Calcium sulphate-based cements containing cephalexin

Cephalexin containing gypsum and apatite/gypsum cements have been synthesised. The presence of cephalexin into the cements does not alter neither the physico-chemical behaviour of the cements nor produce structural changes on them. These cements behave as drug delivery systems when soaked in simulated body fluid. The release of the drug is different depending on the composition. For gypsum cements, the cephalexin is quickly released, helped by a dissolution process of the matrix, whereas the drug release is more controlled by the hydroxyapatite presence in hydroxyapatite/gypsum samples. Apatite containing cements do not only show a different drug release process, also the paste viscosity is lower and a faster formation "in vitro" of an apatite-type layer on their surface is observed.     

Gentamicin-loaded strontium-containing hydroxyapatite bioactive bone cement--an efficient bioactive antibiotic drug delivery system

Modified strontium-containing hydroxyapatite (Sr-HA) bone cement was loaded with gentamicin sulfate to generate an efficient bioactive antibiotic drug delivery system for treatment of bone defects. Gentamicin release and its antibacterial property were determined by fluorometric method and inhibition of Staphylococcus aureus (S. aureus) growth. Gentamicin was released from Sr-HA bone cement during the entire period of study and reached around 38% (w/w) cumulatively after 30 days. Antibacterial activity of the gentamicin loaded in the cements is clearly confirmed by the growth inhibition of S. aureus. The results of the amount and duration of gentamicin release suggest a better drug delivery efficiency in Sr-HA bone cement over polymethylmethacrylate bone cement. Bioactivity of the gentamicin-loaded Sr-HA bone cement was confirmed with the formation of apatite layer with 1.836 ± 0.037 μm thick on day 1 and 5.177 ± 1.355 μm thick on day 7 after immersion in simulated body fluid. Compressive strengths of the gentamicin-loaded Sr-HA cement reached 132.60 ± 10.08 MPa, with a slight decrease from the unloaded groups by 4-9%. Bending moduli of Sr-HA cements with and without gentamicin were 1.782 ± 0.072 GPa and 1.681 ± 0.208 GPa, respectively. On the contrary, unloaded Sr-HA cement obtained slightly larger bending strength of 35.48 ± 2.63 MPa comparing with 33.00 ± 1.65 MPa for loaded cement. No statistical difference was found on the bending strengths and modulus of gentamicin-loaded and -unloaded Sr-HA cements. Sr-HA bone cement loaded with gentamicin was proven to be an efficient drug delivery system with uncompromised mechanical properties and bioactivity.     

Phase evaluation of an effervescent-added apatitic calcium phosphate bone cement

Development of macroporosity during setting would allow fast bone ingrowth and good osteointegration of the implant. The interconnected macropores could be created in calcium phosphate cements (CPCs) through the addition of an effervescent porogen mixture to the component of the cements. But this addition could also affect other characteristics of CPCs, such as setting time, mechanical strength, extent of conversion of reactant to apatite phase, crystallinity, and chemical composition of apatite lattice. In this study, these properties were investigated in an effervescent-added calcium phosphate bone cement. From 0 to 20 wt % of an effervescent mixture was added to calcium phosphate cement (CPC) components and phase evaluations were performed after 24 h incubation at 37 degrees C and 28% relative humidity and 1, 3, 7, and 14 days immersion in a specific simulated body fluid. XRD and FTIR techniques were used to characterize the cement composition, crystallinity, and chemical groups in final CPCs. The results showed that addition of effervescent porogen affects the extent of conversion of reactant to apatite phase and crystallinity. In other words, using the effervescent porogen in CPCs could accelerate the rate of conversion of TTCP/DCPA reactant to apatite phase with smaller crystallites, so that it was the predominant phase (about 67%) after only 3 days soaking in SBF solution. The content of carbonate groups substituted for phosphate groups in apatite lattice increased when the effervescent additive was further added. The compressive strength of the set calcium phosphate cement decreased significantly with the addition of the effervescent agent and reached from 8 MPa for additive-free CPC to 1.3 MPa for 20% effervescent-added CPC. The compressive strength was improved after 3 days immersing of CPC in the simulated body fluid solution.     

Controlled release properties and final macroporosity of a pectin microspheres–calcium phosphate composite bone cement

The use of calcium phosphate cements (CPC) is restricted by their lack of macroporosity and poor drug release properties. To overcome these two limitations, incorporating degradable polymer microparticles into CPC is an attractive option, as polymer microparticles could help to control drug release and induce macroporosity after degradation. Although few authors have yet tested synthetic polymers, the potentiality of polysaccharides’ assuming this role has never been explored. Low-methoxy amidated pectins (LMAP) constitute valuable candidates because of their biocompatibility and ionic and pH sensitivity. In this study, the potentiality of a LMAP with a degree of esterification (DE) of 30 and a degree of amidation (DA) of 19 was explored. The aim of this study was to explore the influence of LMAP microspheres within the composite on the cement properties, drug release ability and final macroporosity after microspheres degradation. Three LMAP incorporation ratios, 2%, 4% and 6% w/w were tested, and ibuprofen was chosen as the model drug. In comparison with the CPC reference, the resulting composites presented reduced setting times and lowered the mechanical properties, which remained acceptable for an implantation in moderate-stress-bearing locations. Sustained release of ibuprofen was obtained on at least 45 days, and release rates were found to be controlled by the LMAP ratio, which modulated drug diffusion. After 4 months of degradation study, the resulting CPC appeared macroporous, with a maximum macroporosity of nearly 30% for the highest LMAP incorporation ratio, and interconnectivity between pores could be observed. In conclusion, LMAP appear as interesting candidates to generate macroporous bone cements with tailored release properties and macroporosity by adjusting the pectin content within the composites.     

PLGA microsphere/calcium phosphate cement composites for tissue engineering: in vitro release and degradation characteristics

Bone cements with biodegradable poly(lactic-co-glycolic acid) (PLGA) microspheres have already been proven to provide a macroporous calcium phosphate cement (CPC) during in situ microsphere degradation. Furthermore, in vitro/in vivo release studies with these PLGA microsphere/CPC composites (PLGA/CPCs) showed a sustained release of osteo-inductive growth factor when drug was distributed inside/onto the microspheres. The goal of this study was to elucidate the mechanism behind drug release from PLGA/CPC. For this, in vitro release and degradation characteristics of a low-molecular-weight PLGA/CPC (M(w) = 5 kg/mol) were determined using bovine serum albumin (BSA) as a model protein. Two loading mechanisms were applied; BSA was either adsorbed onto the microspheres or incorporated inside the microspheres during double-emulsion. BSA release from PLGA microspheres and CPC was also measured and used as reference. Results show fast degrading polymer microspheres which produced a macroporous scaffold within 4 weeks, but also showed a concomitant release of acidic degradation products. BSA release from the PLGA/CPC was similar to the CPC samples and showed a pattern consisting of a small initial release, followed by a period of almost no sustained release. Separate PLGA microspheres exhibited a high burst release and release efficiency that was higher with the adsorbed samples. Combining degradation and release data we can conclude that for the PLGA/CPC samples BSA re-adsorbed to the cement surface after being released from the microspheres, which was mediated by the pH decrease during microsphere degradation.     

Functionalized bridged silsesquioxane-based nanostructured microspheres: performance as novel drug-delivery devices in bone tissue-related applications

Two kinds of functionalized nanostructured hybrid microspheres, based on the bridged silsesquioxane family, were synthesized by employing the sol-gel method via self-assembly of two different organic-inorganic bridged monomers. The architecture reached at molecular level allowed the incorporation of acetylsalicylic acid (ASA) as an anti-inflammatory model drug. The ASA-functionalized microspheres were characterized as delivery devices in simulated body fluid (SBF). The release behaviors of the synthesized microspheres (Fickian or anomalous diffusion mechanisms) were shown to be dependent on the chemical nature of the bridged monomers employed to synthesize the hybrid materials. The functionalized microspheres were proposed as delivery systems into calcium phosphate cements (CPCs), in order to slow down the characteristic drug-delivery kinetics of this kind of bone tissue-related materials. The incorporation of the new functionalized microparticles into the CPCs represented a viable methodology to modify the ASA-release kinetics in comparison to a conventional CPC containing the drug dispersed into the solid phase. The ASA-delivery profiles obtained from the microsphere-loaded CPCs showed that 40-60% of drug can be released after 2 weeks of testing in SBF. The inclusion of the microspheres into the CPC matrices allowed modification of the release profiles through a mechanism that involved two stages: (1) the diffusion of the drug through the organic-inorganic matrix of the microspheres (according to a Fickian or anomalous diffusion, depending on the nanostructuring) and (2) the subsequent diffusion of the drug through the ceramic matrix of the hardened cements. The release behavior of the composite cements was shown to be dependent on the nanostructuring of the hybrid microspheres, which can be selectively tailored by choosing the desired chemical structure of the bridged precursors employed in the sol-gel synthesis. The obtained results demonstrated the ability of this new class of functionalized hybrid microdevices as delivery systems into calcium phosphate materials with potential bone tissue-related drug-delivery applications.     

The influence of the acidic component of the gas-foaming porogen used in preparing an injectable porous calcium phosphate cement on its properties: acetic acid versus citric acid

In the present study, macroporous calcium phosphate cements (CPCs) were prepared using a porogen; that is, the gas-foaming technique. The objective was to investigate the influence of the acidic component of the porogen (acetic acid versus citric acid) on several properties of a specified CPC. In all of the cements prepared, the basic component of the porogen was the same, namely, NaHCO(3), and it was added to the powder phase of the cement, while the acidic component of the porogen was dissolved in the liquid phase of the cement. The cements were characterized in terms of initial setting time, porosity, crystallinity, injectability and compressive strength. Also, XRD, FTIR, and SEM techniques were employed to evaluate the phase composition, the chemical groups and the morphological aspects of the porous cements during setting. It was found that the presence of a porogen in a CPC led to significant decreases in both its initial setting time and compressive strength. A CPC made using acetic acid contained a larger amount of the apatite phase but was significantly less injectable and less porous than when citric acid was used.     

Ready-to-use injectable calcium phosphate bone cement paste as drug carrier

Current developments in calcium phosphate cement (CPC) technology concern the use of ready-to-use injectable cement pastes by dispersing the cement powder in a water-miscible solvent, such that, after injection into the physiological environment, setting of cements occurs by diffusion of water into the cement paste. It has also been demonstrated recently that the combination of a water-immiscible carrier liquid combined with suitable surfactants facilitates a discontinuous liquid exchange in CPC, enabling the cement setting reaction to take place. This paper reports on the use of these novel cement paste formulations as a controlled release system of antibiotics (gentamicin, vancomycin). Cement pastes were applied either as a one-component material, in which the solid drugs were physically dispersed, or as a two-component system, where the drugs were dissolved in an aqueous phase that was homogeneously mixed with the cement paste using a static mixing device during injection. Drug release profiles of both antibiotics from pre-mixed one- and two-component cements were characterized by an initial burst release of ～7–28%, followed by a typical square root of time release kinetic for vancomycin. Gentamicin release rates also decreased during the first days of the release study, but after ～1 week, the release rates were more or less constant over a period of several weeks. This anomalous release kinetic was attributed to participation of the sulfate counter ion in the cement setting reaction altering the drug solubility. The drug-loaded cement pastes showed high antimicrobial potency against Staphylococcus aureus in an agar diffusion test regime, while other cement properties such as mechanical performance or phase composition after setting were only marginally affected.     

Evaluation of a bioceramic-based nanocomposite material for controlled delivery of a non-steroidal anti-inflammatory drug

In this study, nanocomposite of 50 wt% calcium sulfate and 50 wt% nanocrystalline apatite was produced and its biocompatibility, physical and structural properties were compared with pure calcium sulfate (CS) cement. Indomethacin (IM), a non-steroidal anti-inflammatory drug, was also loaded on both CS and nanocomposite cements and its in vitro release was evaluated over a period of time. The effect of the loaded IM on basic properties of the cements was also investigated. Biocompatibility tests showed a partial cytotoxicity in CS cement due to the reduced number of viable mouse fibroblast L929 cells in contact with the samples as well as spherical morphologies of the cells. However, no cytotoxic effect was observed for nanocomposite cement and no significant difference was found between the number of the cells seeded in contact with this specimens and culture plate as control. Other results showed that the setting time and injectability of the nanocomposite cement was much higher than those of CS cement, whereas reverse result obtained for compressive strength. In addition, incorporation of IM into compositions slightly increased the initial setting time and injectability of the cements and did not change their compressive strength. While a fast IM release was observed from CS cement in which about 97% of the loaded drug was released during 48 h, nanocomposite cement showed a sustained release behavior in which 80% of the loaded IM was liberated after 144 h. Thus, the nanocomposite can be a more appropriate carrier than CS for controlled release of IM in bone defect treatments.     

Release profile of antimicrobial agents from alpha-tricalcium phosphate cement.

A new method for treating carious dentine with alpha-tricalcium phosphate (alpha-TCP) dental cement containing antimicrobial agents has been recently introduced. However, the release behavior of antimicrobial agents from this cement has not yet been clarified. The aim of this study is therefore to examine the release profile of the antimicrobial agents from the alpha-TCP cement. Three kinds of antimicrobial agents (metronidazole, cefaclor and ciprofloxacin) were added to two commercially available alpha-TCP cements (new apatite liner type I and type II). The set cements were then immersed in water at 37 degrees C and the released antimicrobial agents and Ca ion were determined at regular intervals for three months. In addition, scanning electron microscopic observations were conducted before and after immersion for three months. The release profile of the cements containing antimicrobial agents varied depending on the types of antimicrobial agents. The incorporation of antimicrobial agents affected the setting reaction of the cements. The release behavior of the drugs also varied depending on the types of the cements. The differences in the release profile between type I and type II cements reflected the structures and compositions of their matrices.     

Loading and release of doxycycline hyclate from strontium-substituted calcium phosphate cement

Novel Sr-substituted calcium phosphate cement (CPC) loaded with doxycycline hyclate (DOXY-h) was employed to elucidate the effect of strontium substitution on antibiotic delivery. The cement was prepared using as reactants Sr-substituted β-tricalcium phosphate (Sr-β-TCP) and acidic monocalcium phosphate monohydrate. Two different methods were used to load DOXY-h: (i) the adsorption on CPC by incubating the set cement in drug-containing solutions; and (ii) the use of antibiotic solution as the cement liquid phase. The results revealed that the Sr-substituted cement efficiently adsorbs the antibiotic, which is attributed to an enhanced accessibility to the drug-binding sites within this CPC. DOXY-h desorption is influenced by the initial adsorbed amount and the cement matrix type. Furthermore, the fraction of drug released from CPCs set with DOXY-h solution was higher, and the release rate was faster for the CPC prepared with 26.7% Sr-β-TCP. The analysis of releasing profiles points to Fickian diffusion as the mechanism responsible for antibiotic delivery. We can conclude that Sr substitution in secondary calcium phosphate cements improves their efficiency for DOXY-h adsorption and release. The antibiotic loading method provides a way to switch from rapid and complete to slower and prolonged drug release.     

Investigation of an effervescent additive as porogenic agent for bone cement macroporosity

Calcium phosphate cements (CPCs) are biocompatible and osteoconductive materials used in dental, craniofacial and orthopaedic applications. One of the most important advantages of these materials is their replacement with bone followed by resorption. Already several attempts have been made to improve the resorption behaviour of calcium phosphate cements by increasing the porosity of the material. In this investigation a mixture of NaHCO(3) and citric acid monohydrate was added to the apatite cement component as an effervescent additive for producing interconnected macropores into the cement matrix. Mercury intrusion porosimetry was employed to determine pore volume and pore size distribution in the calcium phosphate cement (CPC) samples. Results showed that addition of only 10 wt % of the effervescent additive (based on the cement powder) to the CPC components lead to producing about 20 V % macropores (with the size of 10 to 1000 mum) into the cement structure. The setting time was measured in an incubator at 37 degrees C and decreased from 40 min for additive-free CPC to about 14 min for CPC containing effervescent additive. Other properties of the CPCs such as compressive strength, phase composition, microstructure morphology and dissolution behavior were evaluated after immersing them in a simulated body fluid solution. The results showed that the rate of formation of poor crystalline apatite phase have been improved by production of macroporosity into the cement matrix.     

Effects of ceramic component on cephalexin release from bioactive bone cement consisting of Bis-GMA/TEGDMA resin and bioactive glass ceramics

The purpose of this study was to elucidate the effect of amount of ceramic cement powder on drug release from bioactive bone cement. The associated bone-bonding strength was also investigated. The bioactive bone cement under investigation consisted of bisphenol-alpha-glycidyl methacrylate (Bis-GMA), triethylene-glycol dimethacrylate (TEGDMA) resin and a combination of apatite- and wollastonite-containing glass-ceramic (A-W GC) powder. A-W GC powder (50%, 70% and 80% w/w) containing 5% cephalexin (CEX) powder hardened within 5 min after mixing with Bis-GMA/TEGDMA resin. The compressive strength of the cement with or without drug increased with increasing the amount of ceramic powder. The compressive strength of the 80% ceramic cement without the incorporation of cephalexin was 194 MPa. This compressive strength was about 3 times higher than that for polymethylmethacrylate cement. After the cement was implanted in the proximal metaphysis of the tibiae of male rabbits, the failure load for the cement was found to increase with increasing of the amount of ceramic powder. This finding suggested that the cement formed a bonding with bone. In vitro CEX release from bioactive bone cement pellets in a simulated body fluid at pH 7.25 and 37 degrees C continued for more than 2 weeks. Drug release profile followed the Higuchi equation initially, but not at later stages. The drug release rate increased with increasing amount of ceramic powder in the mixture. Since the pore volume of the cement increased with increasing of amount of ceramic powder, the drug diffused in the pores between the ceramics particle and polymer matrix. As hydroxyapatite precipitated on the cement surface, the drug release rate decreased, as observed at the later release stage. These results suggest that varying the amount of ceramic powder in the cement system could control the drug release rate from bioactive bone cement.     

In vitro change in mechanical strength of beta-tricalcium phosphate/copolymerized poly-L-lactide composites and their application for guided bone regeneration

The bone regenerative properties of calcium phosphate cements (CPCs) may be improved by the addition of growth factors, such as recombinant human transforming growth factor-beta1 (rhTGF-beta1). Previously, we showed that rhTGF-beta1 in CPC stimulated the differentiation of preosteoblastic cells from adult rat long bones. The intermixing of rhTGF-beta1 in CPC, which was subsequently applied to rat calvarial defects, enhanced bone growth around the cement and increased the degradation of the cement. However, it is unknown whether the addition of rhTGF-beta1 changes the material properties of CPC and what the characteristics of the release of rhTGF-beta1 from CPC are. Therefore, we determined in this study the release of rhTGF-beta1, in vitro, from the cement pellets as implanted in the rat calvariae. The possible intervening effects of rhTGF-beta1 intermixing on the clinical compliance of CPC were studied through an assessment of its compressive strength and setting time, as well as its crystallinity, calcium-to-phosphorus ratio, porosity, and microscopic structure. We prepared CPC by mixing calcium phosphate powder (58% alpha-tricalcium phosphate, 25% anhydrous dicalcium phosphate, 8.5% calcium carbonate, and 8.5% hydroxyapatite) with a liquid (3 g/mL). The liquid for standard CPC consisted of water with 4% disodium hydrogen phosphate, whereas the liquid for modified CPC was mixed with an equal amount of 4 mM hydrochloride with 0.2% bovine serum albumin. The hydrochloride liquid contained rhTGF-beta1 in different concentrations for the release experiments. Most of the rhTGF-beta1 incorporated in the cement pellets was released within the first 48 h. For all concentrations of intermixed rhTGF-beta1 (100 ng to 2.5 mg/g of CPC), approximately 0.5% was released in the first 4 h, increasing to 1.0% after 48 h. Further release was only about 0.1% from 2 days to 8 weeks. CPC modification slightly increased the initial setting time at 20 degrees C from 2.6 to 5 min but had no effect on the final setting time of CPC at 20 degrees C or the initial and final setting times at 37 degrees C. The compressive strength was increased from 18 MPa in the standard CPC to 28 MPa in the modified CPC only 4 h after mixing. The compressive strength diminished in the modified CPC between 24 h and 8 weeks from 55 to 25 MPa. No other significant change was found with the CPC modification for rhTGF-beta1. X-ray diffraction revealed that standard and modified CPCs changed similarly from the original components, alpha-tricalcium phosphate and anhydrous dicalcium phosphate, into an apatite cement. The calcium-to-phosphorus ratio, as determined with an electron microprobe, did not differ for standard CPC and modified CPC. Standard and modified CPCs became dense and homogeneous structures after 24 h, but the modified CPC contained more crystal plaques than the standard CPC, as observed with scanning electron microscopy (SEM). SEM and back- scattered electron images revealed that after 8 weeks the cements showed equally and uniformly dense structures with microscopic pores (<1 microm). Both CPCs showed fewer crystal plaques at 8 weeks than at 24 h. This study shows that CPC is not severely changed by its modification for rhTGF-beta1. The prolonged setting time of modified cement may affect the clinical handling but is still within acceptable limits. The compressive strength for both standard and modified cements was within the range of thin trabecular bone; therefore, both CPCs can withstand equal mechanical loading. The faster diminishing compressive strength of modified cement from 24 h to 8 weeks likely results in early breakdown and so might be favorable for bone regeneration. Together with the beneficial effects on bone regeneration from the addition of rhTGF-beta1 to CPC, as shown in our previous studies, we conclude that the envisaged applications for CPC in bone defects are upgraded by the intermixing of rhTGF-beta1. Therefore, the combination of CPC and rhTGF-beta1 forms a promising synthetic bone graft.     

Effect of nanostructure on biodegradation behaviors of self-setting apatite/collagen composite cements containing vitamin K2 in rats

Apatite cement and collagen were combined by a mechanochemical method to create a new self-setting apatite/collagen composite cement, and menatetrenone (VK2) was loaded into a drug-delivery system to test biocompatibility in rats. Powder X-ray diffraction analysis (XRD), scanning electron microscopy (SEM), and electron probe microanalyzer (EPMA) were performed to characterize the physicochemical properties of apatite/collagen composite cements. The XRD results suggested that ground apatite/collagen cement was completely transformed into bone-like hydroxyapatite, but that without grinding was incomplete. The SEM and EPMA results suggested that ground apatite/collagen cement was homogeneously dispersed of nanoapatite crystals in collagen matrices, similar to that in natural bone. In contrast, the cement without grinding was heterogeneously distributed. To evaluate in-vivo cement density (CMM), microradiograms were measured for 72 days after implanting apatite/collagen composite cements in intramuscular tissue on the backs of rats, and cross sections of the cements and surrounding soft tissues were observed by microscope. The CMM results of the apatite/collagen composite cements suggested that the biodegradation rate was dependent on the cement quality and nanogeometrical structure. The CMM result of VK2-loaded apatite/collagen cements suggested that the biodegradation rates of the cements were significantly dependent on their formulation. The CMM of ground apatite/collagen cement increased until 7 days and then decreased, and bone-like cells penetrated deeply in the center. The microphotograph and CMM results of apatite/collagen without grinding indicated that a lot of bone-like cells penetrated into the cement and the cement shape was totally deformed.     

Controlled release of gentamicin from calcium phosphate-poly(lactic acid-co-glycolic acid) composite bone cement

Modification of a self setting bone cement with biodegradable microspheres to achieve controlled local release of antibiotics without compromising mechanical properties was investigated. Different biodegradable microsphere batches were prepared from poly(lactic-co-glycolic acid) (PLGA) using a spray-drying technique to encapsulate gentamicin crobefate varying PLGA composition and drug loading. Microsphere properties such as surface morphology, particle size and antibiotic drug release profiles were characterized. Microspheres were mixed with an apatitic calcium phosphate bone cement to generate an antibiotic drug delivery system for treatment of bone defects. All batches of cement/microsphere composites showed an unchanged compressive strength of 60 MPa and no increase in setting time. Antibiotic release increased with increasing drug loading of the microspheres up to 30% (w/w). Drug burst of gentamicin crobefate in the microspheres was abolished in cement/microsphere composites yielding nearly zero order release profiles. Modification of calcium phosphate cements using biodegradable microspheres proved to be an efficient drug delivery system allowing a broad range of 10-30% drug loading with uncompromised mechanical properties.     

Preparation of macroporous calcium phosphate cement tissue engineering scaffold

Unlike sintered hydroxyapatite there is evidence to suggest that calcium phosphate cement (CPC) is actively remodelled in vivo and because CPC is formed by a low-temperature process, thermally unstable compounds such as proteins may be incorporated into the matrix of the cement which can then be released after implantation. The efficacy of a macroporous CPC as a bone tissue engineering scaffold has been reported; however, there have been few previous studies on the effect of macroporosity on the mechanical properties of the CPC. This study reports a novel method for the formation of macroporous CPC scaffolds, which has two main advantages over the previously reported manufacturing route: the cement matrix is considerably denser than CPC formed from slurry systems and the scaffold is formed at temperatures below room temperature. A mixture of frozen sodium phosphate solution particles and CPC powder were compacted at 106 MPa and the sodium phosphate was allowed to melt and simultaneously set the cement. The effect of the amount of porogen used during processing on the porosity, pore size distribution and compressive strength of the scaffold was investigated. It was found that macroporous CPC could reliably be fabricated using cement:ice ratios as low as 5:2.     

Formation of interconnected macropores in apatitic calcium phosphate bone cement with the use of an effervescent additive

Calcium phosphate cements (CPCs) can be considered as good candidate for bone tissue engineering because they can be resorbed and take part in the bone remodeling process. Several efforts have been made into improve the resorption rate of the calcium phosphate cement by introducing macropores to the cement matrix. In this investigation a simple and effective method has been presented based on the addition of various amounts of an effervescent agent to the calcium phosphate cement components. The effervescent agent was a mixture of sodium hydrogen carbonate, NaHCO(3) (that was added to the powder phase), and citric acid monohydrate, C(6)H(8)O(7).H(2)O (that was dissolved in the liquid phase). The obtained macroporous samples were characterized by Fourier transform infrared spectrometer, X-ray diffraction, and scanning electron microscopy techniques at 4 h after setting and 3 days after soaking in a special simulated body fluid solution named Hank's balanced salt solution. Mercury intrusion porosimetry was also employed for characterizing the pore volume and pore size distribution in the cement structure. Results showed that the rate of conversion of staring reactant to the apatite phase and the apatite chemistry were significantly changed by using the additive in the cement components. Also both the pore volume and pore size were changed by varying both the amount of effervescent additive and the powder to liquid ratio.     

载药型磷酸钙骨水泥的制备及体外释放性能

背景：磷酸钙骨水泥具有良好的生物相容性,可作为骨修复材料与药物载体。 目的：制备载药磷酸三钙骨水泥,并分析其体外释放性能。 方法：采用共沉淀法制备磷酸三钙前躯体,经高温煅烧研磨获得α-磷酸三钙粉体,测试含不同浓度(1.25%,2.5%,3.75%,5%)抗生素(头孢拉定或头孢氨苄或环丙沙星)骨水泥,浸泡不同时间后(6 h、12 h、24 h、2 d、3 d、4 d、 5 d、6 d、7 d、8 d)的药物体外释放浓度。 结果与结论：制备的磷酸三钙粉体粒度约2 μm,结晶度良好。载不同抗生素的骨水泥体外释放都受自身物理性质的影响。载药骨水泥中环丙沙星能够满足长时间缓释,并能达到一个比较理想的缓释浓度,头孢类药物由于自身稳定性等原因,缓释效果并不理想。头孢氨苄的水解速率较低,环丙沙星的光降解条件比较苛刻,因此两者释放未受太大影响,与Higuchi模型基本吻合;头孢拉定的水解速率相对较高,对体系的释放驱动力产生较大影响,使得释放不再遵循Higuchi模型。     

骨水泥不同时相负载抗生素

背景：在人工关节置换中,骨水泥与何种抗生素配伍能起到有效预防和治疗置换后感染目前还存在争议。 目的：观察抗生素骨水泥中不同抗生素及不同混合方法对动物体内抗生素释放特性以及骨水泥力学性能的影响。 方法：36只大白兔随机抽签法分为6组,3个实验组在骨水泥固相与液相混合后分别加入2 g硫酸庆大霉素、1 g万古霉素、1.5 g头孢呋辛钠,制成负载抗生素的骨水泥,置于实验兔体内。3个对照组分别在40 g骨水泥固相与液相混合前加入2 g硫酸庆大霉素粉剂、1 g万古霉素粉剂、1.5 g头孢呋辛钠。 结果与结论：3种抗生素在兔体内持续平均释放时间均在31 d以上,骨水泥固相与液相混合后加入抗生素的3组抗生素洗提总量分别高于混合前加入抗生素的3组(P < 0.05),混合后加入万古霉素组的洗提总量高于其他各组(P < 0.05)。各组抗生素骨水泥的力学性能均优于ISO 5833国际标准,组间差异无显著性意义。提示抗生素能有效从骨水泥中释放,骨水泥中加入1.0~2.0 g抗生素不影响骨水泥的机械强度;万古霉素的洗提效果较好;骨水泥固相与液相混合后加入抗生素的混合方法更有利于抗生素的释出。