多孔磷酸钙陶瓷在动态SBF中类骨磷灰石形成的研究

本实验在模拟体液（SBF）以静止、等于或大于骨骼肌组织内体液正常生理流率（2ml/100ml.min)的流动条件下，研究多孔磷酸钙陶瓷上类骨磷灰石的形成，结果表明，SBF在生理流率（2ml/100ml.min)情况下，材料仅在多孔磷酸钙陶瓷孔隙内部形成类骨磷灰石，静态（0ml/100ml.min)情况下，多孔磷酸钙陶瓷材料表面有类骨磷灰石形成；高于生理流率（10ml/100ml/min)时，表面和断面均无类骨磷灰石形成，但如果增加SBF中的Ca^2 ,HPO4^2-的浓度，则在孔隙内部有类骨磷灰石形成，生理流条件下的结果与多数肌肉内植入磷酸钙陶瓷试验的结果一致。仅在多孔材料内部成骨，这个结果表明，比起通常使用的静态浸泡试验，SBF以生理流率流动的动态体外试验能够更好地模拟类骨 磷灰石生长的体内环境，动态SBF对了解类骨磷灰石形成，进而了解磷酸钙陶瓷在体内诱导成骨机理是十分有用的。     

在不同动物肌肉中磷酸钙陶瓷表面类骨磷灰石的形成研究

磷酸钙陶瓷材料植入动物体内后其表面类骨磷灰石层的形成对骨的形成有非常重要的作用，并被认为是骨诱导发生的先决条件。我们将相同大小的孔壁有微孔的多孔材料和致密磷酸钙陶瓷材料植入猪，狗、兔和鼠的背肌或腿肌内，研究陶瓷表面类骨磷灰石的形成，以了解类骨磷灰石层的形成与骨诱导的联系。结果表明：磷酸钙陶瓷材料植入动物的肌肉内14d后，狗，兔和鼠体内的多孔材料孔隙内表面（包括陶瓷表面较深孔隙）有一层类骨磷灰石层形成；植入猪体内的多孔材料内外表面都形成了一层类骨磷灰石，致密材料在几种动物体内都未观察到类骨磷灰石层形成，类骨磷灰石层形成的快慢次序与动物组织学观察到的在不同动物的肌内骨诱导性高低的次序不一致。证实了类骨磷灰石层的形成的确是骨诱导的先决条件。但还有其它因素影响骨诱导的发生。     

仿生浸泡对碳酸根掺杂的钙磷生物陶瓷表面的影响

钙磷生物陶瓷表面类骨磷灰石层的形成对其诱导新骨生成起非常重要的作用。为了研究碳酸根掺杂的钙磷生物陶瓷其表面类骨磷灰石层形成的能力,利用体外模拟装置首次研究了碳酸根掺杂的钙磷生物陶瓷材料在仿生浸泡的过程其表面的类骨磷灰石层形成的变化。结果表明,钙磷生物陶瓷因有CO3^2-的存在,导致该材料形成类骨磷灰石晶体的时间大大提前。并且在-βTCP含量较低的相组成下（HA/-βTCP之比为9/1）,该陶瓷在与模拟体液（SBF）作用较短的时间内（约9d）就能形成类骨磷灰石晶体。而不含CO3^2-的钙磷生物陶瓷却只能与SBF液作用较长时间（约14d）才开始形成类骨磷灰石晶体。在相同的作用时间内,含CO3^2-的钙磷生物陶瓷所形成的类骨磷灰石晶体的情况远远优于不含CO3^2-的钙磷生物陶瓷。此外,还有部分的缺钙羟基磷灰石晶体的形成。钙磷生物陶瓷中CO3^2-的掺杂引入,有利于该材料生物活性的提高,进而有利于骨缺损的快速修复。     

炎性历程模拟体液对多孔HA/β-TCP生物陶瓷类骨磷灰石形成的影响

通过对多孔 HA/β- TCP生物陶瓷在炎性历程模拟体液 (Sim ulated body fluid,SBF)中动态浸泡 (即先在模拟炎性体液 p H6 .5的 SBF中动态浸泡 2 d,再在正常体液 p H7.4的 SBF中动态浸泡 12 d)的类骨磷灰石形成情况的研究后发现 ,模拟炎性历程的微酸性会溶解材料表面颗粒较细或曲率半径较小的部分 ,使材料表面变得光滑和溶解性能下降 ,在随后正常体液的 p H值下类骨磷灰石的形成量明显减少 ,这为理解钙磷生物陶瓷植入体内的诱导成骨机理和在体外筛选骨诱导性较好的钙磷材料提供了更可靠的方法。另外 ,实验结果还显示 ,用微波等离子体烧结的多孔 HA/β- TCP生物陶瓷 ,在正常 SBF和模拟了炎性历程的 SBF的动态实验中 ,其类骨磷灰石形成情况都好于用常规马弗炉烧结的样品 ,这预示用微波等离子体烧结的多孔 HA/β- TCP生物陶瓷可能具有更好的骨诱导活性。     

激光气体氮化改性NiTi形状记忆合金

为了提高生物医用材料NiTi形状记忆合金的生物活性，采用高功率连续波Nd：YAG激光辐照，在置于N，反应室中的NiTi形状记忆合金表面制备TiN激光改性层，考察改性层在37℃模拟人体体液SBF溶液中类骨磷灰石的形成能力。采用扫描电子显微镜、X射线能量损失谱仪、傅立叶转换红外光谱仪研究和分析样品表面沉积层的组织形貌、成分及沉积物的结构随沉积时间的变化规律，进而探讨激光改性层表面类骨磷灰石沉积层的形成过程。实验结果表明，激光气体氮化可显著改善NiTi形状记忆合金在体外模拟环境条件下诱导类骨磷灰石沉积的能力，其在37℃SBF溶液中沉积物成分与人体内磷灰石成分接近，Ca、P摩尔比为1．57。     

模拟体液中生物大分子对类骨磷灰石矿化的影响

为考察体内生物大分子对羟基磷灰石（hydroxyapatite,HA）基底表面矿化物形成的影响,将牛血清白蛋白（bovine serum albumin,BSA）和硫酸软骨素（chondroitin sulfate,CS）大分子分别浸入模拟体液（SBF）中制备成2种矿化介质,再将HA浸入上述矿化介质中3d观察类骨磷灰石形成过程.结果 发现HA基底表面均沉积有Na＋和CO2-3取代的类骨磷灰石（Ca3.78Na0.02）（Ca5.22Na0.48）（CO3）1.5（OH）.BSA在2SBF中的存在促进了类骨磷灰石晶体在基材表面沉积,有利于其沿（300）晶面择优取向生长.CS对类骨磷灰石晶体的生长呈阻碍作用,获得的晶粒尺寸较小.模拟体液中BSA和CS大分子对类骨磷灰石晶体生长和形貌等均有一定的作用.     

亚微米拓扑结构磷酸三钙陶瓷的研制及骨诱导性能

背景：人工合成的磷酸钙陶瓷材料与天然骨组织无机成分相似,通过表面形貌和化学组成进行功能化设计可赋予其优异的骨传导和骨诱导性能,研发具有骨诱导性能的磷酸钙陶瓷材料是目前的研究热点。目的：通过材料形貌调控和功能化设计赋予亚微米拓扑结构磷酸三钙陶瓷骨诱导性能,检测其理化性能及骨诱导性能。方法：采用高温烧结法制备亚微米拓扑结构的磷酸三钙陶瓷,以市场可供商品化的骨修复材料Bio-Oss骨粉为对照组,表征两种材料的表面形貌、蛋白吸附能力及体外矿化性能。将第3代人牙周膜干细胞与两种材料浸提液共培养,采用CCK-8法检测细胞增殖,茜素红染色检测细胞矿化性能;将第3代人牙周膜干细胞分别接种至两种材料表面,采用碱性磷酸酶染色检测早期成骨,qR T-PCR检测成骨相关因子的表达。结果与结论：(1)扫描电镜下可见两种材料均具有颗粒状纹理的微孔表面,Bio-Oss颗粒明显小于磷酸三钙陶瓷,两种材料的总孔隙度、大孔隙度和微孔隙度相似,磷酸三钙陶瓷主要为亚微米级孔隙,晶粒粒径100 nm-1.0μm,Bio-Oss骨粉主要为纳米级孔隙;体外矿化实验显示,磷酸三钙陶瓷表面诱导骨磷灰石沉积的能力强于Bio-Oss骨粉;...     

结构特征对磷酸钙陶瓷骨诱导活性的影响

背景：目前关于磷酸钙陶瓷诱导成骨的机制尚不完全清楚,许多学者试图从材料的结构特征方面去阐明磷酸钙陶瓷诱导成骨的机制。 目的：综述结构特征如何影响磷酸钙陶瓷的骨诱导活性。 方法：使用计算机检索PubMed和谷歌学术数据库中1997年1月至2015年3月关于磷酸钙骨组织工程的文献,排除观点陈旧和重复的文章,最后对60篇文章进行归纳总结。 结果与结论：磷酸钙陶瓷的结构可分宏观结构和微观结构,宏观结构包括宏孔、孔洞或管道及颗粒间的间隙等;微观结构包括微孔、颗粒大小、表面粗糙度、比表面积等。结构特征的中各个参数都以一定的方式影响磷酸钙陶瓷的生物活性,使其诱导成骨能力发生着从无到有、从弱到强的变化。但是骨诱导活性的优化并非仅仅依靠结构设计就能达到目的,因为磷酸钙陶瓷的物理化学性质同样也会影响其在体内的生物活性。因此,磷酸钙陶瓷结构设计需要“因地制宜”地与其自身的物理化学性质“完美契合”,以获得最佳的骨诱导活性。 中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

骨诱导性双相磷酸钙陶瓷的研究与应用

背景：双相磷酸钙陶瓷是由羟基磷灰石和β-磷酸三钙两相成分构成的陶瓷,其化学组成与骨组织的无机成分相似,目前体内外研究表明双相磷酸钙陶瓷除具有良好的生物相容性、生物活性、骨传导性以外,还具有骨诱导性,因此有望成为理想的骨替代材料。然而,双相磷酸钙陶瓷骨诱导的影响因素及相关机制尚不明确。 目的：综述影响双相磷酸钙陶瓷骨诱导性的因素及机制。 方法：应用计算机检索Ovid Medline和PubMed数据库中1985年1月至2013年1月关于双相磷酸钙陶瓷骨诱导性的文章,在标题和摘要中以“bone graft substitutes, biphasic calcium phosphates, osteoinduction”为检索词进行检索。选择文章内容与双相磷酸钙陶瓷的骨诱导性有关者,同一领域文献则选择近期发表或发表在权威杂志的文章,最终选择34篇文献进行综述。 结果与结论：综合相关文献发现双相磷酸钙陶瓷的化学组成通过影响钙磷的降解和再沉积速率,进而影响其骨诱导性的发挥;同时双相磷酸钙陶瓷的物理结构通过影响骨形成相关蛋白的吸附、血管生成、组织长入、局部微环境并进一步诱发干细胞的骨向分化来影响双相磷酸钙陶瓷的骨诱导性;另外双相磷酸钙陶瓷植入动物的种属,植入部位及植入体大小也可对其骨诱导性产生影响。因此通过对双相磷酸钙陶瓷骨诱导性影响因素及相关机制的研究可为制备具有稳定骨诱导性的骨替代材料提供依据。     

原位法制备羟基磷灰石/聚乳酸纳米复合材料的体外生物学研究

通过羟基磷灰石/聚乳酸(HA/PLLA)纳米复合材料在模拟体液(SBF)中的浸泡实验评价该材料的生物学性能。测试发现HA/PLLA纳米复合材料在浸泡过程中SBF的pH值呈现下降趋势,HA的存在缓冲了PLLA的酸性;复合材料表面有类骨磷灰石层沉积,并有"蚕茧状"类骨磷灰石颗粒和夹有短棒状晶体的片状晶体簇生成;同时复合材料的降解导致表面形成大量蜂巢状多孔。因此原位法制备的HA/PLLA纳米复合材料具有较好的生物活性和可降解性。     

Surface reactions of calcium phosphate ceramics to various solutions

The surface reactions of calcium phosphate ceramics have been thought to play an important role in bonding with living bone. Hydroxyapatite (HA), tricalcium phosphate (TCP), and two kinds of apatite-containing glass ceramics were immersed in three types of solutions with different chemical constituents. The first solution was a physiological saline, the second contained phosphate (PO4), and the third was a balanced salt solution consisting of calcium (Ca), magnesium (Mg), and PO4. After serial incubation periods, changes in the solutions were assessed by measurement of total Ca, Mg, and PO4. The ceramic surfaces were studied using scanning electron spectroscopy, infrared reflection spectroscopy, and thin-film x-ray diffraction. The surface reactions of the ceramics were greatly affected by the chemical compositions of the surrounding media. In the complete solution with both Ca and PO4, a carbonated apatite layer was formed on the surfaces of HA, TCP, and the glass ceramics. In comparison to HA and TCP, the glass ceramics were characterized as Ca-releasing materials, the dissolved Ca creating an apatite layer on the surfaces in a few days, in conjunction with PO4 stock in the surrounding media. The immersion test with various solutions proved to be a simple and effective method of assessing surface conditions of ceramic materials.     

Mechanism of bonelike apatite formation on bioactive tantalum metal in a simulated body fluid.

Development of tantalum metal with bone-bonding ability is paid much attention because of its attractive features such as high fracture toughness, high workability and its achievement on clinical usage. Formation of bonelike apatite is an essential prerequisite for artificial materials to make direct bond to living bone. The apatite formation can be assessed in vitro using a simulated body fluid (SBF) that has almost equal compositions of inorganic ions to human blood plasma. The present authors previously showed that the apatite formation on tantalum metal in SBF was remarkably accelerated by treatment with NaOH aqueous solution and subsequent firing at 300 degrees C, while untreated tantalum metal spontaneously forms the apatite after a long soaking period. The purpose of the present study is to clarify the reason why the NaOH and heat treatments accelerate the apatite formation on tantalum metal. X-ray photoelectron spectroscopy was used to analyze changes in surface structure of the tantalum metal at an initial stage after immersion in SBF. Untreated tantalum metal had tantalum oxide passive layer on its surface, while amorphous sodium tantalate was formed on the surface of the tantalum metal by the NaOH and heat treatments. After soaking in SBF, the untreated tantalum metal sluggishly formed small amount of Ta-OH groups by a hydration of the tantalum oxide passive layer on its surface. In contrast, the treated tantalum metal rapidly formed Ta-OH groups by exchange of Na+ ion in the amorphous sodium tantalate on its surface with H3O+ ion in SBF. Both the formed Ta-OH groups combined with Ca2+ ion to form a kind of calcium tantalate, and then with phosphate ion, followed by combination with large amount of Ca2+ ions and phosphate ions to build up apatite layer. The formation rate of Ta-OH groups on the treated tantalum metal predominates the following process including adsorption of Ca2+ ion and phosphate ion on the surface. It is concluded that the acceleration of the apatite nucleation on the tantalum metal in SBF by the NaOH and heat treatments was attributed to the fast formation of Ta-OH group, followed by combination of the Ta-OH groups with Ca2+ and phosphate ions.     

The influence of X-ray radiation on the mineral/organic matrix interaction of bone tissue: an FT-IR microscopic investigation

Fourier transform infrared microscopy was used to investigate human cortical bone samples before and after treatment with increasing doses of X-ray radiation. Especially the spectral region of the v1 and v3 phosphate vibrations of hydroxyapatite, the main mineral component of bone, and the region of the amide I and amide II vibrational bands due to the collagen extracellular matrix were examined. Major spectral changes in the phosphate region between 1250-1000 cm(-1) occur after irradiation doses between 1 and 4 Gray. These findings are explained by a decrease in size of mineral crystallites and by variances of the toichiometric/non-stoichiometric apatite composition. The Ca2+ /PO4(3-) /HPO4(2-) composition in the biological apatite is altered near the bone surface. The secondary structure of the collagen matrix is not affected by cumulative irradiation up to doses of 15 Gray as indicated by the unchanged frequency maximum and contour shape of the amide I band between 1600-1700 cm(-1) . However, side chain carboxylate groups of the collagen matrix that are involved in coordination with apatite bound calcium ions are partially removed by decarboxylation upon irradiation. Concomitantly, a loss of acidic phosphate groups due to a formation of phosphate groups with bound calcium is observed. These changes on a molecular level can be correlated with alterations in the mechanical properties of the bone samples, e.g. with an increased embrittlement as deduced from experiments with a scanning acoustic microscope.     

Porous calcium phosphate coating over phosphorylated chitosan film by a biomimetic method

A porous calcium phosphate coating deposited on chitosan films was studied using scanning electron microscopy, energy-dispersive X-ray analysis, micro-Fourier transform infrared spectroscopy (micro-FTIR) and thin-film X-ray diffractometry (XRD). Chitosan films were first prepared by dissolving chitosan powder in dilute acetic acid and drying in a flat petri dish. The films were phosphorylated using urea and H3PO4 with the P content being 0.1-0.2 wt%. Phosphorylated films soaked in saturated Ca(OH)2 solution for 8 days led to the formation of a calcium phosphate precursor phase over the entire surface. This precursor phase stimulated the growth of a porous coating of calcium-deficient hydroxy apatite when immersed in 1.5 x SBF for more than 20 days. Phosphorylated films not treated with Ca(OH)2 did not show any calcium phosphate growth upon immersion in SBF solution. The precursor phase is thought to be octacalcium phosphate, which nucleates a HAP phase during SBF treatment. Initially, this treatment in SBF results in the formation of a single-layer calcium phosphate particles over the film surface. As immersion time in SBF increases, further nucleation and growth produce a porous HAP coating. The Ca/P ratio of the HAP coating is a function of SBF immersion time.     

Mechanism and kinetics of apatite formation on nanocrystalline TiO2 coatings: a quartz crystal microbalance study

Apatite (Ca5(PO4)3OH) has long been considered as an excellent biomaterial to promote bone repairs and implant. Apatite formation induced by negatively charged nanocrystalline TiO2 coatings soaked in simulated body fluid (SBF) was investigated using in situ quartz crystal microbalance (QCM), scanning electron microscopy (SEM), Fourier-transformed infrared spectroscopy (FTIR), X-ray diffraction (XRD) and energy-dispersive X-ray spectroscopy (EDX) techniques, and factors affecting its formation such as pH, size of TiO2 particles and thickness of TiO2 coatings, were discussed in detail. Two different stages were clearly observed in the process of apatite precipitation, indicating two different kinetic processes. At the first stage, the calcium ions in SBF were initially attracted to the negatively charged TiO2 surface, and then the calcium titanate formed at the interface combined with phosphate ions, consequently forming apatite nuclei. After the nucleation, the calcium ions, phosphate ions and other minor ions (i.e. CO3(2-) and Mg2+) in supersaturated SBF deposited spontaneously on the original apatite coatings to form apatite precipitates. In terms of the in situ frequency shifts, the growth-rate constants of apatite (K1 and K2) were estimated, respectively, at two different stages, and the results were (1.96+/-0.14)x10(-3)s(-1) and (1.28+/-0.10)x10(-4)s(-1), respectively, in 1.5 SBF solution. It was found that the reaction rate at the first stage is obviously higher than that at the second stage.     

Calcium phosphate formation at the surface of bioactive glass in vitro

The calcium phosphate formation at the surface of bioactive glass was studied in vitro. Glass rods and grains were immersed in different aqueous solutions and studied by means of scanning electron microscopy and energy dispersive x-ray analysis. Surface morphological changes and weight loss of corroded grains were monitored. In-depth compositional profiles were determined for rods immersed in the different solutions. The solutions used were tris-buffer (tris-hydroxymethylaminomethane + HCl), tris-buffer prepared using citric acid (tris-hydroxymethylaminomethane + C6H8O7.H2O), and a simulated body fluid, SBF, containing inorganic ions close in concentration to those in human blood plasma. It was found that the calcium phosphate formation at the surface of bioactive glass in vitro proceeds in two stages. When immersing the glass in tris or in SBF a Ca,P-rich surface layer forms. This accumulation takes place within the silica structure. Later, apatite crystals forming spherulites appear on the surface. The Ca/P-ratio of initially formed calcium phosphate was found to be about unity. It is proposed that this is due to bonding of phosphate to a silica gel. The surface is stabilized, i.e., leaching is retarded, by the rapid Ca,P-accumulation within the silica structure before apatite crystals are observed on the surface. It is proposed that the initially formed calcium phosphate is initiated within the silica gel. The crystallizing surface provides nucleation sites for extensive apatite formation on the glass surface. In the presence of citrate no Ca,P-accumulation occur at the glass surface, but soluble Ca-citrate complexes form. By comparing the weight loss during corrosion in tris with that in the calcium and phosphate containing SBF, it is possible to establish whether the glass can induce apatite formation at its surface or not.     

Composition and structure of the apatite formed on PET substrates in SBF modified with various ionic activity products.

An apatite layer was formed on polyethyleneterephthalate (PET) substrates by the following biomimetic process. PET substrates were placed on granular particles of a CaO-SiO2-based glass in simulated body fluid (SBF) with ion concentrations nearly equal to those of human blood plasma to form apatite nuclei on their surfaces (first treatment). They then were soaked in modified SBFs, the ion concentrations of which were changed to give a variation in ionic activity product of apatite (IP), in order to make the apatite nuclei grow (second treatment). The Ca/P atomic ratio and the lattice constant c of the formed apatite decreased from 1.54 to 1.40 and from 6.880 to 6.838 A, respectively, with increasing ion concentrations from 0.75 to 2.00 times those of SBF, that is, with increasing IP from 10(-96.6) to 10(-91.9). This was attributed to an increase in the concentration of HPO4(2-) ion substituting for the PO4(3-) ion sites, which gave an increase in the Ca2+ in the apatite. Even the apatite formed in 1.00 SBF showed a Ca/P ratio of 1.51 and lattice constants a of 9.432 A and c of 6.870 A. The Ca/P ratio and lattice constant c were smaller and the lattice constant a was larger than those of the bone apatite; its Ca/P ratio and its lattice constants a and c, were 1.65, 9.419 A, and 6.88 A, respectively. This was attributed to the lower content (2.64 wt%) of the CO3(2-) ion substituting for the PO4(3-) ion sites of the apatite compared to that of the bone apatite (5.80 wt%). The lower content of the CO3(2-) ion in the apatite might be caused by the lower concentration of HCO3- ion in 1.00 SBF compared to that in human blood plasma.     

The role of surface functional groups in calcium phosphate nucleation on titanium foil: a self-assembled monolayer technique

Surface functional groups play important roles in nucleating calcium phosphate deposition on surgical titanium implants. In this study, various functional groups were introduced onto the surface of commercially pure titanium foils using a self-assembled monolayer (SAM) technique. An organic silane, 7-oct-1-enyltrichlorosilane (OETS) was used and -OH, -PO4H2, -COOH groups were derived from its unsaturated double bond. Ti foils were first oxidized in concentrated H2SO4/H2O2. ESCA and contact angle measurements were used to characterize the SAM surfaces and confirm the presence of various functional groups. A fast calcium phosphate deposition experiment was carried out by mixing Ca2+- and (PO4)(3-)-containing solutions in the presence of the surface-modified Ti samples at pH 7.4 at room temperature in order to verify the nucleating abilities of these functional groups. SEM, Raman spectroscopy, XRD and ATR-FTIR results showed that poorly crystallized hydroxyapatite (HA) can be deposited on the SAM surfaces with -PO4H2 and -COOH functional groups, but not onto the SAM with -CH=CH2 and -OH. -PO4H2 exhibited a stronger nucleating ability than that of -COOH. The oxidized Ti sample also showed some calcium phosphate deposition but to a lesser extent as compared to SAM surfaces with -PO4H2 and -COOH. The pre-deposited HA can rapidly induce biomimetic apatite layer formation after immersion in 1.5 SBF for 18 h regardless of the amount of pre-deposited HA. The results suggested that the pre-deposition of HA onto these functionalized SAM surfaces might be an effective and fast way to prepare biomimetic apatite coatings on surgical implants.     

TEM-EDX study of mechanism of bonelike apatite formation on bioactive titanium metal in simulated body fluid

Bioactive titanium metal, which forms a bonelike apatite layer on its surface in the body and bonds to the bone through the apatite layer, can be prepared by NaOH and heat treatments to form an amorphous sodium titanate layer on the metal. In the present study, the mechanism of apatite formation on the bioactive titanium metal has been investigated in vitro. The metal surface was examined using transmission electron microscopy and energy dispersive X-ray spectrometry as a function of the soaking time in a simulated body fluid (SBF) and complemented with atomic emission spectroscopy analysis of the fluid. It was found that, immediately after immersion in the SBF, the metal exchanged Na(+) ions from the surface sodium titanate with H(3)O(+) ions in the fluid to form Ti-OH groups on its surface. The Ti-OH groups, immediately after they were formed, incorporated the calcium ions in the fluid to form an amorphous calcium titanate. After a long soaking time, the amorphous calcium titanate incorporated the phosphate ions in the fluid to form an amorphous calcium phosphate with a low Ca/P atomic ratio of 1.40. The amorphous calcium phosphate thereafter converted into bonelike crystalline apatite with a Ca/P ratio of 1.65, which is equal to the value of bone mineral. The initial formation of the amorphous calcium titanate is proposed to be a consequence of the electrostatic interaction of negatively charged units of titania, which are dissociated from the Ti-OH groups, with the positively charged calcium ions in the fluid. The amorphous calcium titanate is speculated to gain a positive charge and to interact with the negatively charged phosphate ions in the fluid to form the amorphous calcium phosphate, which eventually stabilizes into bonelike crystalline apatite.