In vivo behavior of a novel injectable calcium phosphate cement compared with two other commercially available calcium phosphate cements

The aim of this study was to investigate the physicochemical and biological properties of a newly developed calcium phosphate cement (CPC). The novel cement was compared with two other commercially available CPCs. After mixing the powder and liquid phase, the CPCs were injected as a paste into a rabbit distal femoral defect model. The CPCs were evaluated after 24 h, 6 weeks, 26 weeks, and 52 weeks. The novel CPC was easy to handle and was fast setting. X-ray diffraction (XRD) and Fourier Transform Infrared Spectrometry (FTIR) at the different implantation periods showed that the cement had converted to carbonated hydroxyapatite and remained stable over time. Histological evaluation showed bone apposition on the cement surface without any inflammatory response or fibrous encapsulation. At later time points, all CPCs were completely covered by a thin layer of bone. Osteoclast-like cells present at the interface resorbed parts of the cement mass. Histological and histomorphometrical analyses did not show any significant differences between the three implanted CPCs. The results indicate that the investigated CPC is biocompatible, osteoconductive, as well as osteotransductive and seems to be both biologically safe and effective as a bone void filler.     

Soft-tissue response to injectable calcium phosphate cements

In this study, the soft tissue reaction to two newly developed injectable calcium phosphate bone cements (cement D and W) was evaluated after implantation in the back of goats. For one of the cements (cement D) the tissue reaction was also investigated after varying the concentration of accelerator Na(2)HPO(4) in the cement liquid (resulting in cement D1 and D2). Eight healthy mature female Saanen goats were used. The cement was applied 10min after mixing while it was still moldable and plastic. The material was given a standardized cylindrical shape. Thirty-two implants of each cement formulation were inserted and left in place for 1, 2, 4, and 8weeks. At the end of the study, eight specimens of each material and healing period were available for further analysis. Two specimens were used for X-ray diffraction (XRD) and Fourier Transform Infrared Spectroscopy (FTIR) and six specimens were used for light microscopical evaluation. XRD and FTIR showed that the cements did set as microcrystalline carbonate apatite with the disappearance of monetite from the cements during implantation. Histological analysis showed that after 8weeks of implantation around all materials a thin soft-tissue capsule was formed (thickness ranging from 5 to 15 cell layers) with almost complete absence of inflammatory cells. Only in some specimens a slightly higher inflammatory reaction was observed. This was due to cement surface defects and a zone of dispersed particles near the cement-soft tissue interface. There was almost no resorption of the material after 8 weeks of implantation. In a few 4 and 8weeks samples, small areas of calcification were found in the fibrous capsule surrounding the implants. On the basis of our observations, we conclude that the tested cements were biocompatible and can be used next to soft tissue.     

In vitro growth factor release from injectable calcium phosphate cements containing gelatin microspheres

To improve the in vivo resorption of an injectable calcium phosphate cement (CPC) for bone tissue engineering purposes, in previous experiments macroporosity was introduced by the in situ degradation of incorporated gelatin microspheres. Gelatin microspheres are also suitable carriers for osteoinductive drugs/growth factors, where release occurs concomitantly with degradation of the hydrogel. Introduction of these microspheres into CPC can alter the release pattern of the cement, which usually shows a marginal release of incorporated drugs. The goal of this study was to determine the in vitro release characteristics of gelatin microsphere CPC. For this, recombinant human TGF-beta1, bFGF, and BMP-2 were labeled with (125)I and loaded onto gelatin type A (porcine, pI = 7.0-9.0)/type B (bovine, pI = 4.5-5.0) microspheres for a short (instant) and longer (prolonged) time before mixing them with the cement. Radioactivity of the resulting 5 or 10 wt % gelatin microsphere CPC composites was monitored for 6 weeks when subjected to proteolytic medium. Drug-loaded CPC was used as control. Results showed that release pattern/efficiency of gelatin microsphere CPCs and CPC controls was highly dependent on the type of growth factor but unaffected by the amount of growth factor. With gelatin microsphere CPC, release was also dependent on the type of gelatin, total volume of incorporated microspheres, and loading method.     

In vivo behavior of calcium phosphate scaffolds with four different pore sizes

The goal of the present study was to assess the effect of macropore size on the in vivo behavior of ceramic scaffolds. For that purpose, beta-tricalcium phosphate (beta-TCP) cylinders with four different macropore sizes (150, 260, 510, and 1220 microm) were implanted into drill hole defects in cancellous bone of sheep and their resorption behavior was followed for 6, 12 and 24 weeks. The scaffolds were evaluated for biocompatibility, and new bone formation was observed macroscopically, histologically and histomorphometrically. Histomorphometrical measurements were performed for the whole defect area and for the area subdivided into three concentric rings (outer, medial, and inner ring). All implants were tolerated very well as evidenced by the low amount of inflammatory cells and the absence of macroscopic signs of inflammation. Resorption proceeded fast since less than 5% ceramic remained at 24-week implantation. Hardly any effect of macropore size was observed on the in vivo response. Samples with an intermediate macropore size (510 microm) were resorbed significantly faster than samples with smaller macropore sizes (150 and 260 microm). However, this fast resorption was associated with a lower bone content and a higher soft tissue content. At 12 and 24 weeks, the latter differences had disappeared. Bone was more abundant in the outer ring than in the rest of the blocks at 6 weeks, and in the outer and medial ring compared to the inner ring at 12 weeks.     

In vitro biodegradation of three brushite calcium phosphate cements by a macrophage cell-line

Depending upon local conditions, brushite (CaHPO4 x 2 H2O) cements may be largely resorbed or (following hydrolysis to hydroxyapatite) remain stable in vivo. To determine which factors influence cement resorption, previous studies have investigated the solution-driven degradation of brushite cements in vitro in the absence of any cells. However, the mechanism of cell-mediated biodegradation of the brushite cement is still unknown. The aim of the current study was to observe the cell-mediated biodegradation of brushite cement formulations in vitro. The cements were aged in the presence of a murine cell line (RAW264.7), which had the potential to form osteoclasts in the presence of the receptor for nuclear factor kappa B ligand (RANKL) in vitro, independently of macrophage colony stimulating factor (M-CSF). The cytotoxicity of the cements on RAW264.7 cells and the calcium and phosphate released from materials to the culture media were analysed. Scanning electron microscopy (SEM) and focused ion beam (FIB) microscopy were used to characterise the ultrastructure of the cells. The results showed that the RAW264.7 cell line formed multinucleated TRAP positive osteoclast-like cells, capable of ruffled border formation and lacunar resorption on the brushite calcium phosphate cement in vitro. In the osteoclast-like cell cultures, ultrastructural analysis by SEM revealed phenotypic characteristics of osteoclasts including formation of a sealing zone and ruffled border. Penetration of the surface of the cement, was demonstrated using FIB, and this showed the potential demineralising effect of the cells on the cements. This study has set up a useful model to investigate the cell-mediated cement degradation in vitro.     

Of the in vivo behavior of calcium phosphate cements and glasses as bone substitutes

The use of injectable self-setting calcium phosphate cements or soluble glass granules represent two different strategies for bone regeneration, each with distinct advantages and potential applications. This study compares the in vivo behavior of two calcium phosphate cements and two phosphate glasses with different composition, microstructure and solubility, using autologous bone as a control, in a rabbit model. The implanted materials were alpha-tricalcium phosphate cement (cement H), calcium sodium potassium phosphate cement (cement R), and two phosphate glasses in the P(2)O(5)-CaO-Na(2)O and P(2)O(5)-CaO-Na(2)O-TiO(2) systems. The four materials were osteoconductive, biocompatible and biodegradable. Radiological and histological studies demonstrated correct osteointegration and substitution of the implants by new bone. The reactivity of the different materials, which depends on their solubility, porosity and specific surface area, affected the resorption rate and bone formation mainly during the early stages of implantation, although this effect was weak. Thus, at 4 weeks the degradation was slightly higher in cements than in glasses, especially for cement R. However, after 12 weeks of implantation all materials showed a similar degradation degree and promoted bone neoformation equivalent to that of the control group.     

Tantalumpentoxide as a radiopacifier in injectable calcium phosphate cements for bone substitution

The chemical resemblance of calcium phosphate (CaP) cements and the mineral phase of bone is a problem in distinguishing CaP cement from bone tissue by means of common, noninvasive techniques (e.g., X-ray imaging and microcomputed tomography [μCT]). In this study, the feasibility of using tantalumpentoxide (Ta(2)O(5)) powder as radiopacifier in CaP cements was analyzed. A distal femoral condyle model in male adult Wistar rats was used. After 6 weeks of implantation time, the results were analyzed by means of μCT and histology. Unambiguous distinction of CaP cement from native bone tissue and volumetric measurements of the materials appeared to be possible by means of μCT scanning. Furthermore, there was no evidence of either inflammation or fibrous tissue around the implant materials or at the bone-material interface. In conclusion, the addition of Ta(2)O(5) as a radiopacifying additive to CaP cements allows discrimination between bone substitute and surrounding bone tissue. Consequently, Ta(2)O(5) represents an effective and biocompatible additive in CaP cements for in vivo monitoring purposes.     

Bone response to fast-degrading, injectable calcium phosphate cements containing PLGA microparticles

Apatitic calcium phosphate cements (CPC) are frequently used to fill bone defects due to their favourable clinical handling and excellent bone response, but their lack of degradability inhibits complete bone regeneration. In order to render these injectable CaP cements biodegradable, hollow microspheres made of poly (D,L-lactic-co-glycolic) acid (PLGA) have been previously used as porogen since these microspheres were shown to be able to induce macroporosity upon degradation as well as to accelerate CPC degradation by release of acid degradation products. Recently, the capacity of PLGA microspheres to form porosity in situ in injectable CPCs was optimized by investigating the influence of PLGA characteristics such as microsphere morphology (dense vs. hollow) and end-group functionalization (acid terminated vs. end-capped) on acid production and corresponding porosity formation in vitro. The current study has investigated the in vivo bone response to CPCs containing two types of microspheres (hollow and dense) made of PLGA with two different end-group functionalizations (end capped and acid terminated). Microspheres were embedded in CPC and injected in the distal femoral condyle of New Zealand White Rabbits for 6 and 12 weeks. Histological results confirmed the excellent biocompatibility and osteoconductivity of all tested materials. Composites containing acid terminated PLGA microspheres displayed considerable porosity and concomitant bone ingrowth after 6 weeks, whereas end capped microspheres only revealed open porosity after 12 weeks of implantation. In addition, it was found that dense PLGA microspheres induced significantly more CPC degradation and bone tissue formation compared to hollow PLGA microspheres. In conclusion, it was shown that PLGA microspheres have a strong capacity to induce fast degradation of injectable CPC and concomitant replacement by bone tissue by controlled release of acid polymeric degradation products without compromising the excellent biocompatibility and osteoconductivity of the CPC matrix.     

一种可注射体内成孔的磷酸钙骨水泥

背景：磷酸钙骨水泥存在脆性大、抗水溶性(血溶性)差、力学性能不足、降解缓慢等缺点,其临床应用受到一定限制,故需要对其进行改性研究。 目的：制备一种具有一定强度、孔隙率、适合骨生长的多孔磷酸钙骨水泥生物支架材料。 方法：以磷酸钙骨水泥为基本体系,液相采用壳聚糖的弱酸溶液,以提高磷酸钙骨水泥的可塑性和黏弹性,使骨水泥具有可注射性,显著提升骨水泥的应用范围及应用舒适度。固相为双相磷酸钙(磷酸四钙+磷酸氢钙)粉体,并在固相中添加一定量的甘露醇及聚乳酸-乙醇酸共聚物作为造孔剂,制备磷酸钙支架材料。 结果与结论：此材料孔径可达到10~300 μm。添加60%致孔剂时,磷酸钙骨水泥固化体孔隙率可达到(68.3±1.5)%。磷酸钙骨水泥孔隙率的增加使材料的力学性能下降,其抗压强度从最初不含致孔剂时的(53.0±1.4) MPa下降到含60%致孔剂的(2.5±0.2) MPa。实验制备的此种多孔磷酸钙骨水泥材料,是具有一定抗压强度、较好的孔隙率,并能体内降解的可注射生物支架材料。     

Conversion of octacalcium phosphate in calcium phosphate cements

This study investigated the in vitro conversion reaction in calcium phosphate cements (CPCs) containing octacalcium phosphate (OCP) as one of the reagents. OCP is known to be a precursor for apatite formation in vivo. The reaction products were characterized using infrared spectroscopy and X-ray diffraction. Although the conversion of OCP into hydroxyapatite is thermodynamically favorable, OCP only yields apatite formation in CPC provided it is combined with a highly soluble Ca(2+) and OH(-) releasing reaction partner. In this respect, tetracalcium phosphate is a promising compound. Adding small amounts of monocalcium phosphate monohydrate can stimulate the setting through intermediate brushite formation. The preparation method of OCP might drastically affect the performance of the cement. The reaction path of the setting of these CPC probably does not conform to the singular point principle described in the literature, and an in situ hydrolysis of OCP to apatite is conceivable. Simulation of apatite formation using OCP as the precursor and/or seed in CPC might be beneficial for some biomedical applications.     

Processing and in vivo evaluation of multiphasic calcium phosphate cements with dual tricalcium phosphate phases

Calcium phosphate cements (CPCs) use the simultaneous presence of several calcium phosphates phases. This is done to generate specific bulk and in vivo properties. This work has processed and evaluated novel multiphasic CPCs containing dual tricalcium phosphate (TCPs) phases. Dual TCPs containing α- and β-TCP phases were obtained by thermal treatment. Standard CPC (S-CPC) was composed of α-TCP, anhydrous dicalcium phosphate and precipitated hydroxyapatite, while modified CPC (DT-CPC) included both α- and β-TCP. Physicochemical characterization of these CPCs was based on scanning electron microscopy, X-ray diffraction, specific surface area (SSA) and particle size (PS) analysis and mechanical properties. This characterization allowed the selection of one DT-CPC for setting time, cohesion and biological assessment compared with S-CPC. Biological assessment was carried out using a tibial intramedullary cavity model and subcutaneous pouches in guinea pigs. Differences in the surface morphology and crystalline phases of the treated TCPs were detected, although PS analysis of the milled CPC powders produced similar results. SSA analysis was significantly higher for DT-CPC with α-TCP treated at 1100°C for 5h. Poorer mechanical properties were found for DT-CPC with α-TCP treated at 1000°C. Setting time and cohesion, as well as the in vivo performance, were similar in the selected DT-CPC and the S-CPC. Both CPCs created the desired host reactions in vivo.     

Reaction of calcium phosphate cements with different amounts of tetracalcium phosphate and dicalcium phosphate anhydrous.

Calcium phosphate cements (CPCs) with different amounts of tetracalcium phosphate (TTCP) and dicalcium phosphate anhydrous (DCPA) (TTCP/DCPA molar ratio from 0.25 to 2.00) were prepared to further understand the setting reaction and the factors that could influence the properties of CPCs. Quantitative X-ray diffraction patterns, Fourier transform IR spectra, and diametral tensile strength of the set mass were measured along with pH measurements of the CPC suspension. Calcium-deficient hydroxyapatite (d-HAP) with a calcium to phosphate molar ratio of approximately 1.5 was formed initially in the CPC setting consisting of an equimolar mixture of TTCP and DCPA. This gradually transformed into stoichiometric HA (s-HA) with increasing incubation time. The s-HA was formed in the initial stage when the CPC contained an excess amount of TTCP. In contrast, maturation to s-HAP was slow when the CPC contained excess amounts of DCPA. The highest mechanical strength of set CPC was associated with an equimolar mixture of TTCP and DCPA, and the mechanical strength decreased as the TTCP/DCPA molar ratio deviated from 1.00. We concluded, therefore, that the setting reaction and the nature of the resulting set mass are dependent on the molar ratios of TTCP and DCPA.     

Effect of calcium carbonate on hardening, physicochemical properties, and in vitro degradation of injectable calcium phosphate cements

The main disadvantage of apatitic calcium phosphate cements (CPCs) is their slow degradation rate, which limits complete bone regeneration. Carbonate (CO?2?) is the common constituent of bone and it can be used to improve the degradability of the apatitic calcium phosphate ceramics. This study aimed to examine the effect of calcite (CaCO?) incorporation into CPCs. To this end, the CaCO? amount (0-4-8-12 wt %) and its particle size (12.0-μm-coarse or 2.5-μm-fine) were systematically investigated. In comparison to calcite-free CPC, the setting time of the bone substitute was delayed with increasing CaCO? incorporation. Reduction of the CaCO? particle size in the initial powder increased the injectability time of the paste. During hardening of the cements, the increase in calcium release was inversely proportional to the extent of CO?2? incorporation into apatites. The morphology of the carbonate-free product consisted of large needle-like crystals, whereas small plate-like crystals were observed for carbonated apatites. Compressive strength decreased with increasing CaCO? content. In vitro accelerated degradation tests demonstrated that calcium release and dissolution rate from the set cements increased with increasing the incorporation of CO?2?, whereas differences in CaCO? particle size did not affect the in vitro degradation rate under accelerated conditions.     

In vivo cell interactions with calcium phosphate bioceramics

Biointegration, resorption process, and solubility in physiological environments of calcium phosphate materials are scarcely described by ultrastructural studies. In vivo cells interactions with calcium phosphate materials are scarcely described by ultrastructural studies. In vivo cells interactions with calcium phosphate biomaterials are mediated by different proteins from physiological fluid, and in order to observe at the ultrastructural level the cell colonization, the resorption, process and the biointegration, we used in these experiments calcium phosphate materials precoated with fibronectin or not precoated. Two kinds of well determined materials were used for this study, Beta-tricalcium phosphate (B-TCP) and hydroxyapatite (HAP). The implants were soaked in human fibronectin diluted solution and were implanted in the connective tissue of rabbit abdomen. Our results showed that the fibroblasts and macrophagous++ cells interaction with the calcium phosphate crystal (B-TCP and HAP) was more important in the experiments with a fibronectin bilayer. In the presence of fibronectin at the grains surface of the material, cystic cavities' or fibrous encapsulation was suppressed and cells with fibers were in close contact with the material. The presence of fibronectin immediately after implantation seemed to increase the adhesion and the cell colonization. Fibronectin creates an organic interface between crystals and cells, and can promote interactions from cells and biomaterials.     

Characterization of calcium phosphate cements modified by addition of amorphous calcium phosphate

In this study the influence of amorphous calcium phosphate (ACP) on the setting of, and the formed apatite crystallite size in, a calcium phosphate cement (CPC) based on α-tricalcium phosphate (α-TCP) or tetracalcium phosphate (TTCP)/monocalcium phosphate monohydrate (MCPM) was investigated. Setting times at 22 °C were measured in air atmosphere; those at 37 °C were measured at 100% relative humidity. The phase composition of the set cements was investigated after 1 week using X-ray diffractometry and infrared spectroscopy and the morphology was investigated using scanning electron microscopy. The compressive strength (CS) of the set CPCs was measured after 1 day. Viability of MC3T3-E1 cells on the CPCs was analyzed after 7, 14 and 21 days of incubation using the CellTiter 96^® Aqueous Non-Radioactive Cell Proliferation Assay. The α-TCP-based cement exhibited long setting times, a high CS and was converted to a calcium-deficient hydroxyapatite (CDHAp). The TTCP/MCPM-based CPC was only partly converted to CDHAp, produced acceptable setting times and had a low CS. Addition of ACP to these two CPCs resulted in cements that exhibited good setting times, CS suitable for non-load-bearing applications and a full conversion to nanocrystalline CDHAp. Moreover, the ACP containing CPCs demonstrated good cell viability, making them suitable candidates for bone substitute materials.     

Frozen delivery of brushite calcium phosphate cements

Calcium phosphate cements typically harden following the combination of a calcium phosphate powder component with an aqueous solution to form a matrix consisting of hydroxyapatite or brushite. The mixing process can be very important to the mechanical properties exhibited by cement materials and consequently when used clinically, since they are usually hand-mixed their mechanical properties are prone to operator-induced variability. It is possible to reduce this variability by pre-mixing the cement, e.g. by replacing the aqueous liquid component with non-reactive glycerol. Here, for the first time, we report the formation of three different pre-mixed brushite cement formulations formed by freezing the cement pastes following combination of the powder and liquid components. When frozen and stored at -80 degrees C or less, significant degradation in compression strength did not occur for the duration of the study (28 days). Interestingly, in the case of the brushite cement formed from the combination of beta-tricalcium phosphate with 2 M orthophosphoric acid solution, freezing the cement paste had the effect of increasing mean compressive strength fivefold (from 4 to 20 MPa). The increase in compression strength was accompanied by a reduction in the setting rate of the cement. As no differences in porosity or degree of reaction were observed, strength improvement was attributed to a modification of crystal morphology and a reduction in damage caused to the cement matrix during manipulation.     

In vivo bone regeneration with injectable calcium phosphate biomaterial: a three-dimensional micro-computed tomographic, biomechanical and SEM study

This in vivo study investigated the efficiency of an injectable calcium phosphate bone substitute (IBS) for bone regenerative procedures through non-destructive three-dimensional (3D) micro-tomographic (microCT) imaging, biomechanical testing with a non-destructive micro-indentation technique and 2D scanning electron microscopy (SEM) analysis. The injectable biomaterial was obtained by mixing a biphasic calcium phosphate (BCP) ceramic mineral phase and a cellulosic polymer. The BCP particles were 200-500 microm or 80-200 microm in diameter. The injectable material was implanted for 6 weeks into critical-sized bone defects at the distal end of rabbit femurs. Extensive new bone apposition was noted with both 2D and 3D techniques. Micro-CT showed that newly formed bone was in perfect continuity with the trabecular host bone structure and demonstrated the high interconnectivity of the restored bone network. For both IBS formulations, SEM and microCT gave very close measurements. The only detected significant difference concerned the amount of newly formed bone obtained with IBS 80-200 that appeared significantly higher with microCT analysis than with SEM (p=0.00007). Student t-tests did not show any significant difference in the amount of newly formed bone and remaining ceramic obtained from microCT analysis or SEM. Regression analysis showed satisfactory correlation between both the amount of newly formed bone and remaining ceramic obtained from microCT or SEM. For IBS 200-500, the newly formed bone rate inside the defect was 28.0+/-5.2% with SEM and yield strength of the samples was 18.8+/-5.4 MPa. For IBS 80-200, the newly formed bone rate inside the defect was 31.7+/-5.1% with SEM and yield strength of the samples was 26.8+/-4.5 MPa. Yield strength appeared well correlated with the amount of newly formed bone, specially observed with microCT. This study showed the ability of non-destructive techniques to investigate biological and mechanical aspects of bone replacement with injectable biomaterials.     

Cephalexin-loaded injectable macroporous calcium phosphate bone cement

Different types of calcium phosphate cements (CPCs) have been studied as potential matrices for incorporating different types of antibiotics. All of these matrices were morphologically microporous whereas macroporosity is essential for rapid cement resorption and bone replacement. In this study, liberation of cephalexin monohydrate (CMH) from a macroporous CPC was investigated over 0.5-300 h in simulated body fluid and some mathematical models were fitted to the release profiles. Macroporosity was introduced into the cement matrix by using sodium dodecyl sulfate molecules as air-entraining agents and the effect of both surfactant and CMH on basic properties of the CPC was studied. Incorporation of CMH into the CPC composition increased the setting time, decreased the crystallinity of the formed apatite phase, and improved the injectability of the paste. The use of both CMH and sodium dodecyl sulfate did not affect the rate of conversion of the reactants into apatite phase while soaking the cements in simulated body fluid. Results showed that the liberation rate of the drug from porous CPC was higher than that of the nonporous CPC but same release patterns were experienced in both types of cements, that is, like to nonporous CPC, a time-dependent controlled release of the incorporated drug was obtained from macroporous CPC. The Weibull model was the best fitting-equation for release profiles of all cements. The liberated CMH was as active as fresh cephalexin. It is concluded that this macroporous CPC can be successfully used as drug carrier with controlled release profile for the treatment of bone infections.     

In vivo bone response to porous calcium phosphate cement

We conducted an in vivo experiment to evaluate the resorption rate of a calcium phosphate cement (CPC) with macropores larger than 100 microm, using the CPC called Biocement D (Merck Biomaterial, Darmstadt, Germany), which after setting only shows pores smaller than 1 microm. The gas bubble method used during the setting process created macroporosity. Preset nonporous and porous cement implants were inserted into the trabecular bone of the tibial metaphysis of goats. The size of the preset implants was 6 mm and the diameter of the drill hole was 6.3 mm, leaving a gap of 0.3 mm between implant surface and drill wall. After 2 and 10 weeks, the animals were euthanized and cement implants with surrounding bone were retrieved for histologic evaluation. Light microscopy at 2 weeks revealed that the nonporous implants were surrounded by connective tissue. On the cement surface, we observed a monolayer of multinucleated cells. Ten weeks after implantation, the nonporous implants were still surrounded by connective tissue. However, a thin layer of bone now covered the implant surface. No sign of cement resorption was observed. In contrast, the porous cement evoked a completely different bone response. At 2 weeks, bone formation had already occurred inside the implant porosity. Bone formation even appeared to occur as a result of osteoinduction. Also, at their outer surface, the porous implants were completely surrounded by bone. At 2 weeks, about 31% of the initial cement was resorbed. After 10 weeks, 81% of the initial phosphate cement was resorbed and new bone was deposited. On the basis of these observations, we conclude that the creation of macropores can significantly improve the resorption rate of CPC. This increased degradation is associated with almost complete bone replacement.     

Fibre-reinforced calcium phosphate cements: a review

Calcium phosphate cements (CPC) consist of one or more calcium orthophosphate powders, which upon mixing with water or an aqueous solution, form a paste that is able to set and harden after being implanted within the body. Different issues remain still to be improved in CPC, such as their mechanical properties to more closely mimic those of natural bone, or their macroporosity to favour osteointegration of the artificial grafts. To this end, blends of CPC with polymer and ceramic fibres in different forms have been investigated. The present work aims at providing an overview of the different approaches taken and identifying the most significant achievements in the field of fibre-reinforced calcium phosphate cements for clinical applications, with special focus on their mechanical properties.