Novel magnesium phosphate cements with high early strength and antibacterial properties

Magnesium phosphate cements (MPCs) have been extensively used as fast setting repair cements in civil engineering. They have properties that are also relevant to biomedical applications, such as fast setting, early strength acquisition and adhesive properties. However, there are some aspects that should be improved before they can be used in the human body, namely their highly exothermic setting reaction and the release of potentially harmful ammonia or ammonium ions. In this paper a new family of MPCs was explored as candidate biomaterials for hard tissue applications. The cements were prepared by mixing magnesium oxide (MgO) with either sodium dihydrogen phosphate (NaH(2)PO(4)) or ammonium dihydrogen phosphate (NH(4)H(2)PO(4)), or an equimolar mixture of both. The exothermia and setting kinetics of the new cement formulations were tailored to comply with clinical requirements by adjusting the granularity of the phosphate salt and by using sodium borate as a retardant. The ammonium-containing MPC resulted in struvite (MgNH(4)PO(4)·6H(2)O) as the major reaction product, whereas the MPC prepared with sodium dihydrogen phosphate resulted in an amorphous product. Unreacted magnesium oxide was found in all the formulations. The MPCs studied showed early compressive strengths substantially higher than that of apatitic calcium phosphate cements. The Na-containing MPCs were shown to have antibacterial activity against Streptococcus sanguinis, which was attributed to the alkaline pH developed during the setting reaction.     

钾盐型磷酸镁水泥作为新一代骨骼系统修复材料的研究与应用进展

钾盐型磷酸镁水泥（MKPC）于2009年作为骨修复材料获得美国FDA的认证,目前已在美国临床使用.这种生物材料具有强大的黏合性,能把骨、韧带和肌腱黏附到骨;同时还具有良好的生物相容性、适度的生物降解性和成骨活性,是目前惟一既具有黏合性又具有成骨活性的骨修复材料.此新型材料进入临床必将给骨外科及其相关学科的治疗带来前所未有的改变.概述了MKPC的发展、组成与制备特点、反应机制、应用研究以及具有的优势.     

Combined effect of strontium and pyrophosphate on the properties of brushite cements

In this study we report the synthesis of strontium-containing brushite cement with good cohesion and a diametral tensile strength (DTS) of 5 MPa. The cement powder, composed of β-tricalcium phosphate (β-TCP) and monocalcium phosphate, was adjusted by different concentrations of strontium and pyrophosphate ions. The cement liquid phase was 2 M phosphoric acid solution. The cement cohesion and mechanical properties were measured after being aged in water for 24 h at 37 °C. It was found that at low concentration both strontium and pyrophosphate ions inhibit the cement setting reaction. However, the final setting time was significantly reduced when SrCl₂ increased from 5 to 10 wt.% at pyrophosphate concentrations equal to or higher than 2.16 wt.%. The incorporation of strontium ions did not increase the DTS of brushite cements significantly. In contrast, the addition of pyrophosphate ions did increase the DTS of brushite cements significantly. When both ions were added simultaneously, the brushite cement with a Sr²⁺ content of 5 wt.% had the highest DTS value. Nevertheless, the DTS values of Sr-containing cements were significantly reduced if the pyrophosphate concentration was higher than 2.16 wt.%. The Sr²⁺ ions had a negative effect on brushite cement cohesion, although the solid weight loss started to decrease at Sr²⁺ concentrations higher than 5 wt.%.     

Calcium phosphate cements for bone substitution: Chemistry,handling and mechanical properties

Since their initial formulation in the 1980s, calcium phosphate cements (CPCs) have been increasingly used as bone substitutes. This article provides an overview on the chemistry, kinetics of setting and handling properties (setting time, cohesion and injectability) of CPCs for bone substitution, with a focus on their mechanical properties. Many processing parameters, such as particle size, composition of cement reactants and additives, can be adjusted to control the setting process of CPCs, concomitantly influencing their handling and mechanical performance. Moreover, this review shows that, although the mechanical strength of CPCs is generally low, it is not a critical issue for their application for bone repair – an observation not often realized by researchers and clinicians. CPCs with compressive strengths comparable to those of cortical bones can be produced through densification and/or homogenization of the cement matrix. The real limitation for CPCs appears to be their low fracture toughness and poor mechanical reliability (Weibull modulus), which have so far been only rarely studied.     

黏结剂不同使用方式对全酸蚀树脂水门汀与牙本质间黏结性能的影响

背景：在临床治疗过程中,修复体连同黏结材料一同脱落及产生微小渗孔等情况常有发生,因此,探究黏结剂不同使用方式对全酸蚀树脂水门汀与牙本质间黏结性能的影响具有重要的临床意义。 目的：对比黏结剂不同使用方式对全酸蚀树脂水门汀与牙本质间黏结性能的影响。 方法：获取无龋人新鲜拔除的第二磨牙90颗,随机均分为3组,均于常温水冲洗下打磨消除牙冠部位牙釉质,露出牙本质以制备标准黏结面,分别进行不使用黏结剂处理(对照组)、使用经过光照的全酸蚀树脂水门汀处理(实验2组)、使用未经过光照的全酸蚀树脂水门汀处理(实验1组),检测处理后即刻、处理后再经老化处理的微拉伸黏结强度。 结果与结论：处理后即刻,对照组、实验1组、实验2组的微拉伸黏结强度分别为(8.089±3.431),(11.671±2.561),(8.821±2.513) MPa,组间两两比较差异均有显著性意义(P < 0.05);处理后再经老化处理,对照组、实验1组、实验2组的微拉伸黏结强度分别为(1.069±0.421),(7.621±2.061),(4.821±1.513) MPa,组间两两比较差异均有显著性意义(P < 0.05)。表明全酸蚀树脂水门汀与牙本质的结合在黏结剂不同方法的使用中,无论长期还是短期均是使用不光照处理的黏结剂效果最佳。 中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

A theranostic agent to enhance osteogenic and magnetic resonance imaging properties of calcium phosphate cements

With biomimetic biomaterials, like calcium phosphate cements (CPCs), non-invasive assessment of tissue regeneration is challenging. This study describes a theranostic agent (TA) to simultaneously enhance both imaging and osteogenic properties of such a bone substitute material. For this purpose, mesoporous silica beads were produced containing an iron oxide core to enhance bone magnetic resonance (MR) contrast. The same beads were functionalized with silane linkers to immobilize the osteoinductive protein BMP-2, and finally received a calcium phosphate coating, before being embedded in the CPC. Both in vitro and in vivo tests were performed. In vitro testing showed that the TA beads did not interfere with essential material properties like cement setting. Furthermore, bioactive BMP-2 could be efficiently released from the carrier-beads. In vivo testing in a femoral condyle defect rat model showed long-term MR contrast enhancement, as well as improved osteogenic capacity. Moreover, the TA was released during CPC degradation and was not incorporated into the newly formed bone. In conclusion, the described TA was shown to be suitable for longitudinal material degradation and bone healing studies.     

The importance of surface area in the cytotoxicity of zinc phosphate and silicate cements in vitro

Increasing the surface area of similar volumes of zinc phosphate and silicate cements results in an increase in the in vitro cytotoxicity of these materials. In general there was a proportionate decrease in cellular β-galactosidase and LDH levels with a corresponding rise in supernatant levels. Mouse macrophages were more sensitive than hamster fibroblasts. Enzyme cytochemistry demonstrated a labilization of lysosomal and a stabilization of mitochondrial membranes. pH changes were negligible and did not appear to account for the changes observed.     

Relevance of microstructure for the early antibiotic release of fresh and pre-set calcium phosphate cements

Calcium phosphate cements (CPCs) have great potential as carriers for controlled release and vectoring of drugs in the skeletal system. However, a lot of work still has to be done in order to obtain reproducible and predictable release kinetics. A particular aspect that adds complexity to these materials is that they cannot be considered as stable matrices, since their microstructure evolves during the setting reaction. The aims of the present work were to analyze the effect of the microstructural evolution of the CPC during the setting reaction on the release kinetics of the antibiotic doxycycline hyclate and to assess the effect of the antibiotic on the microstructural development of the CPC. The incorporation of the drug in the CPC modified the textural and microstructural properties of the cements by acting as a nucleating agent for the heterogeneous precipitation of hydroxyapatite crystals, but did not affect its antibacterial activity. In vitro release experiments were carried out on readily prepared cements (fresh CPCs), and compared to those of pre-set CPCs. No burst release was found in any formulation. A marked difference in release kinetics was found at the initial stages; the evolving microstructure of fresh CPCs led to a two-step release. Initially, when the carrier was merely a suspension of α-TCP particles in water, a faster release was recorded, which rapidly evolved to a zero-order release. In contrast, pre-set CPCs released doxycycline following non-Fickian diffusion. The final release percentage was related to the total porosity and entrance pore size of each biomaterial.     

Calcium phosphate cements: action of setting regulators on the properties of the β-tricalcium phosphate-monocalcium phosphate cements

Various additives were tested as setting retarders of the β-tricalcium phosphate-monocalcium phosphate monohydrate (β-TCP-MCPM) cements. Calcium pyrophosphate (CPP), calcium sulphate dihydrate (CSD) and calcium sulphate hemihydrate (CSH) were found to increase the setting time from 30 s to about 10 min. Moreover, the use of CSH resulted in a marked increase of the final diametral strength of the cement, which could be raised from 1MPa to about 3 MPa. The best results were obtained when CSH and CPP were added together to the cement, while the addition of CSD and CPP alone only retarded the setting, without improving the final strength. A particular cement composition (64 wt% β-TCP, 16 wt% MCPM, 15 wt% CSH and 5 wt% CPP), selected for its optimum final strength, was aged in vitro for 8 d at 37°C in saline solution (0.9 wt% NaCl in water). After a moderate decrease, the diametral strength of the specimen was found to level off at about 60% of its initial value (3.2 MPa), for ageing times beyond 1d. This behaviour has been ascribed to the progressive dissolution of the CSD fraction of the hardened cement, compensated by the crystallization of further amounts of DCPD.     

Biomimetic coating of magnesium alloy for enhanced corrosion resistance and calcium phosphate deposition

Degradable metals have been suggested as biomaterials with revolutionary potential for bone-related therapies. Of these candidate metals, magnesium alloys appear to be particularly attractive candidates because of their non-toxicity and outstanding mechanical properties. Despite their having been widely studied as orthopedic implants for bone replacement/regeneration, their undesirably rapid corrosion rate under physiological conditions has limited their actual clinical application. This study reports the use of a novel biomimetic peptide coating for Mg alloys to improve the alloy corrosion resistance. A 3DSS biomimetic peptide is designed based on the highly acidic, bioactive bone and dentin extracellular matrix protein, phosphophoryn. Surface characterization techniques (scanning electron microscopy, energy dispersive X-ray spectroscopy and diffuse-reflectance infrared spectroscopy) confirmed the feasibility of coating the biomimetic 3DSS peptide onto Mg alloy AZ31B. The 3DSS peptide was also used as a template for calcium phosphate deposition on the surface of the alloy. The 3DSS biomimetic peptide coating presented a protective role of AZ31B in both hydrogen evolution and electrochemical corrosion tests.     

不同树脂粘接剂对纤维桩粘接强度及断裂界面的作用

背景：树脂类粘接剂粘接纤维桩的良好性能已被肯定,但不同种类树脂粘接剂的粘接性能不同。 目的：比较Bisco One-step、Clearfil DC及3M RelyX Unicem三种树脂粘接系统对纤维桩的剪切粘接强度,研究纤维桩与根管壁牙本质间的粘接性能。 方法：将15颗人离体牙在釉牙骨质界冠方1 mm处与牙体长轴方向垂直去除牙冠,磨平,常规热牙胶技术根管治疗后,随机分为3组,分别采用Bisco One-step、Clearfil DC及3M RelyX Unicem树脂粘接剂将玻璃纤维桩黏固于根管内,包埋后分别切片制备2 mm厚的样本,采用微推出法测试各组样本的粘接剪切强度;在高倍显微镜下观察所有被测样本的破坏类型。 结果与结论：Bisco One-step粘接剂组、Clearfil DC粘接剂组及3M RelyX Unicem粘接剂组的粘接强度分别为(4.69±1.85),(6.10±0.36),(7.04±0.92) MPa,Bisco One-step粘接剂组粘接强度与Clearfil DC粘接剂组、3M RelyX Unicem粘接剂组比较差异有显著性意义(P < 0.05),Clearfil DC粘接剂组粘接强度与3M RelyX Unicem粘接剂组比较差异无显著性意义。所有样本均主要为Ⅱ,Ⅳ型破坏,即脱出的桩表面完全被粘接剂覆盖或根管壁及桩表面均有部分粘接剂覆盖。表明3种粘接系统对纤维桩粘接强度差异显著,根管壁牙本质-粘接树脂界面是粘接薄弱环节。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程全文链接：     

Immediate and delayed micro-tensile bond strength of different luting resin cements to different regional dentin

We sought to evaluate immediate and delayed micro-tensile bond strength of Panavia F2.0 and Multilink Sprint resin cement to superficial, deep and cervical dentin. Thirty-six freshly extracted non-carious human molars were sectioned in the mesiodistal direction to expose three different dentin regions including superficial dentin (1 mm below the dentine-enamel junction), deep dentin (1 mm above the highest pulp horn) and cervical dentin (0.5 mm above the cemento-enamel junction and 0.5 mm below the dentine-enamel junction). Resin cements were applied on dentin surfaces and composite blocks were luted under constant seating pressure. Each group was divided into three subgroups according to time intervals. Specimens were sectioned to obtain sticks of 1 mm² in diameter and subjected to microtensile bond strength testing at a cross head speed of 1 mm/min. Both resin cements showed higher micro-tensile bond strength to superficial dentin than that to deep or cervical dentin (P < 0.001). Micro-tensile bond strengths of Panavia F2.0 were higher than those of Multilink Sprint at different dentin regions (P < 0.001). Immediate micro-tensile bond strengths were higher than those of delayed micro-tensile bond strengths for both resin cements (P < 0.001). It was concluded that resin cements with different chemical formulations and applications yield significantly different micro-tensile bond strengths to different dentin regions.     

Influence of a novel radiopacifier on the properties of an injectable calcium phosphate cement

An injectable calcium phosphate cement (CPC) with excellent radiopacity was proposed by introducing a novel radiopacifier, strontium carbonate, into the powder phase of CPC. The results showed that the cement showed improved radiopacity even when the content of strontium carbonate was only 8 or 12wt.%. The addition of 8 or 12wt.% strontium carbonate clearly improved the injectability and compressive strength of the cement. Furthermore, the addition of strontium carbonate influenced the pore distribution in the cement. An injectable CPC containing 8 or 12wt.% strontium carbonate has the potential for use in procedures such as vertebroplasty and kyphoplasty.     

A novel and easy-to-prepare strontium(II) modified calcium phosphate bone cement with enhanced mechanical properties

The aim of this study was to evaluate two different approaches to obtaining strontium-modified calcium phosphate bone cements (SrCPCs) without elaborate synthesis of Sr-containing calcium phosphate species as cement precursors that could release biologically effective doses of Sr²⁺ and thus could improve the healing of osteoporotic bone defects. Using strontium carbonate as a strontium(II) source, it was introduced into a hydroxyapatite-forming cement either by the addition of SrCO₃ to an α-tricalcium phosphate-based cement precursor mixture (A-type) or by substitution of CaCO₃ by SrCO₃ during precursor composition (S-type). The cements, obtained after setting in a water-saturated atmosphere, contained up to 2.2 at.% strontium in different distribution patterns as determined by time-of-flight secondary ion mass spectrometry and energy-dispersive X-ray spectroscopy. The setting time of CPC and A-type cements was in the range of 6.5–7.5 min and increased for substitution-type cements (12.5–13.0 min). Set cements had an open porosity between 26 and 42%. Compressive strength was found to increase from 29 MPa up to 90% in substituted S-type cements (58 MPa). SrCPC samples released between 0.45 and 1.53 mg g^?1 Sr²⁺ within 21 days and showed increased radiopacity. Based on these findings, the SrCPC developed in this study could be beneficial for the treatment of defects of systemically impaired (e.g. osteoporotic) bone.     

Controlling initial biodegradation of magnesium by a biocompatible strontium phosphate conversion coating

A simple strontium phosphate (SrP) conversion coating process was developed to protect magnesium (Mg) from the initial degradation post-implantation. The coating morphology, deposition rate and resultant phases are all dependent on the processing temperature, which determines the protective ability for Mg in minimum essential medium (MEM). Coatings produced at 80 °C are primarily made up of strontium apatite (SrAp) with a granular surface, a high degree of crystallinity and the highest protective ability, which arises from retarding anodic dissolution of Mg in MEM. Following 14 days’ immersion in MEM, the SrAp coating maintained its integrity with only a small fraction of the surface corroded. The post-degradation effect of uncoated Mg and Mg coated at 40 and 80 °C on the proliferation and differentiation of human mesenchymal stem cells was also studied, revealing that the SrP coatings are biocompatible and permit proliferation to a level similar to that of pure Mg. The present study suggests that the SrP conversion coating is a promising option for controlling the early rapid degradation rate, and hence hydrogen gas evolution, of Mg implants without adverse effects on surrounding cells and tissues.     

Intrinsic porosity of calcium phosphate cements and its significance for drug delivery and tissue engineering applications

One key point in the field of tissue engineering and drug delivery is to provide materials with an adequate porosity. Many events, including nutrient and waste exchange in scaffolds for tissue engineering, as well as the drug-loading capacity and control of the release rate in drug delivery systems, are controlled by the size, shape and distribution of the pores in the material. Calcium phosphate cements (CPCs) possess an intrinsic porosity that is highly suited for these applications, and this porosity can be controlled by modifying some processing parameters. The objective of this work was to characterize and control the intrinsic porosity of α-tricalcium phosphate (α-TCP) cements, and to investigate its role against adsorption of bovine serum albumin (BSA). Cements with different percentages of open porosity (35–55%) were prepared by modifying the liquid-to-powder ratio. In addition, two different TCP particles were used to yield cements with specific surface areas of 20 and 37 m² g⁻¹. Mercury porosimetry analysis on the set cements showed in most cases a bimodal pore size distribution which varied with the processing parameters and affected differently the adsorption and penetration of BSA. The peak occurring at larger pore dimensions controlled the penetration of BSA and was ascribed to the voids generated in between crystal aggregates, while the peak appearing at lower pore sizes was believed to be due to the intercrystallite voids within aggregates. It was found that, at the concentrations studied, the high intrinsic porosity in CPC does not ensure protein penetration unless there is an adequate pore size distribution.     

The dissolution mechanisms of silicate and glass-ionomer dental cements

The mechanism of dissolution of two dental cements of the acid-base setting types (silicate and glassionomer) is considered. Dissolution is incongruent, probably because most of the leached species can derive both from the matrix (polysalt gel) and the partly reacted glass particles. The release occurs by means of three discrete mechanisms, surface wash-off, diffusion through pores and cracks or diffusion through the bulk. Such behaviour is shown to be capable of being modelled with extremely high goodness-of-fit values, using equations such as y = const + af1/4 + bt. Analogies with research from the fields of geochemistry and nuclear fuel storage are made and these systems obey similar relationships. The dental cement systems differ, however, in that their dissolution is to some extent reversible. This is explained in terms of formation of insoluble complexes, either by reaction of the constituent ions, or by replacement of OH⁻, for example, with F⁻.     

Enhanced antibacterial properties,biocompatibility, and corrosion resistance of degradable Mg-Nd-Zn-Zr alloy

Magnesium (Mg), a potential biodegradable material, has recently received increasing attention due to its unique antibacterial property. However, rapid corrosion in the physiological environment and potential toxicity limit clinical applications. In order to improve the corrosion resistance meanwhile not compromise the antibacterial activity, a novel Mg alloy, Mg–Nd–Zn–Zr (Hereafter, denoted as JDBM), is fabricated by alloying with neodymium (Nd), zinc (Zn), zirconium (Zr). pH value, Mg ion concentration, corrosion rate and electrochemical test show that the corrosion resistance of JDBM is enhanced. A systematic investigation of the in vitro and in vivo antibacterial capability of JDBM is performed. The results of microbiological counting, CLSM, SEM in vitro, and microbiological cultures, histopathology in vivo consistently show JDBM enhanced the antibacterial activity. In addition, the significantly improved cytocompatibility is observed from JDBM. The results suggest that JDBM effectively enhances the corrosion resistance, biocompatibility and antimicrobial properties of Mg by alloying with the proper amount of Zn, Zr and Nd.     

壳聚糖对纳米碳管／磷酸钙骨水泥性能的影响

通过不同添加方式将壳聚糖与纳米碳管／磷酸钙骨水泥混合，研究壳聚糖对复合材料性能的影响。结果表明：壳聚糖与复合粉体充分混合后，再加入去离子水时，可以更好提高复合材料的弯曲强度，壳聚糖含量为0．5％时可以得到较短的凝固时间和较高的弯曲强度（12．99MPa）。     

Preparation and characterization of a novel strontium-containing calcium phosphate cement with the two-step hydration process

A novel Sr-containing calcium phosphate cement (CPC) with excellent compressive strength, good radiopacity and suitable setting time was developed in this work. The two-step hydration reaction resulted in a high compressive strength, with a maximum of up to 74.9 MPa. Sr was doped into the calcium-deficient hydroxyapatite as a hydrated product during the hydration reaction of the CPC. Because of the existence of Sr element and the compact microstructure after hydration, the Sr-containing CPC shows good radiopacity. It is expected to be used in orthopedic and maxillofacial surgery for bone defects repairing.