Premixed macroporous calcium phosphate cement scaffold

Calcium phosphate cement (CPC) sets in situ to form resorbable hydroxyapatite and is promising for orthopaedic applications. However, it requires on-site powder-liquid mixing during surgery, which prolongs surgical time and raises concerns of inhomogeneous mixing. The objective of this study was to develop a premixed CPC scaffold with macropores suitable for tissue ingrowth. To avoid the on-site powder-liquid mixing, the CPC paste was mixed in advance and did not set in storage; it set only after placement in a physiological solution. Using 30% and 40% mass fractions of mannitol porogen, the premixed CPC scaffold with fibers had flexural strength (mean ± sd; n = 5) of (3.9 ± 1.4) MPa and (1.8 ± 0.8) MPa, respectively. The scaffold porosity reached (68.6 ± 0.7)% and (74.7 ± 1.2)%, respectively. Osteoblast cells colonized in the surface macropores of the scaffold and attached to the hydroxyapatite crystals. Cell viability values for the premixed CPC scaffold was not significantly different from that of a conventional non-premixed CPC known to be biocompatible (P > 0.1). In conclusion, using fast-dissolving porogen and slow-dissolving fibers, a premixed macroporous CPC scaffold was developed with strength approaching the reported strengths of sintered porous hydroxyapatite implants and cancellous bone, and non-cytotoxicity similar to a biocompatible non-premixed CPC. Official contribution of the National Institute of Standards and Technology; not subject to copyright in the United States.     

Bone ingrowth in zirconia and hydroxyapatite scaffolds with identical macroporosity

The role of the material composition, porosity and surface topography of scaffolds for promotion of osteogenesis and osseointegration is not fully understood. The aim of the present study was to evaluate the effects of material composition and surface topography on bone ingrowth and bone contact. Designed macroporous ceramic scaffolds of zirconia and hydroxyapatite were used. Using free form fabrication (FFF) techniques an identical macroporosity in both materials was achieved. The scaffolds were implanted in rabbit tibia (cortical bone) and femur (trabecular bone). After 6 weeks of implantation the tissue response was assessed with histology and histomorphometry. The results showed significantly more bone ingrowth and bone contact in the hydroxyapatite scaffolds compared to the zirconia scaffold. Surface topography had no significant effect on bone contact inside the macropores regardless of material. This was observed in both cortical and trabecular bone sites. The study suggests that the difference between hydroxyapatite and zirconia was due to a difference in material chemistry.     

聚乳酸-羟基乙酸共聚物/磷酸钙骨水泥多孔复合支架的制备

利用定向冰晶-冷冻干燥法制备了具有定向孔隙结构的磷酸钙骨水泥支架材料, 将两种具有不同降解速率的聚乳酸-羟基乙酸共聚物(PLGA) 与磷酸钙骨水泥多孔支架进行多次浸润复合, 以改善支架的力学性能。结果表明: PLGA 与支架材料复合可大大提高复合支架材料的抗压强度, 经过PLGA 二次复合后, 复合支架抗压强度可达6. 37 MPa ±0. 54 MPa 。经过PLGA 复合的支架材料保持了复合前的孔隙结构, 在孔的轴向方向上具有定向排列的开口孔隙, 这些开口孔隙的存在有利于植入初期新生组织的长入。覆盖在骨水泥基体表面的PLGA 膜可以增强基体的强度并弥补基体表面的缺陷, 充填在孔隙内部的PLGA 泡沫体可以很好地承受外加载荷, 使复合支架材料具有较好的强度和韧性。      

Physical and mechanical characterisation of 3D-printed porous titanium for biomedical applications

The elastic modulus of metallic orthopaedic implants is typically 6–12 times greater than cortical bone, causing stress shielding: over time, bone atrophies through decreased mechanical strain, which can lead to fracture at the implantation site. Introducing pores into an implant will lower the modulus significantly. Three dimensional printing (3DP) is capable of producing parts with dual porosity features: micropores by process (residual pores from binder burnout) and macropores by design via a computer aided design model. Titanium was chosen due to its excellent biocompatibility, superior corrosion resistance, durability, osteointegration capability, relatively low elastic modulus, and high strength to weight ratio. The mechanical and physical properties of 3DP titanium were studied and compared to the properties of bone. The mechanical and physical properties were tailored by varying the binder (polyvinyl alcohol) content and the sintering temperature of the titanium samples. The fabricated titanium samples had a porosity of 32.2–53.4 % and a compressive modulus of 0.86–2.48 GPa, within the range of cancellous bone modulus. Other physical and mechanical properties were investigated including fracture strength, density, fracture toughness, hardness and surface roughness. The correlation between the porous 3DP titanium-bulk modulus ratio and porosity was also quantified.     

磷酸钙/纤维蛋白胶复合支架材料的结构及力学性能分析

用可吸收磷酸钙骨水泥和纤维蛋白胶按一定比例体外构建复合支架材料,通过XRD、SEM、抗压实验和空隙率测试等方法对其结构及力学性能进行分析.结果发现:由于加入纤维蛋白胶,复合支架材料在一定程度上延长了磷酸钙骨水泥的初凝时间,但并不影响磷酸钙骨水泥的终凝时间;同时,加入纤维蛋白胶改变了骨水泥固化体的微观结构,提高了骨水泥的抗压强度,其最大抗压强度达到14MPa,弹性模量在96.64～269.39MPa之间,空隙率为38.8%.与在同样条件下制备的磷酸钙骨水泥比较,复合支架材料的抗压强度增强了55.6%,而空隙率仅仅下降了6.9%;XRD分析显示,复合支架材料并不影响磷酸钙骨水泥的最终的转化,其结晶结构仍是羟基磷灰石结构,是更好的骨组织工程支架材料.     

Fabrication and mechanical properties of calcium phosphate cements (CPC) for bone substitution

Calcium phosphate cements have been used in medical and dental applications for many years. However, their low strength and their high brittleness prohibit their use in many stress-bearing locations, which would require an improvement in mechanical properties. The influence of microstructural parameters on the latter has nevertheless barely been investigated in a systematic manner. To this aim, apatite cements have been fabricated through α-TCP (α-tricalcium phosphate) hydrolysis, and their mechanical properties have been measured (Young's modulus, fracture toughness and compressive strength), as a function of various parameters (particle size, liquid-to-powder ratio, amount and morphology of porosity, including macropores created by mannitol particles used as porogen). Five days following the mixing of phases, identification and microstructural observation indicated the presence of unreacted α-TCP particles, exhibiting very weak links with the apatite matrix and often surrounded by microcracks. The latter provoke a decrease in Young's modulus. The coarser the microstructure, the larger the critical flaw size causing fracture. In the case of macroporous materials, the critical flaw size increases with macroporosity. The knowledge gained should allow, in the end, to improve mechanical properties by controlling the microstructure, and to find a better compromise between strength and biological behaviour.     

磷酸钙骨水泥大孔径多孔组织工程支架的制备及其纤维增强

采用粒子溶出造孔法, 用棒状谷氨酸钠晶体作为造孔粒子, 制备磷酸钙骨水泥多孔支架, 研究了造孔粒子含量和多孔支架孔隙率之间的关系, 并加入甲壳素纤维来改善支架材料的力学性能. 结果表明, 支架材料的孔隙率可达(79.8±2.3)%,孔隙直径100～600μm; 复合纤维后支架的强度提高了3～4倍, 断裂应变显著提高, 可作为非承重部位骨缺损修复的骨组织工程支架材料.     

磷酸钙骨水泥/明胶复合组织工程支架材料的制备及其结构与性能

磷酸钙骨水泥组织工程支架材料具有良好的生物相容性和骨传导性,是一种良好的骨组织工程支架材料,但是这种材料存在力学性能差的缺点,限制了它的应用.本文采用生物相容性良好的可降解明胶材料与磷酸钙骨水泥支架进行复合,制备出的明胶/磷酸钙骨水泥复合支架材料,其压缩强度可达3.7MPa,比复合前磷酸钙支架材料的强度提高了37倍,而且材料具有良好的柔韧性,适合用作为非承重部位骨组织缺损修复用组织工程支架材料.     

Preparation and property of a novel bone graft composite consisting of rhBMP-2 loaded PLGA microspheres and calcium phosphate cement

Calcium phosphate cement (CPC) is a highly promising bone substitute and an excellent carrier for delivering growth factors. Yet, the lack of macro-porosity and osteoinductive ability, limit its use. This study is aimed at developing a novel biodegradable biomaterial for bone repair with both highly osteoconductive and osteoinductive properties. RhBMP-2 loaded PLGA microspheres were incorporated into rhBMP-2/CPC for macropores for bone ingrowth. The compressive strength, crystallinity, microscopic structure, and bioactivity of the composites were investigated. The results showed that with the incorporation of rhBMP-2 loaded PLGA microspheres, the compressive strength was decreased from (29.48 ± 6.42) MPa to (8.26 ± 3.58) MPa. X-ray diffraction revealed that the crystallinity pattern of HA formed by CPC had no significant change. Inside the composite, the microspheres distributed homogeneously and contacted intimately with the HA matrix, as observed by scanning electron microscopy (SEM). When the PLGA microspheres dissolved after having been emerged in PBS for 56 days, macropores were created within the CPC. The rhBMP-2/PLGA/CPC composite, showing a 4.9% initial release of rhBMP-2 in 24 h, followed by a prolonged release for 28 days, should have a greater amount of rhBMP-2 released compared to the CPC delivery system. When rabbit marrow stromal cells were cocultured with the composite, the alkaline phosphatase (ALP) and osteocalcin (OC) showed a dose response to the rhBMP-2 released from the composite, indicating that the activity of rhBMP-2 was retained. This study shows that the new composite reveals more rhBMP-2 release and osteogenic activity. This novel BMP/PLGA/CPC composite could be a promising synthetic bone graft in craniofacial and orthopedic repairs.     

Fabrication and characterization of porous Ti–7.5Mo alloy scaffolds for biomedical applications

Porous titanium and titanium alloys are promising scaffolds for bone tissue engineering, since they have the potential to provide new bone tissue ingrowth abilities and low elastic modulus to match that of natural bone. In the present study, porous Ti–7.5Mo alloy scaffolds with various porosities from 30 to 75 % were successfully prepared through a space-holder sintering method. The yield strength and elastic modulus of a Ti–7.5Mo scaffold with a porosity of 50 % are 127 MPa and 4.2 GPa, respectively, being relatively comparable to the reported mechanical properties of natural bone. In addition, the porous Ti–7.5Mo alloy exhibited improved apatite-forming abilities after pretreatment (with NaOH or NaOH + water) and subsequent immersion in simulated body fluid (SBF) at 37 °C. After soaking in an SBF solution for 21 days, a dense apatite layer covered the inner and outer surfaces of the pretreated porous Ti–7.5Mo substrates, thereby providing favorable bioactive conditions for bone bonding and growth. The preliminary cell culturing result revealed that the porous Ti–7.5Mo alloy supported cell attachment.     

掺杂钠硅磷灰石水泥多孔支架用于骨缺损再生修复

采用磷酸四钙和磷酸氢钙为磷灰石水泥(AC)粉末, 5wt%硅酸钠水溶液为固化液, 氯化钠为致孔剂, 制备了掺杂钠元素的硅磷灰石水泥(s-AC)多孔支架用于骨缺损再生修复. 结果显示: s-AC多孔支架的成分为含钠硅元素的磷灰石, 支架大孔之间互相贯通, 孔径在200~600 μm, 孔隙率在58%~75%, 抗压强度在1.6~3.8MPa的范围内. 与AC相比, 掺杂一定量的钠硅元素提高了s-AC支架在Tris-HCl溶液中的降解性. 将s-AC多孔支架植入兔股骨缺损处, 组织学分析结果显示: 新生骨在支架材料的表面直接形成, 并长入其中, 相互贯通的多孔支架促进了新骨长入其内部. 结果表明: s-AC支架具有优良的生物相容性、降解性和成骨性, 将是一种优良的骨修复生物材料.     

Porous calcium phosphate ceramic granules and their behaviour in differently loaded areas of skeleton

Two kinds of calcium phosphate ceramic (CPC) granules of high porosity (50 ± 5%) and improved (for such materials) compressive strength (10–25 MPa) consisted of hydroxyapatite (PHA) and a mixture of hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) in 60 HA/40 β-TCP composition (PCPC) were developed. A comparative study of in vivo behavior of the materials implanted into an almost unloaded (greater trochanter of femur) and loaded (distal methaphysis of femur) zones in the skeleton of rabbits was performed. Significant activating influence of loading on the processes of new bone formation and reconstruction in macropores of both materials during all periods of implantation (up to 6 months) was observed. The role of relevant cells in the processes in the unsoluble PHA and the degradable PCPC (in which the processes was observed to intensify due to dissolution of the material) was studied and is discussed. Great disturbance in pore structure of the BCPC was revealed in more late periods of implantation. After 6 months, presence of large composite fragments located in intertrabecula spaces of greater trochanter was a characteristic feature of the PCPC crushing. The developed CPC materials seems to have good perspective for using in bone defect plasty in some loaded areas of the skeleton.     

Fabrication and in vivo osteogenesis of biomimetic poly(propylene carbonate) scaffold with nanofibrous chitosan network in macropores for bone tissue engineering

A biomimetic poly(propylene carbonate) (PPC) porous scaffold with nanofibrous chitosan network within macropores (PPC/CSNFs) for bone tissue engineering was fabricated by a dual solid–liquid phase separation technique. PPC scaffold with interconnected solid pore wall structure was prepared by the first phase separation, which showed a high porosity of 91.9% and a good compressive modulus of 14.2 ± 0.56 MPa, respectively. By the second phase separation, nanofibrous chitosan of 50–500 nm in diameter was formed in the macropores with little influence on the pore structure and the mechanical properties of PPC scaffold. The nanofibrous chitosan content was calculated to be 9.78% by elemental analysis. After incubation in SBF for 14 days, more apatite crystals were deposited on the pore surface as well as the nanofibrous chitosan surface of PPC/CSNFs scaffold compared with PPC scaffold. The in vitro culture of bone mesenchymal stem cells showed that PPC/CSNFs scaffold exhibited a better cell viability than PPC scaffold. After implantation in rabbits for 16 weeks, the defect was entirely repaired by PPC/CSNFs scaffold, as opposed to the incomplete healing for PPC scaffold. It indicated that PPC/CSNFs scaffold showed a faster in vivo osteogenesis rate than PPC scaffold. Hereby, PPC/CSNFs scaffold will be a potential candidate for bone tissue engineering.     

Grain size and porosity dependence of ceramic fracture energy and toughness at 22 °C

A review of the fracture energy and toughness data for dense ceramics at 22 °C shows maxima commonly occurring as a function of grain size. Such maxima are most pronounced for non-cubic materials, where they are often associated with microcracking and R-curve effects, especially in oxides, but often also occur at too fine a grain size for association with microcracking. The maxima are usually much more limited, but frequently definitive, for cubic materials. In a few cases only a decrease with increasing grain size at larger grain size, or no dependence on grain size is found, but the extent to which these reflect lack of sufficient data is uncertain. In porous ceramics fracture toughness and especially fracture energy commonly show less porosity dependence than strength and Young's modulus. In some cases little, or no, decrease, or possibly a temporary increase in fracture energy or toughness are seen with increasing porosity at low or intermediate levels of porosity in contrast to continuous decreases for strength and Young's modulus. It is suggested that such (widely neglected) variations reflect bridging in porous bodies. The above maxima as a function of grain size and reduced decreases with increased porosity are less pronounced for fracture toughness as opposed to fracture energy, since the former reflects effects of the latter and Young's modulus, which usually has no dependence on grain size, but substantial dependence on porosity. In general, tests with cracks closer to the natural flaw size give results more consistent with strength behaviour. Implications of these findings are discussed.     

Microporous Hydroxyapatite Ceramic Composites as Tissue Engineering Scaffolds: An Experimental and Computational Study

Bone‐tissue engineering mandates the development of multi‐functional bioactive porous hydroxyapatite (HAp) scaffolds. Herein, microwave sintered HAp/ZnO and HAp/Ag composite scaffolds with ≈5–19% porosity are developed using 0–30 vol% graphite as a porogen. The mechanical properties of the porous scaffold are analyzed in detail, revealing that even being more porous, the reinforcement of ZnO (9% porosity, hardness of 2.8 GPa, and toughness of 3.5 MPa.m^1/2) has shown to have better hardness and fracture toughness when compared to Ag (5% porosity, hardness of 1.6 GPa, and toughness of 2.6 MPa.m^1/2). The flexural strength obtained experimentally are complemented with a finite‐element technique that adopts microstructural features in visualizing the effect of porosity on stress distribution. The antibacterial efficacy and cytocompatibility of these composites are validated by increased metabolic activity and conspicuous cell‐matrix interactions. The anticipation of the results reveal that HAp/ZnO (9% porosity) and HAp/Ag (5% porosity) composites can be used as a potential multi‐functional bone implant scaffolds.

     

可缓释药物的明胶/磷酸钙骨水泥复合组织工程支架材料

采用向孔隙中灌注含聚乳酸聚乙醇酸共聚物（PLGA）载药微球的明胶溶液的方法制备了具有药物缓释功能的明胶/磷酸钙骨水泥复合组织工程支架。用扫描电子显微镜观察了微球和支架的形貌特征,用万能材料试验机测定了支架材料的抗压强度,用紫外-可见分光光度计分析了复合支架的释药率。结果表明,灌注明胶对多孔磷酸钙骨水泥支架起到显著的增强作用,抗压强度达2.42 MPa。复合支架携载硫酸庆大霉素, 具有良好的药物缓释功能,缓释时间可达30天以上,使支架在修复骨缺损的同时能消除炎症反应,成为一种集骨修复和治疗于一体的新型组织工程支架材料,具有良好的应用前景。      

Shear and mode II fracture of PUR foams

Polyurethane (PUR) foam materials are widely used as cores in sandwich composites, for packing and cushioning. They are made of interconnected networks of solid struts and cell walls incorporating voids with entrapped gas. The main characteristics of foams are lightweight, high porosity, high crushability, and good energy absorption capacity. Fracture toughness in mixed mode loading is of particular interest because foam cracking weakens the structure’s capacity for carrying loads.Present paper assesses the shear elastic (shear modulus) and mechanical (shear strength) properties of polyurethane foams. Also, three different types of specimens were used to determine mode I and mode II fracture toughness. The shear modulus, shear strength and fracture toughness increases with increasing foam density. Also the effect of loading direction and loading speed is investigated. The authors propose a micromechanical model to estimate fracture toughness based on the tensile strength of the solid material and the topology of the cellular structure.     

Development of macropores in calcium carbonate body using novel carbonation method of calcium hydroxide/sodium chloride composite

Calcium carbonate is one of the bioceramics and has been used clinically as a bone substitute in dental and orthopedic surgery. Introduction of macropores into the bioceramics is highly recommended because those pores enable tissue ingrowth and accelerated osteointegration. We tried to prepare calcium carbonate body with macropores through the new carbonation method of calcium hydroxide/sodium chloride composite. Sodium chloride acted as a water-soluble porogen in developing macropores in calcium carbonate body and was removed completely by washing with distilled water after carbonation. We investigated effects of sodium chloride content and molding pressure on the porosity and the mechanical strength of the calcium carbonate body. Through this study, it was found that the porosity of body increased with the sodium chloride content in composite and was hardly affected by molding pressure. On the other hand, the mechanical strength was increased with the molding pressure and reduced with the porosity. In addition, the increase in content of sodium chloride caused the enlargement of hole size as well as the enhancement of extent of interconnection among pores through hole. Especially, the calcium carbonate body with over 90% porosity could be prepared when 90 wt.% sodium chloride was used under 10 MPa molding pressure. Its average pore and hole size were 177 and 80 μm, respectively.     

Properties of biocomposites based on titanium scaffolds with a different porosity

Open-porous titanium scaffolds have been widely investigated for orthopaedic and dental applications because of their ability to form composites via bone ingrowth into pores and promote implant fixation with mother bone. In this work, porous titanium scaffolds coated with a diamond-like carbon were produced, and their ability to form biocomposites was evaluated through in vivo experiments. Three types of the open-porous scaffolds made of spongy titanium granules (porosity 0.3, 0.4 and 0.5, Young’s modulus 4.4, 3.5 and 0.6 GPa) were implanted into a bone defect of sheep. Time dependences of the Young’s modulus of titanium scaffold–bone tissue biocomposites were determined through the measurement of Young’s modulus of the extracted scaffolds after 4, 8, 24 and 52 weeks of surgery. The Young’s modulus of biocomposite is dependent not only on the time of composite formation but also on the porosity of scaffold.     

Preparation and properties of calcium phosphate cements incorporated gelatin microspheres and calcium sulfate dihydrate as controlled local drug delivery system

To develop high macroporous and degradable bone cements which can be used as the substitute of bone repairing and drug carriers, cross-linked gelatin microspheres (GMs) and calcium sulfate dihydrate (CSD) powder were incorporated into calcium phosphate bone cement (CPC) to induce macropores, adjust drug release and control setting time of α-TCP–liquid mixtures after degradation of GMs and dissolution of CSD. In this study, CSD was introduced into CPC/10GMs composites to offset the prolonged setting time caused by the incorporation of GMs, and gentamicin sulphate (GS) was chosen as the model drug entrapped within the GMs. The effects of CSD amount on the cement properties, drug release ability and final macroporosity after GMs degradation were studied in comparison with CPC/GMs cements. The resulting cements presented reduced setting time and increased compressive strength as the content of CSD below 5 wt%. Sustained release of GS was obtained on at least 21 days, and release rates were found to be chiefly controlled by the GMs degradation rate. After 4 weeks of degradation study, the resulting composite cements appeared macroporous, degradable and suitable compressive strength, suggesting that they have potential as controlled local drug delivery system and for cancellous bone applications.