3 Bertranda G, Roya P, Filiatreb C, Coddeta C. Spray-dried ceramic powders:A quantitative correlation between slurry characteristics and shapes of the granules [J]. Chemical Engineering Science,2005,60:95-102.
4 Wang AJ, Lu YP, Sun RX. Recent progress on the fabrication of hollow microspheres [J]. Materials Science and Engineering A.2007,460-461:1-6.
5 李英霞,邹彪,田景振,周苏宁.喷雾干燥技术[J].山东中医杂志,2000,6：371-372.
6 王宝和,王喜忠.喷雾干燥技术的现状及展望[J].化工装备技术,1997,18：46-50.
7 黄立新,王宗濂,唐金鑫.我国喷雾干燥技术研究及进展[J].化学工程,2001,29：51-55.
8 张文孝,姚学勇,王玉德.喷雾干燥现状及展望[J].食品与机械,2004,20：33-35.
9 Wang AJ, Lu YP, Zhu RF, Li ST, Xiao GY, Zhao GF, Xu WH. Effect of sintering on porosity, phase and surface morphology of spray dried hydroxyapatite microspheres[J]. Journal of Biomedical Materials Research,2008,87A:557-562.
10孙瑞雪.多孔及空心羟基磷灰石微球的制备与表征[D].山东大学博士毕业论文,2007，06.
11王爱娟.羟基磷灰石微球分离介质的制备与结构和性能分析[D].山东大学博十毕业论文,2009,06.
12 Posner A, Betts SF. Synthetic amorphous calcium phosphate and its relation to bone mineral structure [J]. Accounts of Chemical Research,1975,8:273-281.
13 Dekker RJ, Van Blitterswijk CA, De Bruijn JD, Stigter M, Barrere F, Layrolle P.. Bone tissue engineering on amorphous carbonated apatite and crystalline octacalcium phosphate-coated titanium discs [J]. Biomaterials,2005,26:5231-5239.
14 Hakimimehr D, Liu DM, Troczynski T. In-situ preparation of poly(propylene fumarate)—hydroxyapatite composite. Biomaterials,2005,26:7297-7303.
15 Sun RX, Chen K.Z, Lu YP. Fabrication and dissolution behavior of hollow hydroxyapatite microspheres intended for controlled drug release [J]. Materials Research Bulletin,2009, 44:1939-1942.
16 Wang AJ, Lu YP, Zhu RF, Li ST, Xu WH. Effect of process parameters on the performance of spray dried HAM [J]. Powder technology,2009,191:1-6.
17 Sun R, Lu Y, Chen K. Preparation and characterization of hollow hydroxyapatite microspheres by spray drying method [J]. Materials science and engineering C,2009,29: 1088-1092.
18 Ferry I, Gradon L, Okuyama K. Control of the morphology of nanostructured particles prepared by the spray drying of a nanoparticle sol [J]. Journal of Colloid and Interface Science,2003,265:296-303.
19 Sun R, Li M, Lu Y, Wang A. Immersion behavior of hydroxyapatite (HA) powders before and after sintering [J]. Materials Characterization,2006:250-254.
20 Kweh SWK, Khor K A, Cheang P. The production and characterization of hydroxyapatite (HA) powders [J]. Journal of Materials Processing Technology,1999,89-90:373-377.
21 Patel N, Glbson I R, Ke S, Best S M, Bonfield W. Calcining influence on the powder properties of hydroxyapatite [J]. Journal of Materials Science:Materials in Medicine, 2001,12:181-188.
22 Sunny MC., Ramesh P, Varma HK. Microstructured microspheres of hydroxyapatite bioceramic[J]. Journal of Materials Science:Materials in Medicine,2002,13:623-632
23 Patel N, Gibson I Ke RS, Best SM, Bonfield W. Calcining influence on the powder properties of hydroxyapatite [J]. Journal of Materials Science:Materials in Medicine, 2001,12:181-188.
24 Raynaud S, Champion E, Bernache-Assollant D. Calcium phosphate apatites with variable Ca/P atomic ratio II. Calcination and sintering [J]. Biomaterials,2002,23:1073-1080.
25 Deepak K. Pattanayak, Rajalaxmi Dash, R.C. Prasad, B.T. Rao, T.R. Rama Mohan. Synthesis and sintered properties evaluation of calcium phosphate ceramics[J]. Materials Science and Engineering C,2007,27:684-690.
26 Senya I, Akira O, Nobuyuki O. Process for the preparation of microspherical sintered bodies of hydroxyapatite and a chromatographic packing material comprising the microspherical sintered bodies of hydroxyapatite [P]. US patent,5,205,928.
27郑月华,候小妹,杨兆雄.多孔HA生物陶瓷进展[J].硅酸盐通报.1995,3：20-24.
28史坚.现代柱色谱分析[M].上海：上海科学技术文献出版社.1988,7：104-106.
29石海涛.胰岛素-多孔羟基磷灰石微球口服给药系统的研究[D].四川大学博十学位论文.2005,11.
30 Bailliez S, Nzihou A. The kinetics of surface area reduction during isothermal sintering of hydroxyapatite adsorbent [J]. Chemical Engineering Journal,2004,98:141-152.
31 Caillet DA, Harrisson DP. Structural property variations in the MnO-MnS system [J], Chemical Engineering Science,1982,37:625-636.
32 Beckman-Coulter公司,COULTER-SA3100型表面积与孔隙分析仪说明书[M].
33 Raynaud S, Champion E, Bernache-Assollant D. Calcium phosphate apatites with variable Ca/P atomic ratio Ⅱ. Calcination and sintering [J]. Biomaterials,2002,23:1073-1080.
34 Sun R, Li M, Lu Y, An X. Effect of titanium and titania on chemical characteristics of hydroxyapatite plasma-sprayed into water [J]. Materials Science and Engineering C,2006, 26:28-33.
35 Tsui YC, Doyle C, Clyne TW. Plasma sprayed hydroxylapatite coatings on titanium substrates Part 2:optimization of coating properties [J]. Biomaterials,1998,19: 2031-2043.
36 Ding SJ, Huang TH, Kao CT. Immersion behavior of plasma-sprayed modified hydroxyapatite coatings after heat treatment [J]. Surface and Coatings Technology,2003, 165:248-257.
37 Tadic D, Peters F, Epple M. Continuous synthesis of amorphous carbonated apatites [J]. Biomaterials,2002,23:2553-2559.
38 Senya I, Akira O, Nobuyuki O. Process for the preparation of microspherical sintered bodies of hydroxyapatite and a chromatographic packing material comprising the microspherical sintered bodies of hydroxyapatite [P]. US patent,5,205,928 (1993).
39李明欧,肖秀峰,刘榕芳.含锌羟基磷灰石的水热合成与结构表征[J].硅酸盐学报,2008,36：378-382.
40 Joris SJ, Amberg CH. The nature of deficiency in non-stoichiometric hydroxyapatites [J]. The Journal of Physical Chemistry,1971,75:3172-3178.
41 Baddiel CB, Berry E. Spectra structure correlation in hydroxyl and fluorapatites [J]. Spectrochimica Acta Part A,1996,22:1407-1416.
42 Gonzalez-diaz PF, Santos M. On the hydroxyl ions in apatite [J]. Journal of Solid State Chemistry,1997,2:193-199.
43温喜梅,张军,宋邦才,马兰.水热条件下羟基磷灰石晶须的制备[J].中国陶瓷,2008，44：31-33.
44 Senamaud N, Bemache-Assollant D, Champion E, Heughebaert M, Rey C. Calcination and sintering of hydroxyfluorapatite powders[J]. Solid State Ionics,1997,101-103: 1357-1362.
45 Guo XY, Xiao P. Effects of solvents on properties of nanocrystalline hydroxyapatite produced from hydrothermal process [J]. Journal of the European Ceramic Society,2006, 26:3383-3391.
46 Lin F H, Li CJ, Chen KS, Sun JS. Thermal reconstruction behavior of the quenched hydroxyapatite powder during reheating in air [J]. Materials Science and Engineering C, 2000,13:97-104.
47 Nishikawa H. Thermal behavior of hydroxyapatite in structural and spectrophotometric characteristics [J]. Materials Letters,2001,50:364-370.
1 Rueger JM, Linhart W, Sommerfeldt D. Biological reactions to calcium phosphate ceramic implants. Results of animal experiments [J]. Orthop.ade,1998,27:89-95.
2 Stupp SI, Hanson JA,Eurell JA,Ciegler GW,Johnson A. Organoapatites:materials for artificial bone. III. Biological testing [J]. Journal of Biomedical Materials Research,1993, 27:301-311.
3 Du C, Cui FZ., Feng QL., Zhu XD, de Groot K. Tissue response to nano-hydroxyapatite/collagen composite implants in marrow cavity [J]. Journal of Biomedical Materials Research,1998,42:540-548.
4 Silver IA, Murrils RJ, Etherington DJ. Microelectrode studies on the acid microenvironment beneath adherent macrophages and osteoclast [J]. Experimental Cell Research,1988,175:266-276.
5 Vaes G. Cellular biology and biochemical mechanism of bone resorption [J]. Clinical Orthopaedics and Related Research,1988,231:239-271.
6 Teitelbaum SL, Tondravi MM, Ross FP. Osteoclasts, macrophages, and the molecular mechanisms of bone resorption [J]. Journal of Leukocyte Biology,1997,61:381-388.
7 Weiner S, Wagner HD. The material bone:structure-mechanical function relations [J]. Annual Review of Materials Research,1998,28:271-298.
8 Tadic D, Peters F, Epple M. Continuous synthesis of amorphous carbonated apatites [J]. Biomaterials,2002,23:2553-2559.
9 Doi Y, Shibutani T, Moriwaki Y, Kajimoto T, Iwayama Y. Sintered carbonate apatites as bioresorbable bone substitutes [J]. Journal of Biomedical Materials Research,1998,39: 603-610.
10 Shellis RP, Lee AR, Wilson RM. Observations on the apparent solubility of carbonate-apatites [J]. Journal of Colloid and Interface Science,1999,218:351-358.
11 Marion D. Francis. The inhibition of calcium hydroxyapatite crystal growth by polyphosphonates and polyphosphates [J]. Calcified Tissue International,1969,3: 151-162.
12 Suchanek W, Yoshimura M. Processing and properties of hydroxyapatite-based biomaterials for use as hard tissue replacement implants [J]. Journal of Materials Research,1998,13:94-117.
13余耀庭,张兴栋.生物医用材料[M].天津：天津大学出版社,2000：1-2.
14崔福斋,冯庆玲.生物材料学[M].北京：清华大学出版社,2004：1-2
15谈国强,苗鸿雁,宁青菊,夏傲.生物陶瓷材料[M].北京：化学工出版社,2006：1-2.
16 Viswanath B, Ravishankar N. Controlled synthesis of plate-shaped hydroxyapatite and implications for the morphology of the apatite phase in bone [J]. Biomaterials,2008,29: 4855-4863.
17 Li S, Xu J, Luo G. Control of crystal morphology through supersaturation ratio and mixing conditions [J]. Journal of Crystal Growth,2007,304:219-224.
18 Yang G, Kubota N, Sha Z, Louhi-Kultanen M, Wang J. Crystal shape control by manipulating supersaturation in batch cooling crystallization [J]. Crystal Growth & Design,2006,6:2799-2803.
19 Xin RL, Leng Y, Wang N. In situ TEM examinations of octacalcium phosphate to hydroxyapatite transformation [J]. Journal of Crystal Growth,2006,289:339-344.
20 Kim S, Ryu HS, Shin H, Jung HS, Hong KS. In situ observation of hydroxyapatite nanocrystal formation from amorphous calcium phosphate in calcium-rich solutions [J] Materials Chemistry and Physics,2005,91:500-506.
1 Kang YQ, Yao YD, Yin GF, Huang ZB, Liao XM, Xu XJ, Zhao GX. A study on the in vitro degradation properties of poly(1-lactic acid)/β-tricalcuim phosphate(PLLA/(3-TCP) scaffold under dynamic loading [J]. Europen Journal of Cardiovascular Prevention & Rehabilitation,2009,31:589-594
2 Kang YQ, Xu XJ, Yin GF, Chen AZ, Liao L, Yao YD, Huang ZB, Liao XM. A comparative study of the in vitro degradation of poly(1-1actic acid)/β-tricalcium phosphate scaffold in static and dynamic simulated body fluid [J]. European Polymer Journal,2007, 43:1768-1778.
3 邓春林.Ca-P生物陶瓷表面类骨磷灰石的形成、机理及其成骨性能研究[D].四川大学博士学位论文,2004,06.
4 Xiao GY, Lu YP, Zhu RF, Li ST, Wang AJ. Effect of post-deposition heat treatment on mechanical properties of thermally sprayed HA coating [J]. Surface Engineering,2008, 24:307-312.
5 Joseph NJ, Lakshmi S, Jayakrishnan A. A floating-type oral dosage form for piroxicam based on hollow polycarbonate microspheres:in vitro and in vivo evaluation in rabbits [J]. Journal of Controlled Release,2002,79:71-79.
6 Tadashi K, Hiroaki T. How useful is SBF in predicting in vivo bone bioactivity [J]? Biomaterials,2006,27:2907-2915.
7 段友容,姚喆,王朝元,陈继镛,张兴栋.多孔磷酸钙陶瓷在动态SBF中类骨磷灰石形成的研究[J].生物医学工程学杂志,2002,19：365-369.
8 Pierre L, Atsuo I, Tetsuya T. Sol-Gel Synthesis of Amorphous Calcium Phosphate and Sintering into Microporous Hydroxyapatite Bioceramics [J]. Journal of the American Ceramic Society,1998,81:1421-1428.
9 Suzanne HM, Joseph PZ, Michael GD. In vitro evaluation of amorphous calcium phosphate and poorly crystallized hydroxyapatite coatings on titanium implants [J]. Journal of Biomedical Materials Research,1993,27:111-117.
10 Masahisa N, Takashi N, Tadashi K, Masami T, Masaki O. Differences of bone bonding ability and degradation behaviour in vivo between amorphous calcium phosphate and highly crystalline hydroxyapatite coating [J]. Biomaterials,1996,17:1771-1777
11 Juhasz JA, Best SM, Auffret AD, Bonfield W. Biological control of apatite growth in simulated body fluid and human blood serum [J]. Journal of Materials Science:Materials in Medicine,2008,19:1823-1829.
12 Ugur T, Mustafa G. The effect of surface treatment on CaP deposition of Ti6Al4V open cell foams in SBF solution [J]. Ceramics International,2010,36:1805-1816.
13 Xiao GY, Lu YP, Zhu RF, Wang AJ. Effect of heat treatment on performance of hydroxyapatite coatings immersed in simulated body fluid [J]. Surface Engineering,2009, 25:136-140.
14孙瑞雪.多孔及空心羟基磷灰石微球的制备与表征[D].山东大学博士毕业论文,2006.
15 Mizushima Y, Ikoma T, Tanaka J, Hoshi K, Ishihara T, Ogawa Y, Ueno A. Injectable porous hydroxyapatite micropraticles as a new carrier for protein and lipophilic drugs [J]. Journal of Controlled Release,2006,110:260-265.
16 Kim HM, Himeno T, Kokubo T, Nakamura T. Process and kinetics of bonelike apatite formation on sintered hydroxyapatite in a simulated body fluid [J]. Biomaterials,2005,26: 4366-4373.
17李明欧,肖秀峰,刘榕芳.含锌羟基磷灰石的水热合成与结构表征[J].硅酸盐学报,2008，36：378-382.
18 Yu XH, Qu HB, Knech DAT, Wei M. Incorporation of bovine serum albumin ratio biomimetic coatings on titanium with high loading efficacy and its release behavior [J]. Journal of Materials Science:Materials in Medicine,2009,20:287-294.
19 Valeria M, Carlo C, Antonio E, Antonella G, Filippo P, Maurizio L. Aggregation kinetics of bovine serum albumin studied by FTIR spectroscopy and light scattering [J]. Biophysical Chemistry,2004,107:175-187.
20 Tatsuo M, Shinji K, Mitsutoshi N, Hiroshi N, Thomas PA, Atsushi S, Kazumi S. FT-IR analysis of BSA fouled on ultrafiltration and microfiltration membranes [J]. Journal of Membrane Science,2001,192:201-207.
21 Liu TY, Chen SY, Liu DM, Liou SC. On the study of BSA-loaded calcium-deficient hydroxyapatite nano-carriers for controlled drug delivery [J]. Journal of Controlled Release,2005,107:112-121.
22 Arvind S, Suprabha N, Archana A, Debasish B, Patcha R. Synthesis of Nanosized and Microporous Precipitated Hydroxyapatite in Synthetic Polymers and Biopolymers [J]. Journal of the American Ceramic Society,2003,86:357-359.
23刘艳.羟基磷灰石吸附有机物质的研究[D].济南大学硕士学位论文,2005,06.
24叶青.羟基磷灰石与牛血.清白蛋白相互作用的原位ATR-FTIR及EQCM研究[D].厦门大学硕士学位论文,2006,06.
25 Takagi O, Kuramoto N, Ozawa M, Suzuki S. Adsorption/desorption of acidic and basic proteins on needle-like hydroxyapatite filter prepared by slip casting [J]. Ceramics International,2004,30:139-143.
26 Yin G, Liu, Zhan J, Ding FX, Yuan NJ. Impacts of the surface charge property on protein adsorption on hydroxyapatite [J]. Chemical Engineering Journal,2002,87:181-186.
27 Kandori K, Fudo A, Ishikawa T. Study on the particle texture dependence of protein adsorption by using synthetic micrometer-sized calcium hydroxyapatite particles [J]. Colloids and Surfaces B:Biointerfaces,2002,24:145-153.
28 Ouizat S, Barroug1 A, Legrouri A, Rey C. Adsorption of bovine serum albumin on pooly crystalline apatite:influence of maturation [J]. Materials Research Bullitin,1999,34: 2279-2289.
29 Ogawa T, Yokoo A, Naganuma K, Fujinuma S, Kawamura K. Porous particles of calcium phosphate compound and production process thereof [P]. US Patent,5158756 (1990).
30 Liu YL, Hunziker EB, Layrolle P, De Bruijn JD, De Groot K. Bone Morphogenetic Protein 2 Incorporated into Biomimetic Coatings Retains Its Biological Activity [J]. Tissue Engineering,2004,10:101-108.
31 Luong NL, Sun IH, Patel RJ, Mark E. Outslay, David H. Kohn. Spatial control of protein within biomimetically nucleated mineral [J]. Biomaterials,2006,27:1175-1186.
32 Diana T. Hughes W, Rachel CH, Graham E. Adsorption of bovine serum albumin onto hydroxyapatite [J]. Biomaterials,1995,16:697-702.
33 Chou YF, Chiou WA, Xu YH, Dunn JCY, Wu BM. The effect of pH on the structural evolution of accelerated biomimetic apatite [J]. Biomaterials,2004,25:5323-5331.
34 Liu Y, De Groot K, Hunziker EB. Osteoinductive Implants:The Mise-en-scene for Drug-Bearing Biomimetic Coatings [J]. Annals of Biomedical Engineering,1994,32: 398-406.
35 Hing KA, Best SM, Tanner KE, Bonfield W, Revell PA. Quantification of bone ingrowth within bone-derived porous hydroxyapatite implants of varying density [J]. Journal of Materials Sciece:Materials Medicine,1999,10:663-670.
36 Ayers RA, Wolford LM, Bateman TA, Ferguson VL, Simske SJ. Quantification of bone ingrowth into porous block hydroxyapatite in humans [J]. Journal of Biomedical Materials and Research,1999,47:54-59.
37 Hing AK, Best SM, Tanner KE, BonfieldW, Revell PA.Mediation of bone ingrowth in porous hydroxyapatite bone graft substitutes [J]. Journal of Biomedical Materials and Research,2004,68A:187-200.
38 Gutierres M, Lopes MA, Hussain NS, Lemos AF, Ferreira JMF, Afonso A, Cabral AT, Almeida L, Santos JD. Bone ingrowth in macroporous Bonelike for orthopaedic applications [J]. Acta Biomaterialia,2008,4:370-377.
39 Lopes MA, Knowles JC, Santos JD, Monteiro FJ, Olsen I. Direct and Indirect effects of P2O5-glass reinforced-hydroxyapatite composites and growth and function of osteoblast-like cells [J]. Biomaterials,2000,21:1165-1172.
40 Lobato JV, Hussain NS, Botelho CM, et al. Titanium dental implants coated with Bonelike: clinical case report [J]. Thin Solid Films,2006,515:279.
41 Lopes MA, Santos JD,Monteiro FJ, Ohtsuki C, Osaka A, Kaneko S. Push-out testing and histological evaluation of glass reinforced hydroxyapatite composites implanted in the tibiae of rabbits [J]. Journal of Biomedicla Materials and Research,2001,54:463-469.
42 Koshino T, Murase T, Saito T. Medial opening-wedge high tibial osteotomy with use of porous hydroxyapatite to treat medial compartment osteoarthritis of the knee [J]. Journal of Bone and Joint Surgery-American,2003,85:78-85.
43 Gauthiera O, Boulerb JM, Aguadoa E, Piletb P, Daculsi G. Macroporous biphasic calcium phosphate ceramics:influence of macropore diameter and macroporosity percentage on bone ingrowth [J]. Biomaterials,1998,19:133-139.
44 Lia LH, Kommareddy KP, Pilz C, Zhou CR, Fratzl P, Manjubala I. In vitro bioactivity of bioresorbable porous polymeric scaffolds incorporating hydroxyapatite microspheres [J]. Acta biomateriala,2010,6:2525-2531.
1 Braddock M, Houston P, Campbell C, Ashcroft P. Born again bone:tissue engineering for bone repair [J]. News in Physiological Sciences,2001,16:208-213.
2 Goldberg VM, Stevenson S. Natural history of autografts and allografts [J]. Clinical Orthopaedics and Related Research,1987,225:7-16.
3 Costantino PD, Friedman CD. Synthetic bone graft substitutes [J]. Otolaryngologic Clinics of North America,1994,27:1037-1074.
4 Ma PX. Biomimetic materials for tissue engineering [J]. Advanced Drug Delivery Review, 2008,60:184-198.
5 Shin H, Jo S, Mikos AG. Biomimetic materials for tissue engineering [J]. Biomaterials, 2003,24:4353-4364.
6 Hay ED. Extracellular-matrix [J]. Journal of Cellular Biochemistry,1981,91:205-223.
7 Lutolf MP, Hubbell JA. Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering [J]. Natature Biotechnology, 2005,23:47-55.
8 LeGeros RZ. Properties of osteoconductive biomaterials:calcium phosphates [J]. Clinical Orthopaedics and Related Research,2002,395:81-98.
9余耀庭,张兴栋.生物医用材料[M].天津：天津大学出版社,2000：1-2.
10崔福斋,冯庆玲.生物材料学[M].北京：清华大学出版社,2004：1-2.
11 Akao M, Aoki H, Kato K. Mechanical properties of sintered hydroxyapatite for prosthetic applications [J]. Journal of Materials Science,1981,16:809-812.
12 Yoshikawa T, Ohgushi H, Nakajima H, Yamada E, Ichijima K, Tamai S. In vivo osteogenic durability of cultured bone in porous ceramics:a novel method for autogenous bone graft substitution [J]. Transplantation,2000,69:128-134.
13 De With G, Van Dijk HJA, Hattu N, Prijs K. Preparation, microstructure and mechanical properties of dense polycrystalline hydroxyapatite [J]. Journal of Materials Science,1981, 16:1592-1598.
14 Ma PX, Zhang RY. Microtubular architecture of biodegradable polymer scaffolds [J]. Journal of Biomedical Materials Research,2001,56:469-477.
15 Chen VJ, Ma PX. The effect of surface area on the degradation rate of nano-fibrous poly(L-lactic acid) foams [J]. Biomaterials,2006,27:3708-3715.
16 Ma PX, Zhang R. Synthetic nano-scale fibrous extracellular matrix [J]. journal of bone and mineral research,1999,46:60-72.
17 Woo KM, Wei GB, Ma PX. Enhancement of fibronectin-and vitronectin-adsorption to polymer/hydroxyapatite scaffolds suppresses the apoptosis of osteoblasts [J]. Journal of Bone and Mineral Research 2002,17:M49.
18 Wei GB, Ma PX. Structure and properties of nano-hydroxyapatite/polymer composite scaffolds for bone tissue engineering [J]. Biomaterials,2004,25:4749-4757.
19 Zhang RY, Ma PX. Biomimetic Polymer/Apatite Composite Scaffolds for Mineralized Tissue Engineering [J]. Macromelecular bioscience,2004,4:100-111.
20 Ma PX, Zhang R, Xiao GZ, Franceschi R. Engineering new bone tissue in vitro on highly porous poly(alpha-hydroxyl acids)/hydroxyapatite composite scaffolds [J]. Journal of Biomedical Materials Research,2001,54:284-293.
21 Langer R, Vacanti JP. Tissue engineering [J]. Science,1993,260:920-926.
22 Mikos AG, Thorsen AJ, Czerwonka LA, Bao Y, Langer R, Winslow DN, Vacanti JP. Preparation and characterization of poly(1-lactic acid) foams [J]. Polymer,1994,35: 1068-1077.
23 Whang K, Thomas CH, Healy KE, Nuber G. A novel method to fabricate bioabsorbable scaffolds [J]. Polymer,1995,36:837-842.
24 Mooney DJ, Baldwin DF, Suh NP, Vacanti JP, Langer R. Novel approach to fabricate porous sponges of poly(d,1-lactic-co-glycolic acid) without the use of organic solvents [J]. Biomaterials,1996,17:1417-1422.
25 Borden M, Attawia M, Laurencin CT. The sintered microsphere matrix for bone tissue engineering:in vitro osteoconductivity studies [J]. Journal of Biomedical Materials Research,2002,61:421-429.
26 Wintermantel E, Mayer J, Blum J, Eckert KL, Luscher P, Mathey M. Tissue engineering scaffolds using superstructures [J]. Biomaterials,1996,17:83-91.
27 Chen VJ, Laura AS, Ma PX. Bone regeneration on computer-designed nano-fibrous scaffolds [J]. Biomaterials,2006,27:3973-3979.
28 Wei GB, Ma PX. Macroporous and nanofibrous polymer scaffolds and polymer/bone-like apatite composite scaffolds generated by sugar spheres [J]. J Biomed Mater Res,2006, 78A:306-315.
29 Hu J, Feng K, Liu XH, Ma PX. Chondrogenic and osteogenic differentiations of human bone marrow-derived mesenchymal stem cells on a nanofibrous scaffold with designed pore network [J]. Biomaterials,2009,30:5061-5067.
30 Laura AS, Liu XH, Hu J, Ma PX. The influence of three-dimensional nanofibrous scaffolds on the osteogenic differentiation of embryonic stem cells [J]. Biomaterials,2009, 30:2516-2522.
31 Woo KM, Jun JH, Chen VJ, Seo J, Baek JH, Ryoo HM, Kim GS, Somerman JM, Ma PX. Nano-fibrous scaffolding promotes osteoblast differentiation and biomineralization [J]. Biomaterials,2007,28:335-343.
32 Woo KM, Seo J, Zhang RY, Ma PX. Suppression of apoptosis by enhanced protein adsorption on polymer/hydroxyapatite composite scaffolds [J]. Biomaterials,2007,28: 2622-2630.
33 Jiao YP, Liu ZH, Cui FZ, Zhou CR. Effect of Hydrolysis Pretreatment on the Formation of Bone-like Apatite on Poly(L-lactide) by Mineralization in Simulated Body Fluids [J]. Journal of Bioactive and Compatible Polymers,2007,22:492-507.
34 Yoshiro Y, Ayako O, Atsuo I. Biomimetic coating of an apatite layer on poly(1-lactic acid); improvement of adhesive strength of the coating [J]. Journal of Materials Science: Materials in Medicine,2007,18:1727-1734.
35 Niu XF, Feng QL, Wang MB, Guo XD, Zheng QX. Porous nano-HA/collagen/PLLA scaffold containing chitosan microspheres for controlled delivery of synthetic peptide derived from BMP-2 [J]. Journal of Controlled Release,2009,134:111-117.
36 Saito N, Murakami N, Takahashi J, Horiuchi H, Ota H, Kato H, Okada T, Nozaki K, Takaoka K, Synthetic biodegradable polymers as drug delivery systems for bone morphogenetic proteins[J]. Advanced Drug Delivery Reviews,2005,57:1037-1048.
37 Hu DS, Liu HJ, Pan IL. Inhibition of bovine serum albumin adsorption by poly (ethylene glycol) soft segment in biodegradable poly(ethylene glycol)/poly(L-lactide) copolymers [J]. Journal of Applied Polymer Science,1993,50:1391-1396.
38 Webster TJ, Ergun C, Doremus RH, Siegel RW, Bizios R. Specific proteins mediate enhanced osteoblast adhesion on nanophase ceramics [J]. Journal of Biomedical Materials Research,2000,51:475-483.
39 Webster TJ, Siegel RW, Bizios R. Osteoblast adhesion on nanophase ceramics [J]. Biomaterials,1999,20:1221-1227.
40 Yamada KM. Cell surface interactions with extracellular materials [J]. Annual Review of Biochemistry,1983,52:761-799.
41 Boal D. Machanics of the cell [M]. Cambridge University Press,2002.
1. S. V. Dorozhkin, M, Epple, Angew. Chem. Int. Ed.,2003,41,3130.
2. K.A. Khor, Y.W. Gu, C.H. Quek, P. Cheang, Surf. Coat. Tech.,2003,168,195.
3. G. Bezzi, G. Celotti, E. Landi. T.M.G. La Torretta, I. Sopyan, A. Tampieri, Mater. Chem. Phys.,2003,78, 816.
4. L.L. Hench, J. Wilson, Science,1984,226,630.
5. J. M. Gomez-Vega, E, Saiz, A.P. Tomisa, G.W. Marshall, S. J. Marshall, Biomaterials,2000,21,105.
6. Luo P, Nieh TG, Biomaterials,1996,17,1959.
7. Luo P, Nieh TG, Mater. Sci. Eng. C,1995,3,75.
8. Bertranda G, Roya P, Filiatreb C, Coddeta C, Chem. Eng. Sci.,2005,60,95.
9. Dyshlovcnko S, Pawlowski L, Roussel P, Muranob D, Maguer AL, Surf. Coat. Tech.,2006,200,3845.
10. Sun RX, Lu YP, Li MS, Li ST, Zhu RF, Surf. Coat. Tech.,2005,190,281.
11. Emily K. Cushnie, Yusuf M. Khan, Cato T. Laurencin, J. Biomed. Mater. Res.,2008,84A,54.
12. Vladimir S. K, Serguei MB, Elena VK, Biomaterials,2002,23,3449.
13.Allal B, Etienne L, Jacques L, Paul GR, J. Colloid. Interf. Sci.,1998,208,147.
14. Paul W, Nesamony J, Sharma CP, Technical Note,2001,12,660.
15. Shuji S, Kiminori A, Keijiro F, United States Patent 5,009,898.
16. Starling LB, Stephan JE, United States Patent 6,358,532.
17. A. S. Posner, F. Betts, Ace. Chem. Res.,1975,8,273.
18. E. D. Eanes, Gillesse I. H., A. S. Posner, Nature,1965,208,365.
19. M. Nagano, T. Nakamura, T. Kokubo, M. Tanahashi, M. Ogawa, Biomaterials,1996,17,1771.
20. S.H. Maxian, J.P. Zawadsky, M.G. Dunn, J. Biomed. Mater. Res.,1993,27,717.
21. R.J. Dekker, C.A. Van Blitterswijk, J.D. De Bruijn, M. Stigter, F. Barrere, P. Layrolle, Biomaterials, 2005,26,5231.
22. D. Skrtic, J.M. Antonucci, E.D. Eanes, R.T. Brunworth, J. Biomed. Mater. Res.,2002,59,597.
23. D. Hakimimehr, D.M. Liu, T. Troczynski, Biomaterials,2005,26,7297.
24. R.Z. Legeros, S. Lin, R. Rohanizadeh, D. Mijares, J.P. Legeros, J. Mater. Sci.:Mater. Med.,2003,14, 201.
25. S. Sadasivan, D. Khushalani, S. Mann, Chem. Mater.,2005,17,2765.
26. P. Layrolle, A. Lebugle, Chem. Mater.,1996,8,134.
27. P. Layrolle, A. Ito, T. Tateishi, J. Am. Ceram. Soc.,1998,81,1421.
28. Sebti S, Solhy A, Tahir R, Smahi A, Appl Catal A:Gen,2002,235,273.
29. Chen Shaoqiang, Zhu Ziqiang, Zhu Jianzhong, Appl. Surf. Sci.,2004,230,418.
30. L.M. RodrmH guez-Lorenzo, M. Vallet-RegmH, J.M.F. Ferreira, Biomaterials,2001,22,583.
31. Yanbao Li, Tjandra Wiliana, Kam C. Tam, Mater. Res. Bull.,2007,42,820.
32. Sujin Kim, Hyun-Seung Ryu, Hyunho Shin, Mater. Chem. Phys.,2005,91,500.
33. D. Tadic, F. Peters, M. Epple, Biomaterials,2002,23,2553.
34. Senya Inoue, Akira Ono, Nobuyuki Otaki, US patent 5,205,928.
35. Ruixue Sun, Yupeng Lu, Kezheng Chen, Mater. Sci. Eng. C,2009,29,1088.