Load-bearing behavior of a simulated craniofacial structure fabricated from a hydroxyapatite cement and bioresorbable fiber-mesh

Calcium phosphate cements (CPC) have proven successful in the repair of small, non-stress bearing skeletal defects. These cements do not have sufficient tensile strength or fracture toughness to allow their use in stress-bearing applications. It was hypothesized that a bioresorbable fiber mesh would improve the load-bearing behavior of shell structures fabricated of CPC. This study used a biaxial flexure fixture to compare the work-to-fracture values of discs made of: (1) CPC; (2) CPC reinforced with a bioresorbable two-dimensionally oriented poly(glactin) fiber-mesh; and (3) poly(methyl methacrylate) (PMMA) that were immersed in a serum-like solution for 0–28 days. CPC-mesh and PMMA discs were indistinguishable at 0, 1 and 7 days, based on work-to-fracture data. CPC and CPC-mesh discs were indistinguishable at day 28, because of fiber hydrolysis. The knitted fiber-mesh was effective in improving load-bearing behavior of a calcium phosphate cement for potential structural repair of bone defects.     

Mechanical characterisation of a bone defect model filled with ceramic cements

Ceramic bone substitute materials are often used to fill defects in comminuted articular fractures. In an in vivo study [1], calcium phosphate cements have been injected into highly loaded slot defects in the proximal tibial metaphysis. During healing, cracks were formed mostly in the proximal anterior aspect of the implanted cement and wedge-like gaps formed between the tibial plateau and the cement. Mechanical ex vivo tests were done to investigate the mechanical competence of the bone cement in such a defect situation. Entirely filled defects were loaded with up to 4.5 kN until they failed. Cyclic loading of the proximal tibiae caused micro fragmentation of the cement after 1000 cycles at 1.5-2.0 kN load. This aspect was comparable to cement fragmentation observed in vivo. Large defects in highly loaded areas should therefore additionally be stabilised with metallic implants. The ceramic cement can only be used as a filler material, which can be replaced by new bone upon resorption.     

Systematic Assessment of Synthesized Tri-magnesium Phosphate Powders(Amorphous,Semi-crystalline and Crystalline) and Cements for Ceramic Bone Cement Applications

Magnesium phosphate cements have come under investigation in recent years for use as an alternative to calcium phosphate cements for bone void repair applications.Evidence indicates that magnesium phosphate cements obtain higher initial strengths after cement reaction and resorption in more clinically appropriate time frames than commercially available calcium phosphate cements.In this study,amorphous,partially amorphous and crystalline tri-magnesium phosphate powders were synthesized via an aqueous precipitation reaction with subsequent thermal treatment,and characterized using techniques such as X-ray diffraction and Fourier transform infrared spectroscopy.These materials were assessed for their functionality in cementing reaction with a 3.0 mol/L,pH 7.0 ammonium phosphate solution,including setting time and pH evolution in phosphate buffered saline solution.Results indicated that the amorphous and semi-crystalline tri-magnesium phosphate powders were highly reactive with the setting solution but resulted in mechanically weak cements,while the crystalline tri-magnesium phosphate powder reacted efficiently with the cement solution and were mechanically strong following the cement reaction.X-ray diffraction and scanning electron microscopy analyses indicated significant changes in the phase composition and morphology of the cements following incubation in phosphate buffered saline.These were perceived to be detrimental to the integrity of the amorphous and semi-crystalline tri-magnesium phosphate derived cements but not to those created with fully crystalline tri-magnesium phosphate.The crystalline tri-magnesium phosphate material resulted in the most functional cement as this embodiment displayed the most clinically relevant setting time as well as the highest mechanical resilience and neutral pH during incubation in saline solution rendering them potentially viable as bone void fillers.     

Effect of chondroitin sulfate on osteogenetic differentiation of human mesenchymal stem cells

Chondroitin sulfate (CS) has anti-inflammatory properties and increases the regeneration ability of injured bone. In different in vivo investigations on bone defects the addition of CS to calcium phosphate bone cement has lead to an enhanced bone remodeling and increased new bone formation. The goal of this study was to evaluate the cellular effects of CS on human mesenchymal stem cells (hMSCs). In cell culture experiments hMSCs were incubated on calcium phosphate bone cements with and without CS and cultivated in a proliferation and an osteogenetic differentiation media. Alkaline phosphatase and the proliferation rate were determined on days 1, 7 and 14. Concerning the proliferation rates, no significant differences were detected. On days 1, 7 and 14 a significantly higher activity of alkaline phosphatase, an early marker of osteogenesis, was detected around CS modified cements in both types of media. The addition of CS leads to a significant increase of osteogenetic differentiation of hMSCs. To evaluate the influence of the osteoconductive potency of CS in twelve adult male Wistar rats, the interface reaction of cancellous bone to a nanocrystalline hydroxyapatite cement containing type I collagen (CDHA/Coll) without and with CS (CDHA/Coll/CS) was evaluated. Cylindrical implants were inserted press-fit into a defect of the tibial head. 28 days after the operation the direct bone contact and the percentage of newly formed bone were significantly higher on CDHA/Coll/CS-implants (p < 0.05). The addition of CS appears to enhance new bone formation on CDHA/Coll-composites in the early stages of bone healing. Possible mechanisms are discussed.     

PMMA brush-containing two-solution bone cement: preparation, characterization, and influence of composition on cement properties

Two-solution bone cement consisting of poly (methyl methacrylate) (PMMA) brushes in methyl methacrylate has been developed as an alternative to the traditional two-solution (TSBC) and powder-liquid cements. It was hypothesized that the substitution of brushes, for the entire pre-polymer phase of the cement, would permit a decrease in solution viscosity at higher polymer fractions, and allow for physical entanglements with the cement matrix. Consequently, improved cement exothermal and mechanical properties could be expected with brush addition. PMMA brushes were grafted on the surface of cross-linked PMMA nanospheres following a multi-stage synthetic strategy. Brushes exhibiting optimal molecular weight for preparation of TSBC were used for characterization of cement viscosity, flexural and compressive mechanical properties, exothermal properties and residual monomer content. Interactions between grafts and free polymer formed during free radical polymerization of the cement were evaluated based on molecular weight measurements of the cement matrix and brushes. Brush-containing cements exhibited lower viscosity at significantly higher polymer fractions in comparison to TSBC. Cements with PMMA brushes had significantly lower polymerization temperatures and residual monomer content. Measurements of molecular weight revealed the existence of a dry brush regime when using the brush compositions selected in this study, which led to a reduction in the mechanical properties of some of the compositions tested. The optimal cement viscosity and maintenance of other important cement properties achieved with addition of PMMA brushes is expected to expand the use of the two-solution cements in a range of applications.     

Optimisation of the mechanical and handling properties of an injectable calcium phosphate cement

Calcium phosphate cements have the potential to be successful in minimally invasive surgical techniques, like that of vertebroplasty, due to their ability to be injected into a specific bone cavity. These bone cements set to produce a material similar to that of the natural mineral component in bone. Due to the ceramic nature of these materials they are highly brittle and it has been found that they are difficult to inject. This study was carried out to determine the factors that have the greatest effect on the mechanical and handling properties of an apatitic calcium phosphate cement with the use of a Design of Experiments (DoE) approach. The properties of the cement were predominantly influenced by the liquid:powder ratio and weight percent of di-sodium hydrogen phosphate within the liquid phase. An optimum cement composition was hypothesised and tested. The mechanical properties of the optimised cement were within the clinical range for vertebroplasty, however, the handling properties still require improvement.     

Synthesis of bioactive PMMA bone cement via modification with methacryloxypropyltri- methoxysilane and calcium acetate

Bone cement consisting of polymethylmethacrylate (PMMA) powder and methylmethacrylate (MMA) liquid is clinically used for fixation of implants such as artificial hip joints. However, it does not show bone-bonding ability, i.e., bioactivity. The lack of bioactivity would be one of factors which cause loosening between the cement and the implant. The present authors recently showed the potential of bioactive PMMA-based bone cement through modification with γ -methacryloxypropyltrimethoxysilane (MPS) and calcium acetate. In this study, the effects of the kinds of PMMA powder on setting time, apatite formation and compressive strength were investigated in a simulated body fluid (Kokubo solution). The cement modified with calcium acetate calcined at 220 ^∘C could set within 15 min when the PMMA powder had an average molecular weight of 100,000 or less. The addition of calcium acetate calcined at 120 ^∘C in the PMMA powder required a much longer period for setting. The modified cements formed an apatite layer after soaking in the Kokubo solution within 1 day for cement starting from PMMA powder with a molecular weight of 100,000 or less. Compressive strengths of the modified cements were more than 70 MPa for cements starting from 100,000 and 56,000 in molecular weight. After soaking in Kokubo solution for 7 days, the modified cement consisting of PMMA powder of 100,000 in molecular weight showed a smaller decrease in compressive strength than that consisting of 56,000 in molecular weight. These results indicate that bioactive PMMA cement can be produced with appropriate setting time and mechanical strength when PMMA powders with a suitable molecular weight are used. Such a type of design of bioactive PMMA bone cement leads to a novel development of bioactive material for bone substitutes.     

Bone regeneration with glass ceramic implants and calcium phosphate cements in a rabbit cranial defect model

Hydroxyapatite cement (BoneSource®) and brushite calcium phosphate cement (chronOS? Inject) were tested for fixation of glass ceramic implants (Bioverit®) in experimentally created cranial defects in 24 adult New Zealand White rabbits. Aim of the in vivo study was to assess and compare the biocompatibility and osseointegration of the implanted materials. Macroscopic and histological evaluations were performed 1 month, 3 months, and 6 months postoperatively. All implanted materials were well tolerated by the surrounding tissue. Both bone cements exhibited osteoconductive properties. Differences could be detected regarding to the rates of cement resorption and new bone formation. The brushite cement was resorbed faster than the hydroxyapatite cement. The chronOS? Inject samples exhibited a higher rate of connective tissue formation and an insufficient osseointegration. BoneSource® was replaced by bone with minimal invasion of connective tissue. New bone formation occurred faster compared to the chronOS? Inject group. Bioverit® implants fixed with BoneSource® were successfully osseointegrated.     

Bone cements and fillers: A review

Charnley [1] developed the first bone cement in the 1960s using poly(methyl methacrylate) (PMMA), which remains the most widely used material for fixation of orthopaedic joint replacements. In the field of dentistry, zinc polycarboxylate and glass polyalkenoate cements received major research interest from the 1970s to the present day. The discovery of a well-integrated intermediate layer between bone and many bioactive ceramic phases from the calcium–phosphate system, such as hydroxyapatite (HA), resulted in the development of new cements incorporating such phases. These investigations ranged from the development of castable bioactive materials to modified bioactive composites. This paper attempts to give a broad overview of the many different types of cements that have being developed in the past and those which are being researched at the present time. It has lead to a set of fundamental design criteria that should be considered prior to the development of a cement for use as a bone cement or in applications requiring a bone substitute.     

Optimization of benzoyl peroxide concentration in an experimental bone cement based on poly(methyl methacrylate)

The effect of the concentration of benzoyl peroxide in poly(methyl methacrylate) bone cement formulations on their setting characteristics, particularly peak temperature and setting time, were studied. An optimization of the concentration of benzoyl peroxide was made with respect to curing parameters and compared with the residual monomer content. The mechanical properties of the different formulations were also determined and the results indicated that a composition of 1.5% wt/wt and 0.82% wt/wt of benzoyl peroxide and N,N-dimethyl-p-toluidine concentrations, respectively, gave the highest yield strength. Studies on the preparation of bone cement formulations containing different amounts of barium sulphate were also performed to assess the effect on the polymerization process and mechanical properties of the cements.     

Tissue reaction against a self-setting calcium phosphate cement set in bone or outside the organism

Calcium phosphate cements are able to set in situ when injected into bone tissue. We evaluated the tissue reaction occurring when a DCPD-based calcium phosphate cement was either set within the bone or implanted when already set. The samples were implanted in rabbit condyles and examined histologically after 8 and 16 weeks. The relative bone surface, the fibrous capsule around the implants and the implant section surface were measured. Solid material seemed to be better tolerated than paste implants. More bone was found at the solid implant contact whatever the implantation time and the solid material degraded much less rapidly. In conclusion, the physico-chemical modification of the biological environment occurring during setting increases the foreign body reaction against the material.     

Cements from nanocrystalline hydroxyapatite

Calcium phosphate cements are used as bone substitute materials because they may be moulded to fill a void or defect in bone and are osteoconductive. Although apatite cements are stronger than brushite cements, they are potentially less resorbable in vivo. Brushite cements are three-component systems whereby phosphate ions and water react with a soluble calcium phosphate to form brushite (CaHPO4 x 2H2O). Previously reported brushite cement formulations set following the mixture of a calcium phosphate, such as beta-tricalcium phosphate (beta-TCP), with an acidic component such as H3PO4 or monocalcium phosphate monohydrate (MCPM). Due to its low solubility, hydroxyapatite (HA) is yet to be reported as a reactive component in calcium phosphate cement systems. Here we report a new cement system setting to form a matrix consisting predominantly of brushite following the mixture of phosphoric acid with nanocrystalline HA. As a result of the relative ease with which ionic substitutions may be made in apatite this route may offer a novel way to control cement composition or setting characteristics. Since kinetic solubility is dependent on particle size and precipitation temperature is known to affect precipitated HA crystal size, the phase composition and mechanical properties of cements made from HA precipitated at temperatures between 4 and 60 degrees C were investigated.     

Influence of multiwall carbon nanotube functionality and loading on mechanical properties of PMMA/MWCNT bone cements

Poly (methyl methacrylate) (PMMA) bone cement—multi walled carbon nanotube (MWCNT) nanocomposites with weight loadings ranging from 0.1 to 1.0 wt% were prepared. The MWCNTs investigated were unfunctionalised, carboxyl and amine functionalised MWCNTs. Mechanical properties of the resultant nanocomposite cements were characterised as per international standards for acrylic resin cements. These mechanical properties were influenced by the type and wt% loading of MWCNT used. The morphology and degree of dispersion of the MWCNTs in the PMMA matrix at different length scales were examined using field emission scanning electron microscopy. Improvements in mechanical properties were attributed to the MWCNTs arresting/retarding crack propagation through the cement by providing a bridging effect and hindering crack propagation. MWCNTs agglomerations were evident within the cement microstructure, the degree of these agglomerations was dependent on the weight fraction and functionality of MWCNTs incorporated into the cement.     

Injectable collagen/α-tricalcium phosphate cement: collagen–mineral phase interactions and cell response

A bone inspired material was obtained by incorporating collagen in the liquid phase of an α-tricalcium phosphate cement, either in solubilized or in fibrilized form. This material was able to set in situ, giving rise to a calcium deficient hydroxyapatite (CDHA)/collagen composite. The morphology and distribution of collagen in the composite was shown to be strongly affected by the collagen pre-treatment. The interactions between collagen and the inorganic phase were assessed by FTIR. A red shift of the amide I band was indicative of calcium chelation by the collagen carbonyl groups. The rate of CDHA formation was not affected when diluted collagen solutions (1 mg/ml) were used, whereas injectability improved. The presence of solubilized collagen, even in low amount (1 %), increased cell adhesion and proliferation on the composites. Still in the absence of osteogenic medium, significant ALP activity was detected both in the inorganic and the collagen-containing cements. The maximum ALP activity was advanced in the collagen-containing cement as compared to the inorganic cement.     

骨损伤修复用硫酸钙及其无机复合材料的研究进展

创伤、骨肿瘤、关节置换术等引起骨缺损的修复是目前临床治疗的难点和研究热点领域, 寻找理想的骨修复材料已经成为该领域的重点研究方向。硫酸钙骨水泥作为骨修复材料已有百余年历史, 有着显著的优势。但其降解过快的缺点影响了治疗效果, 限制了应用范围。本文对硫酸钙的理化特性、晶粒形貌与晶型控制、合成方法等进行了系统介绍, 总结了硫酸钙与羟基磷灰石、生物玻璃、磷酸钙和硅酸钙复合材料及其性能研究的新成果, 并提出了克服硫酸钙作为骨修复材料的缺点的若干方法。     

Calcium phosphate cement scaffolds with PLGA fibers

The use of calcium phosphate-based biomaterials has revolutionized current orthopedics and dentistry in repairing damaged parts of the skeletal system. Among those biomaterials, the cement made of hydraulic grip calcium phosphate has attracted great interest due to its biocompatibility and hardening “in situ”. However, these cements have low mechanical strength compared with the bones of the human body. In the present work, we have studied the attainment of calcium phosphate cement powders and their addition to poly (co-glycolide) (PLGA) fibers to increase mechanical properties of those cements. We have used a new method that obtains fibers by dripping different reagents. PLGA fibers were frozen after lyophilized. With this new method, which was patented, it was possible to obtain fibers and reinforcing matrix which furthered the increase of mechanical properties, thus allowing the attainment of more resistant materials. The obtained materials were used in the construction of composites and scaffolds for tissue growth, keeping a higher mechanical integrity.     

Relationship between the morphology of PMMA particles and properties of acrylic bone cements

Bone cements are mainly based on acrylie polymers, poly (methyl methacrylate) (PMMA) being the most representative. The curing process (cold curing) is the result of the free radical polymerization of a mixture of beads of PMMA and methyl methacrylate (MMA), initiated by benzoyl peroxide (BPO) and activated by the presence of a tertiary amine, the most classical being N,N-dimethyl-4-toluidine (DMT). In this work the results on the effect of the size and size distribution of PMMA beads and the concentration of DMT and BPO on the setting parameters, the residual monomer content and the mechanical properties (tension and compression) of the cured systems are presented. The use of relatively larger diameter PMMA beads improves the characteristic parameters of the curing process (decreasing the peak temperature and increasing the setting time), without detrimental effects on the mechanical properties of the cured cement.This paper was accepted for publication after the 1995 Conference of the European Society of Biomaterials, Oporio, Portugal, 10–13 September.     

Development of strong and bioactive calcium phosphate cement as a light-cure organic–inorganic hybrid

In this research, light cured calcium phosphate cements (LCCPCs) were developed by mixing a powder phase (P) consisting of tetracalcium phosphate and dicalcium phosphate and a photo-curable resin phase (L), mixture of hydroxyethylmethacrylate (HEMA)/poly acrylic-maleic acid at various P/L ratios of 2.0, 2.4 and 2.8?g/mL. Mechanical strength, phase composition, chemical groups and microstructure of the cured cements were evaluated at pre-set times, i.e. before and after soaking in simulated body fluid (SBF). The proliferation of Rat-derived osteoblastic cells onto the LCCPCs as well as cytotoxicity of cement extracts were determined by cell counting and 3-{4,5-dimethylthiazol-2yl}-2,5-diphenyl-2H-tetrazolium bromide assay after different culture times. It was estimated from Fourier transforming infrared spectra of cured cements that the setting process is ruled by polymerization of HEMA monomers as well as formation of calcium poly-carboxylate salts. Microstructure of the cured cements consisted of calcium phosphate particles surrounded by polymerized resin phase. Formation of nano-sized needlelike calcium phosphate phase on surfaces of cements with P/L ratios of 2.4 and 2.8?g/mL was confirmed by scanning electron microscope images and X-ray diffractometry (XRD) of the cured specimen soaked in SBF for 21?days. Also, XRD patterns revealed that the formed calcium phosphate layer was apatite phase in a poor crystalline form. Biodegradation of the cements was confirmed by weight loss, change in molecular weight of polymer and morphology of the samples after different soaking periods. The maximum compressive strength of LCCPCs governed by resin polymerization and calcium polycarboxylate salts formation was about 80?MPa for cement with P/L ratio of 2.8?g/mL, after incubation for 24?h. The strength of all cements decreased by decreasing P/L ratio as well as increasing soaking time. The preliminary cell studies revealed that LCCPCs could support proliferation of osteoblasts cultured on their surfaces and no cytotoxic effect was observed for the extracts of them.     

Fiber reinforcement of a biomimetic bone cement

In this study we investigated the influence of electrospun polymer fibers on the properties of a α-tricalcium phosphate/gelatin biomimetic cement. To this aim, we added different amounts of poly(L-lactic acid) and poly(lactide-co-glycolide) fibers to the cement composition. Fibers enrichment provoked a significant reduction of both initial and final setting times. Moreover electrospun polymer fibers slowed down the conversion of α-tricalcium phosphate into calcium deficient hydroxyapatite. As a result, the final cements were more compact than the control cement, because of the smaller crystal dimensions and reduced crystallinity of the apatitic phase. The compressive strength, σ(b), and Young's modulus, E, of the control cement decreased significantly after 40 days soaking in physiological solution, whereas the more compact microstructure enabled fiber reinforced cements to maintain their mechanical properties in the long term.     

磷酸钙骨粘合剂的研究

在柠檬酸中添加壳聚糖配成的固化液与磷酸钙骨水泥(CPC)调和制备的骨修复材料具有类似口香糖的胶状特性, 可应用于碎骨粘结, 称之为磷酸钙骨粘合剂(CPCBA)。本研究考察了柠檬酸的含量对抗压强度、固化时间、水化产物和粘结强度的影响, 同时对该体系进行了初步的体外生物学评价。结果显示, 加入柠檬酸可以缩短固化时间并且时间可以通过柠檬酸的含量进行调控, 同时也改善了抗水性能。壳聚糖可以与骨水泥中的钙离子发生螯合作用, 可以增加界面的粘结强度。小鼠原成骨细胞(MC3T3-E1)在其表面粘附良好, 该体系骨水泥有望取代PMMA成为新的骨粘结剂。