A preliminary study on osteoinduction of two kinds of calcium phosphate ceramics.

With respect to the effect of material factors on calcium phosphate biomaterial-induced osteogenesis, the osteoinductive property of two kinds of porous hydroxyapatite ceramics, which were made by different producers, was investigated in dorsal muscles of dogs. One hydroxyapatite ceramic (S-HA), macroporous implants with rough pore walls containing abundant micropores, was made by Sichuan Union University (Chengdu, China); the other hydroxyapatite ceramic (J-HA), porous implants with smooth macropore walls composed of regularly aligned crystal grains, was provided by Mitsubishi Ceramic Int. (Japan). Different tissue response was detected histologically and microradiographically after the ceramic samples had been implanted in dorsal muscles of dogs for 3 and 6 months. Bone formation was found in S-HA at 3 months, which increased at 6 months. In contrast, no bone formation was detected in J-HA at both 3 and 6 months. These results indicate that with the special architecture, calcium phosphate ceramic can induce bone formation in soft tissue. As both materials were very similar in their chemical and crystallographic structures, but varied in their microstructures, the latter seem to be an important factor affecting the osteoinductive capacity of calcium phosphate ceramics. These data suggest that, by controlling the preparation of calcium phosphate ceramic, bone substitutes with intrinsic osteoinductive property can be developed from calcium phosphates.     

Repairing segmental bone defects with living porous ceramic cylinders: an experimental study in dog femora.

Twenty-one porous hydroxyapatite-tricalcium phosphate ceramic cylinders 1.5 cm long and 1.2 cm in diameter were swathed with fresh autogenetic periostea taken from 21 dogs and implanted in the same animals' muscles to get living ceramic bone substitutes. These substitutes contained autogenetic growth stimulators including osteoblasts and other multipotential cells. One month later, they were transferred to the segmental bone defect sites created in femoral diaphysis of the same animals. The roentgenograms showed that in time the boundaries between the cylinders and bone sections became vague. X-ray diffraction analysis indicated that the spectra of the samples tended to be similar to those of natural bones by 6 months postoperatively. Their bending strengths also increased gradually. After the cylinders were transferred from muscles to the bone defect sites, newly formed bone tissues rapidly increased and the cylinders gradually fused with the contacted bones 2 months later. By 4 and 6 months, bone tissue occupied most areas of the materials. The ratio of newly formed bone tissue had a large lead over the materials. Haversian systems were clearly observed and matured bone tissues filled the ceramic pores and connected with each other. Results suggested that culturing complexes that consist of autogenetic periostea and biomaterials, taking advantage of living organic culturing medium, should be an effective approach to get satisfactory bioactive bone substitutes. It also provides a basis for clinically repairing bone defects in bearing sites with complex bioceramics.     

Material-dependent bone induction by calcium phosphate ceramics: a 2.5-year study in dog

Bone induction by different calcium phosphate biomaterials has been reported previously. With regard to (1) whether the induced bone would disappear with time due to the absence of mechanical stresses and (2) whether this heterotopically formed bone would give rise to uncontrolled growth, a long-time investigation of porous hydroxyapatite ceramic (HA), porous biphasic calcium phosphate ceramic (TCP/HA, BCP), porous alpha-tricalcium phosphate ceramic (alpha-TCP) and porous beta-tricalcium phosphate ceramic (beta-TCP) was performed in dorsal muscles of dog, for 2.5 years. Histological observation, backscattered scanning electron microscopy observation and histomorphometric analysis were made on thin un-decalcified sections of retrieved samples. Normal compact bone with bone marrow was found in all HA implants (n = 4) and in all BCP implants (n = 4), 48 +/- 4% pore area was filled with bone in HA implants and 41 +/- 2% in BCP implants. Bone-like tissue, which was a mineralised bone matrix with osteocytes but lacked osteoblasts and bone marrow, was found in all beta-TCP implants (n = 4) and in one of the four alpha-TCP implants. Both normal bone and bone-like tissues were confined inside the pores of the implants. The results show that calcium phosphate ceramics are osteoinductive in muscles of dogs. Although the quality and quantity varied among different ceramics, the induced bone in both HA and BCP ceramics did neither disappear nor grow uncontrollably during the period as long as 2.5 years.     

Osteoinduction of hydroxyapatite/β-tricalcium phosphate bioceramics in mice with a fractured fibula

Many studies have shown that calcium phosphate ceramics can induce bone formation in non-osseous sites without the application of any osteoinductive biomolecules, but the mechanisms of this phenomenon (intrinsic osteoinduction of bioceramics) remain unclear. In this study, we compared the intrinsic osteoinduction of porous hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) implanted in mice at different sites. In 30 mice the left fibula was fractured and the right fibula was kept intact. A porous HA/β-TCP cylinder was implanted into both the left (group 1) and right (group 2) leg muscles of each animal. In addition, two HA/β-TCP cylinders were bilaterally implanted into leg subcutaneous pockets (group 3) in each of the remaining 15 mice. New bone formation was studied in the three groups by histology, histomorphometry and immunostaining. In group 1 new bone was observed at week 6 and bone marrow appeared at week 12. In group 2 new bone was observed at week 8 and bone marrow appeared at week 12. The new bone area percentage in group 1 was significantly higher than in group 2 at both weeks 8 and 12. In contrast, group 3 did not show any new bone within the period studied. These differences were explained based on the location of the implants and thus their proximity to the osteogenic environment of fracture healing. The results support the hypothesis that intrinsic osteoinduction by calcium phosphate ceramics is the result of adsorption of osteoinductive substances on the surface.     

管状和柱状磷酸三钙陶瓷人工骨修复长骨大段骨缺损的对比研究

为研制理想的、能较快修复长骨大段骨缺损的陶瓷人工骨 ,我们将管状磷酸三钙 ( TTCP)和柱状磷酸三钙 ( CTCP)陶瓷人工骨分别植入兔桡骨于 1cm缺损处。术后 4、12周时取材 ,作大体组织形态学、新骨形成定量观察及抗折强度测试。术后 4、12周时 TTCP内新骨形成量明显多于 CTCP,术后 12周时 ,植入材料与宿主骨结合紧密 ,TTCP的降解速度快于 CTCP,抗折强度前者明显高于后者 ( P<0 .0 1)。研究结果表明 ,TTCP比 CTCP设计更合理 ,能更快促进长骨大段骨缺损的修复 ,是一种较理想的人工骨材料     

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。     

Resorption of apatite-wollastonite containing glass-ceramic and beta-tricalcium phosphate in vivo

Apatite-wollastonite containing glass ceramic is considered to be difficult to resorb, but we experienced the disappearance of the porous type of Apatite-wollastonite glass ceramic particles . In this study, the resorption of porous apatite-wollastonite glass-ceramic implanted in the femurs of rabbits was investigated, and the process was compared with beta-tricalcium phosphate, a resorbable ceramics. Porous apatite-wollastonite glass-ceramic (70, 80, and 90% porosity) and beta-tricalcium phosphate (75% porosity) were implanted in the femurs of Japanese white rabbits. Samples were harvested and examined 0, 4, 8, 12, 24 and 36 weeks after implantation. Quantitative analysis of the radiographic and histologic findings was performed with NIH Image software. Radiographic examination demonstrated that the radiopacity and size of the porous apatite-wollastonite glassceramic cylinders decreased gradually after implantation. Histologic examination revealed that the surface area of the apatite-wollastonite glass-ceramic cylinders decreased continuously, and approached 20% of the original area 36 weeks after implantation. However, the resorption rate of porous apatite-wollastonite glass-ceramic was slower than that of beta-tricalcium phosphate. Toluidine blue staining showed abundant new bone formation on the surface of the apatite-wollastonite glassceramic matrix. Considering its mechanical strength, gradual resorption characteristics, and good osteochonductive activity, porous apatite-wollastonite glass-ceramic appears to be a suitable artificial bone substitutes.     

Replacement of segmental bone defects using porous bioceramic cylinders: a biomechanical and X-ray diffraction study

A porous ceramic material [hydroxyapatitetricalcium phosphate (HA-TCP)] was implanted in the femora of 30 dogs to investigate the possibility of using this material to repair segmental bone defects. A bone segment, 1.5 cm in length, was removed from the diaphysis of one femur in each dog to create the defect. Cylinders of corresponding size were inserted into the defects. The animals were divided into three groups with recovery times of 2 months, 4 months, and 6 months, respectively. The implants were harvested and subjected to biomechanic tests (bending strength) and X-ray diffraction analysis. The bending strengths of the implant construct increased gradually over time postoperatively. The values of strength for the three different time groups had significant variations (p < 0.05). The X-ray diffraction analysis indicated that the peaks of the TCP included in the cylinders decreased in intensity after implantation and tended to be similar to those of natural bone by 6 months after operation. Conversely, the peaks for the HA had fewer changes compared with preimplantation values. Based on the results of this experiment it was concluded that the porous HA-TCP ceramic cylinders have potential for repair of segmental bone defects if assisted by adequate stabilizing fixtures during the early postoperative period.     

The fabrication and biochemical evaluation of alumina reinforced calcium phosphate porous implants

Alumina reinforced calcium phosphate porous implants were manufactured to improve the mechanical strength while maintaining the bioactivity of calcium phosphate ceramics. The alumina porous bodies, which provided the mechanical strength, were fabricated by a polyurethane sponge method and multiple coating techniques resulted in the porous bodies with a 90-75% porosity and a compressive strength of up to approximately 6MPa. The coating of hydroxyapatite (HAp) or tricalcium phosphate (beta-TCP) was performed by dipping the alumina porous bodies into calcium phosphate ceramic slurries and sintering the specimens. The fairly strong bonding between the HAp or TCP coating layer and the alumina substrate was obtained by repeating the coating and sintering processes. The biochemical evaluations of the porous implants were conducted by in vitro and in vivo tests. For in vitro test, the implants were immersed in Ringer's solution and the release of Ca and P ions were detected and compared with those of calcium phosphate powders. For in vivo test, the porous bodies were implanted into mixed breed dogs and bone mineral density measurements and histological studies were conducted. The alumina reinforced HAp porous implants had a higher strength than the HAp porous implants and exhibited a similar bioactivity and osteoconduction property to the HAp porous implants.     

骨诱导性磷酸钙陶瓷材料修复牙槽突裂

BACKGROUND: In our previous studies, we had prepared calcium phosphate ceramics with better ectopic osteogenesis. OBJECTIVE: To explore the effect of novel osteoinductive calcium phosphate ceramics in the repairing of alveolar cleft. METHODS: Bilaterl alveolar defects were created in nine immature beagles. Three months later, osteoinductive calcium phosphate ceramics with high modular surface (experimental group) and smooth surface (control group) were randomly implanted in each side of the defect. Meanwhile, the corresponding material was implanted into the thigh muscle. New bone formation in the implanted region, osteogenesis in the implanted region and muscle, and respair results were respectively observed by fluorescence microscope, light microscope and CT at 4, 8 and 12 weeks after implantation. RESULTS AND CONCLUSION: (1) Fluorescence microscope observation: A circular permutation of red, yellow and green fluorescent strip could be observed in both two groups. (2) Light microscope observation: At 12 weeks after implantation, in the experimental group, the bone reconstruction was obvious, the implant material was decomposed gradually, the gap was filled with a large number of mature bone that combined with the rest material closely, and numerous Haversian canals appeared; the control group was similar but slightly inferior to the experimental group in the quality of new bone. The experimental group material successfully induced heterotopic osteogenesis in muscle, while the control did not. (3) CT examination: The two group materials restored the appearance and continuity of the alveolar ridge, and made no effect on the eruption of permanent teeth in both sides of the defect. To conclude, our findings suggest that the novel osteoinductive calcium phosphate ceramic exhibits advantages in alveolar cleft repair with earlier osteogenesis activation, faster osteogenesis rate and more bone formation than those traditional materials.     

Osseointegration of composite calcium phosphate bioceramics

The resistance of macroporous calcium phosphate ceramics to compressive strength generally is low and depends on, among other factors, porosity percentage and pore size. A compromise always is adopted between high porosity, required for a good integration, and mechanical strength, which increases with material density. We improved the strength of macroporous calcium phosphate ceramics of interconnected porosity by filling the pores with a highly soluble, self-setting calcium phosphate cement made of TCP and DCPD. Cylinders of the resulting material were implanted in sheep condyles and subjected to histological analysis after 20, 60, and 120 days. Microradiographs were made of the histological sections. The control material consisted of ceramic that had not been loaded with cement. Progressive ingrowth of bone into the ceramic pores occurred as the cement was degraded during the first implantation period. Marked degradation of the cement was apparent after 2 months, with fragmentation of the cement in most of the pores and the presence of bone tissue between the fragments. All the cement had been replaced by bone after 4 months. Some fragments of cement still were embedded in the newly formed bone. There was no significant difference between the integration of loaded and nonloaded ceramics. Filling the macroporous ceramic pores with a calcium phosphate cement significantly improved the mechanical strength of these ceramics without modifying their integration in the healing bone.     

晶须化磷酸钙多孔生物活性陶瓷修复犬股骨髁缺损

BACKGROUND: Previous studies have demonstrated that the internal microstructure of porous calcium phosphate ceramics after the whiskering process has some changes, and obtain good mechanical properties. OBJECTIVE: To further investigate the effect of whisker-covered porous calcium phosphate ceramics in repair of canine femoral condyle defects. METHODS: Highly interconnected porous calcium phosphate ceramics was prepared by placeholder method. The whiskering of the materials was finished by hydrothermal process. Fifteen healthy adult beagle dogs were selected in this study. A 10 mm×10 mm cylindrical inclusive bone defect was made bilaterally on the lateral femoral condyle with a drill. The porous calcium phosphate ceramics after the whiskering process was implanted onto the right femoral condyle as experiment group. The porous calcium phosphate ceramics without the whiskering process was implanted onto the left femoral condyle as control group. At 2, 4, 8, and 12 weeks after implantation, X-ray and dual-energy X-ray test were conducted in the bone defect area respectively. RESULTS AND CONCLUSION: (1) X-ray: With the increase of time, the interface between bone defect and normal bone of two groups gradually blurred, disappeared, and completely fused at 12 weeks. The material in the control group was partially dissolved, while there was no obvious dissolution in the experiment group. No significant difference in the X-ray scores was found between two groups at different time points. (2) Dual-energy X-ray: With the increase of time, the bone mineral density of the two groups both increased gradually, but there was no significant difference in the bone mineral density at different time points between these two groups. These results demonstrate that the porous calcium phosphate ceramics after the whiskering process has good ability to repair the defects of femoral condyle.       

Histomorphological researches on large porous hydroxyapatite cylinder tubes with polylactic acid surface coating in different nonskeletal sites in vivo

Porous hydroxyapatite (HA) ceramic cylinder tubes coated with polylactic acid on the exposed surfaces were implanted in four nonskeletal sites (omentum, peritoneum, vastus lateralis, and side of femur). Six months postoperatively, proper amount of Chinese ink was injected to dye the implanting areas. Decalcified and nondecalcified sections were observed under inverted microscope. The results showed that the soft tissues around the HA cylinder tubes in peritoneum, vastus lateralis, and side of femur groups appeared visible black. Some small blacked vascular architectures were also discernible. However in omentum group, only small number of blacked vessels existed. Histological observations indicated that vascularization and ossification occurred in peritoneum, vastus lateralis, and side of femur groups. In omentum group, there was no any sign of vascularization and ossification. A conclusion could be made in this study that excepting bones and muscles, parietal peritoneum could serve as a potential spot for culturing histoengineering hydroxyapatite (HA)-polylactic acid (PLA) ceramic bone substitutes.     

Porosity-graded hydroxyapatite ceramics to replace natural bone

Porous hydroxyapatite HA bodies were prepared with an aim to simulate bone tissue morphology. By varying the characteristics of starting HA powders and the impregnation strategy of cellulosic sponges with rheologically optimized slurries, a wide range of physico-chemical and mechanical properties of the porous ceramics can be obtained. The samples were characterized microstructurally, by density and porosimetry and by mechanical strength. Cylindrical specimens exhibiting a porosity gradient showed a promising behaviour after implantation in rabbits' femur: newly formed bone grew in tight contact with the ceramic in a very short time, no modified cells are induced and bone tissue fills even the inner pores.     

3D microenvironment as essential element for osteoinduction by biomaterials

In order to unravel the mechanism of osteoinduction by biomaterials, in this study we investigated the influence of the specific surface area on osteoinductive properties of two types of calcium phosphate ceramics. Different surface areas of the ceramics were obtained by varying their sintering temperatures. Hydroxyapatite (HA) ceramic was sintered at 1150 and 1250 degrees C. Biphasic calcium phosphate (BCP) ceramic, consisting of HA and beta-tricalcium phosphate (beta-TCP), was sintered at 1100, 1150 and 1200 degrees C. Changes in sintering temperature did not influence the chemistry of the ceramics; HA remained pure after sintering at different temperatures and the weight ratio of HA and beta-TCP in the BCP was independent of the temperature as well. Similarly, macroporosity of the ceramics was unaffected by the changes of the sintering temperature. However, microporosity (pore diameter <10 microm) significantly decreased with increasing sintering temperature. In addition to the decrease of the microporosity, the crystal size increased with increasing sintering temperature. These two effects resulted in a significant decrease of the specific surface area of the ceramics with increasing sintering temperatures. Samples of HA1150, HA1250, BCP1100, BCP1150 and BCP1200 were implanted in the back muscles of Dutch milk goats and harvested at 6 and 12 weeks post implantation. After explantation, histomorphometrical analysis was performed on all implants. All implanted materials except HA1250 induced bone. However, large variations in the amounts of induced bone were observed between different materials and between individual animals. Histomorphometrical results showed that the presence of micropores within macropore walls is necessary to make a material osteoinductive. We postulate that introduction of microporosity within macropores, and consequent increase of the specific surface area, affects the interface dynamics of the ceramic in such a way that relevant cells are triggered to differentiate into the osteogenic lineage.     

Comparative study of biphasic calcium phosphate ceramics impregnated with rhBMP-2 as bone substitutes

We investigated pellet-shaped implants prepared from biphasic calcium phosphate (BCP) ceramics with five different ratios of hydroxyapatite (HAP) to beta-tricalcium phosphate (beta-TCP) to evaluate these ceramics as bone substitutes. BCP ceramics impregnated with different doses of recombinant human bone morphogenetic protein 2 (rhBMP-2) (1, 5, and 10 microg) were used for experimental purposes and ceramics without rhBMP-2 were used for control. The pellets were implanted under the pericranium in adult Wistar male rats and were harvested 8 weeks after implantation. The retrieved pellets were then examined radiologically, histologically, and histomorphometrically. The results revealed that the pellets treated with rhBMP-2 exhibited new bone and bone marrow, whereas control pellets produced fibrous connective tissues. The formation of new bone induced by rhBMP-2 was dose dependent. The extent of bone and bone marrow formation and the degree of resorption of the ceramic particles were significantly higher in the pellets composed of 25% HAP-75% TCP. In this study, bioresorption of the ceramic produced favorable conditions for rhBMP-2-induced bone formation.     

镍钛形态记忆合金与骨组织相容性的形态学

目的：观察镍钛形态记忆合金植入动物骨组织后局部组织的反应、骨缺损的修复情况，研究镍钛合金与骨的组织相容性，为镍钛合金作为生物医学材料在临床上广泛应用提供理论依据。方法：纯系日本白性兔，实验组在股骨下1／3处植入镍钛合金。于术后4、8、16w，在植入区上下0．5cm处横断取材。将骨块置于4％多聚甲醛-2．5％戊二醛混合液内固定。制作半薄切片，经1％甲苯胺蓝染色，光镜观察；制作超薄切片，透射电镜观察。结果：实验组表现出与对照组相似的骨缺损修复过程。结论：此镍钛形态记忆合金与骨组织具有良好的相容性。     

Engineering of bone using bone marrow stromal cells and a silicon-stabilized tricalcium phosphate bioceramic: evidence for a coupling between bone formation and scaffold resorption

Resorbable porous ceramic constructs, based on silicon-stabilized tricalcium phosphate, were implanted in critical-size defects of sheep tibias, either alone or after seeding with bone marrow stromal cells (BMSC). Only BMSC-loaded ceramics displayed a progressive scaffold resorption, coincident with new bone deposition. To investigate the coupled mechanisms of bone formation and scaffold resorption, X-ray computed microtomography (muCT) with synchrotron radiation was performed on BMSC-seeded ceramic cubes. These were analyzed before and after implantation in immunodeficient mice for 2 or 6 months. With increasing implantation time, scaffold thickness significantly decreased while bone thickness increased. The muCT data evidenced that all scaffolds showed a uniform density distribution before implantation. Areas of different segregated densities were instead observed, in the same scaffolds, once seeded with cells and implanted in vivo. A detailed muX-ray diffraction analysis revealed that only in the contact areas between deposited bone and scaffold, the TCP component of the biomaterial decreased much faster than the HA component. This event did not occur at areas away from the bone surface, highlighting coupling and cell-dependency of the resorption and matrix deposition mechanisms. Moreover, in scaffolds implanted without cells, both the ceramic density and the TCP:HA ratio remained unchanged with respect to the pre-implantation analysis.     

组织工程骨-假体界面微观结构与元素分析的意义

目的研究假体-组织工程骨界面的微观结构和钙磷元素及构成比动态变化及意义。方法取新西兰大白兔15只,将兔骨髓间充质干细胞培养、扩增及诱导后,与珊瑚羟基磷灰石复合构建组织工程骨;双侧股骨髁分别制作一0.5cm×1.2cm骨缺损,骨缺损中央植入0.2cmx1.0cm钛合金植入体,左侧植入体周围植入组织工程骨,右侧仅植入珊瑚羟基磷灰石为对照,于术后4周、8周和l2周分别行X线检查、扫描电镜及能谱分析观察植入体表面微观结构和钙磷元素百分含量及比值的变化。结果 X线检查示,实验组术后8-12周可见大量模糊的高密度骨痂影,缺损区与周围骨质间分界变模糊。对照组各时间点无明显变化;扫描电镜示,实验组术后8、12周植入体表面孔隙内有大量无定形物质,而对照组未见有无定形物质。能谱分析示,不同时间点实验组较对照组内钙、磷元素百分含量高,有显著性差异（〈0.05）,随着时间的变化实验组和对照组Ca、P百分含量都呈增高的趋势,但12周和8周相比无显著性差异（〉0.05）。实验组内钙磷比值随时间变化有逐渐增大趋势,8周时达峰值,8周后缓慢下降。结论假体-组织工程骨界面钙、磷元素及构成比的动态变化表明骨整合的形成,并随着时间的延长骨改建逐步增加。     

Biological performance of uncoated and octacalcium phosphate-coated Ti6Al4V

The in vivo behavior of a porous Ti6Al4V material that was produced by a positive replica technique, with and without an octacalcium phosphate (OCP) coating, has been studied both in the back muscle and femur of goats. Macro- and microporous biphasic calcium phosphate (BCP) ceramic, known to be both osteoconductive and able to induce ectopic bone formation, was used for comparison purpose. The three groups of materials (Ti6Al4V, OCP Ti6Al4V and BCP) were implanted transcortically and intramuscularly for 6 and 12 weeks in 10 adult Dutch milk goats in order to study their osteointegration and osteoinductive potential. In femoral defects, both OCP Ti6Al4V and BCP were performing better than the uncoated Ti6Al4V, at both time points. BCP showed a higher bone amount than OCP Ti6Al4V after 6 weeks of implantation, while after 12 weeks, this difference was no longer significant. Ectopic bone formation was found in both OCP Ti6Al4V and BCP implants after 6 and 12 weeks. The quantity of ectopically formed bone was limited as was the amount of animals in which the bone was observed. Ectopic bone formation was not found in uncoated titanium alloy implants, suggesting that the presence of calcium phosphate (CaP) is important for bone induction. This study showed that CaPs in the form of coating on metal implants or in the form of bulk ceramic have a significantly positive effect on the bone healing process.