壳聚糖/磷灰石-硅灰石复合多孔支架材料的制备与性能

以磷灰石-硅灰石(AW)生物活性多孔玻璃陶瓷支架材料为基体,采用物理包被法制备了壳聚糖(CS)/AW复合多孔支架材料,通过红外图谱分析、扫描电镜、光学显微镜、强度检测等分析测试方法,研究了复合材料的组成、微观结构、力学和矿化性能。结果发现：复合材料与AW多孔支架材料基体相比,仍具有三维贯通且分布均匀的孔隙结构,孔径尺寸约 100～500μm,孔隙率为80%左右,且力学性能明显增强,平均抗压强度可达3.11 MPa,比多孔AW支架材料基体的平均抗压强度提高了8.3倍。体外模拟体液浸泡实验表明,复合材料具有较高的矿化功能,预示材料具有较好的生物活性。这种复合材料可望作为人体非承重部位的植入骨修复体和组织工程支架使用。     

Mechanical examinations on dental implants with porous titanium coating

Due to its good biocompatibility, porous titanium is an interesting material for biomedical applications. Bone tissue can grow inside the porous structure and maintain a long and stable connection between the implant and the human bone. To investigate its long term stability, the mechanical behavior of porous titanium was tested under static and dynamic conditions and was compared to human bone tissue. A promising application of this material is the coating of dental implants. A manufacturing technique was developed and implants were produced. These implants were fatigue tested according to modified ISO 14801 and the micro structural change was examined. The fatigue test was statically modeled using finite element analysis (FEA). The results show that the implants resist a continuous load which is comparable to the loading conditions in the human jaw. The experiments show that the porous titanium has bone-like mechanical properties. Additionally the porous titanium shows an anisotropic behavior of its mechanical properties depending on the alignment of the pores. Finally, other potential applications of porous titanium are outlined.     

医用多孔金属的制备及其生物活化研究进展

医用多孔金属材料,特别是多孔钛及钛合金能够提供与人体骨组织相匹配的力学性能,并促进骨组织长入以提高其与骨的固定度,在人体硬组织修复与替换方面具有广泛的应用前景。重点围绕多孔钛及钛合金的制备方法及适用于其复杂孔隙结构的表面生物活化方法,综述了各种方法在多孔钛及钛合金上的应用现状。目前适用于多孔钛及钛合金制备的技术主要有粉末冶金法、钛纤维烧结法、自蔓延高温合成法、选区电子束熔化技术和选区激光熔化技术,适用于多孔钛及钛合金表面生物活化的技术主要有溶胶凝胶法、仿生矿化法、电化学沉积法和微弧氧化法。多孔钛及钛合金的力学相容性和表面生物活性需要同时满足临床要求,才能进一步扩大其在医学领域的应用范围。     

Novel forsterite/polycaprolactone nanocomposite scaffold for tissue engineering applications

Novel highly porous nanocomposite scaffolds consisting of polycaprolactone (PCL) and forsterite nanopowder were prepared by a solvent-casting/particle-leaching method. In addition, the effects of forsterite nanopowder contents on the structure of the scaffolds were investigated to provide an appropriate composite for bone regenerative medicine. Results showed that the scaffolds exhibited high porosity (up to 92%) with open pores of 100-300 μm average diameters. This porosity increased with decreasing forsterite nanopowder content. In addition, the pore walls contained numerous micropores. Microstructure studies showed that the pores were well distributed throughout the structures. Furthermore, the bioactive forsterite nanoparticles were homogenously distributed within the PCL matrix of the scaffolds, which contained up to 30 wt.% forsterite nanopowder. This porous structure with micropores provides the properties required for bone tissue engineering applications.     

Nanoindentation on porous bioceramic scaffolds for bone tissue engineering

We report nanoindentation mechanical properties measurements on porous ceramic scaffolds made for tissue engineering applications. The scaffolds have been made from tricalcium phosphate (TCP), hydroxyapatite (HA) nanopowder and mixed powders of HA (50 wt%) and TCP (50 wt%) using the polyurethane sponge method, which produces open porous ceramic scaffolds through replication of a porous polymer template. The scaffolds prepared by this method have a controllable pore size and interconnected pore structure. The crystal structures and morphology of porous scaffolds were determined by X-ray diffraction (XRD) and atomic force microscopy (AFM) respectively. Nanoindentation measurements to a depth of 600 nm showed a Young's modulus value of 10.3 GPa for HA+TCP composite scaffolds and 1.5 GPa for TCP scaffolds. The hardness values were 240 MPa for HA+TCP composites and 21 MPa for TCP sample respectively. The results showed that the mechanical properties of the biodegradable scaffolds can be considerably enhanced with the addition of HA while maintaining the interconnected open pores and pore geometry desirable for bone tissue engineering.     

Novel production method of porous surface Ti samples for biomedical application

A porous implant material with adequate pore structure and the appropriate mechanical properties for bone ingrowth has long been sought. This article presents details of the development, characterization and in vivo evaluations of powder metallurgy-processed titanium samples exhibiting a dense core with an integrated porous surface for biomedical applications. A space-holder method was applied to investigate the effects of different percentages and particle sizes of the urea on bone neoformation in 30 rabbits. The samples were previously characterized using scanning electron microscopy and mechanical testing. After 8 and 12 weeks of implantation, bone ingrowth was histologically and histometrically analyzed and push-out testing was performed. This study demonstrated that the association of a dense core integrated with the greatest number of interconnected pores of the smallest size is a promising biomaterial for bone tissue engineering. This sample exhibits appropriate mechanical properties combined with increased bone ingrowth, providing enhanced resistance to displacement.     

Effect of surface structure on biomechanical properties and osseointegration

The purpose of this study is to improve the bone-bonding ability between titanium implants and living bone through the control of geometric design and chemical compositions of an implant surface. We compared the tissue healing response and resulting implant stability for three surface designs by characterizing the histological and mechanical properties of the healing tissue around smooth-surfaced Ti–6Al–4V (SS), CP-Ti plasma-spray-coated (PSC), alkali- and heat-treated (AHT) implants. The implants were transversely inserted into a dog thighbone and evaluated at 4, 8, and 12 weeks. Histological examination indicated that initial matrix mineralization leading to osseointegration occurred more rapidly with the AHT implant. During the 4, 8, and 12 week healing periods, new bone on the surface of AHT implant showed denser growth than that on the SS and PSC implants. The more extensive tissue integration and more rapid matrix mineralization with the AHT implant were reflected in the mechanical test data, which demonstrated superior attachment strength and interfacial stiffness for the AHT implant after healing for 4, 8 and 12 weeks of healing because of the mechanical interlocking in the micrometer sized rough surface and the large bonding area between bone and implant caused by the nanosized porous surface structure. Histological and mechanical data demonstrate that with the appropriate surface design selection, bone bone-bonding ability can be improved and can induce acceleration of the healing response, thereby improving the potential for implant osseointegration.     

Bioactive macroporous titanium implants highly interconnected

Intervertebral implants should be designed with low load requirements, high friction coefficient and low elastic modulus in order to avoid the stress shielding effect on bone. Furthermore, the presence of a highly interconnected porous structure allows stimulating bone in-growth and enhancing implant-bone fixation. The aim of this study was to obtain bioactive porous titanium implants with highly interconnected pores with a total porosity of approximately 57?%. Porous Titanium implants were produced by powder sintering route using the space holder technique with a binder phase and were then evaluated in an in vivo study. The size of the interconnection diameter between the macropores was about 210?μm in order to guarantee bone in-growth through osteblastic cell penetration. Surface roughness and mechanical properties were analyzed. Stiffness was reduced as a result of the powder sintering technique which allowed the formation of a porous network. Compression and fatigue tests exhibited suitable properties in order to guarantee a proper compromise between mechanical properties and pore interconnectivity. Bioactivity treatment effect in novel sintered porous titanium materials was studied by thermo-chemical treatments and were compared with the same material that had undergone different bioactive treatments. Bioactive thermo-chemical treatment was confirmed by the presence of sodium titanates on the surface of the implants as well as inside the porous network. Raman spectroscopy results suggested that the identified titanate structures would enhance in vivo apatite formation by promoting ion exchange for the apatite formation process. In vivo results demonstrated that the bioactive titanium achieved over 75?% tissue colonization compared to the 40?% value for the untreated titanium.     

Preparation and characterization of nano-hydroxyapatite/polyamide 66 composite GBR membrane with asymmetric porous structure

In this study, a nano-hydroxyapatite/polyamide 66 (nHA/PA66) composite with good biocompatibility and high bioactivity is employed to develop novel asymmetric structure porous membranes for guided bone regeneration (GBR). FT-IR and XRD analyses suggest that chemical bonds are formed between nHA and PA66 both in composite powders and membranes. The fabricated membranes show gradient porous structure. SEM analysis reveal that pores less than 10 μm and pores with a size ranging from 30 μm to 200 μm distribute in the micropore layer and the spongy structure layer, respectively. The surface energy determination also reveals that the fabricated membranes have asymmetric surface properties on the two sides of the membrane. The incorporation of nHA in PA66 matrix improves the properties of the membrane. The elongation at break and the tensile strength of nHA/PA66-40 suggest that the composite membrane has good strength and toughness. The rough porous structure surface with high surface energy of nHA/PA66 composite membrane may be beneficial to promote cells immobility and differentiation into a mature phenotype producing mineralized matrix. The biocompatibility, bioactivity, osteoconductivity, asymmetric porous structure, mechanical properties and hydrophilicity of the composite membrane can meet the requirement of GBR technique.     

纳米羟基磷灰石/壳聚糖-羧甲基纤维素复合支架材料的研究

用冷冻干燥法制备了不同比例的纳米羟基磷灰石/壳聚糖-羧甲基纤维素(n-HA/CS-CMC)无机/有机复合多孔支架材料, 并探讨了其复合机理及无机组分n-HA对复合支架的结构形貌、力学性能、体外降解性能的影响. 结果表明, 其复合支架主要是通过无机组分n-HA均匀分散充填在CS-CMC聚电解质有机网络结构中形成的, 且三组分间有较强的化学键合. 无机组分n-HA的加入使孔结构变得不规则, 孔隙率略有减小, 使复合支架的抗压缩强度提高, 并且可使其体外降解速度减慢. 无机组分n-HA含量为40\%复合支架材料的性能最佳, 有望用作骨组织工程支架材料.     

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.     

骨组织工程用纳米羟基磷灰石/ 壳聚糖多孔支架材料的制备及性能表征

以16.7%(质量分数)的柠檬酸水溶液作溶剂,通过粒子沥滤法制备了 n HA/CS多孔材料,并对其进行了IR、XRD、SEM、孔隙率及力学性能测试。结果表明n HA/CS复合材料中羟基磷灰石呈弱结晶状态,复合前后两组分的化学组成未发生显著变化,但两相间发生了相互作用。多孔材料呈高度多孔结构,孔壁上富含微孔,孔间贯通性高;复合材料/致孔剂质量比为1时,多孔材料的孔隙率为 53%,其抗压强度可达17 MPa左右,可以满足组织工程支架材料的要求。     

Three-dimensional printing of biomaterials for bone tissue engineering: a review

Processing biomaterials into porous scaffolds for bone tissue engineering is a critical and a key step in defining and controlling their physicochemical, mechanical, and biological properties. Biomaterials such as polymers are commonly processed into porous scaffolds using conventional processing techniques, e.g., salt leaching. However, these traditional techniques have shown unavoidable limitations and several shortcomings. For instance, tissue-engineered porous scaffolds with a complex three-dimensional (3D) geometric architecture mimicking the complexity of the extracellular matrix of native tissues and with the ability to fit into irregular tissue defects cannot be produced using the conventional processing techniques. 3D printing has recently emerged as an advanced processing technology that enables the processing of biomaterials into 3D porous scaffolds with highly complex architectures and tunable shapes to precisely fit into irregular and complex tissue defects. 3D printing provides computer-based layer-by-layer additive manufacturing processes of highly precise and complex 3D structures with well-defined porosity and controlled mechanical properties in a highly reproducible manner. Furthermore, 3D printing technology provides an accurate patient-specific tissue defect model and enables the fabrication of a patient-specific tissue-engineered porous scaffold with pre-customized properties.     

考虑孔隙及微裂纹影响的混凝土宏观力学特性研究

混凝土是一种典型的多孔介质材料,孔隙分布错综复杂,孔径尺寸跨越微观尺度和宏观尺度,对混凝土弹性模量及强度等力学参数产生巨大影响.认为混凝土是由骨料、孔隙及砂浆基质组成的三相复合材料,采用Monte Carlo 法将孔隙、微裂纹及微缺陷与骨料颗粒随机投放在砂浆基质中.根据三相球模型及中空圆柱形杆件模型得到含孔材料的有效力学性质,并推导得到含孔材料的等效本构模型.建立含孔隙混凝土试件的细观单元等效化力学模型,对二级配含孔隙混凝土试件在单轴拉伸及压缩条件下的反应进行了非线性分析.结果表明:孔隙、微裂纹的存在对混凝土宏观弹性模量、强度及残余强度等力学性质都有很大影响,在对混凝土宏观力学特性分析及研究混凝土损伤断裂时不应忽略其影响.     

A facile fabrication of porous PMMA as a potential bone substitute

This study is aimed to develop porous poly(methyl methacrylate) (PMMA) as a potential bone substitute via a facile fabrication method. Composites consisting of water-soluble chitosan oligosaccharide (CSO) and PMMA were prepared by combining freeze-drying with radical polymerization. Open porous PMMA with controlled porosities were obtained after the CSO was extracted gradually from the composites. The CSO aqueous solutions with different concentrations were frozen and then freeze-dried to obtain interconnected porous framework. Methyl methacrylate with initiators and a crosslink agent was introduced into the porous framework and polymerized, resulting in two-continuous phase composites. The mechanical properties of the initial composites and porous materials after immersion in PBS for 8 weeks were investigated. Dynamic mechanical analysis was conducted to study the mechanical strength of the composite, compared with bulk PMMA. Porosity and morphology of porous PMMA were studied using the liquid displacement method and scanning electron microscopy, respectively. Thermogravimetric analysis indicated that composite exhibited better thermal stability than bulk PMMA. The composites became porous materials after extracting bioactive CSO component. The mechanical properties of porous materials were closer to those of cancellous bone. The generation of pores using CSO seems to be a promising method to prepare porous PMMA as a potential bone substitute.     

Acoustical and Poromechanical Characterisation of Titanium Scaffolds for Biomedical Applications

Abstract:  Biocompatible materials are designed so as to mimic biological materials such as bone as closely as possible. As regards the mechanical aspect of bone replacement materials, a certain stiffness and strength are mandatory to effectively carry the loads imposed on the skeleton. In this paper, porous titanium with different porosities, produced on the basis of metal powder and space holder components, is investigated as bone replacement material. For the determination of mechanical properties, i.e. strength of dense and porous titanium samples, two kinds of experiments were performed – uniaxial and triaxial tests. The triaxial tests were of poromechanical nature, i.e. oil was employed to induce the same pressure both at the lateral surfaces of the cylindrical samples and inside the pores. The stiffness properties were revealed by acoustic (ultrasonic) tests. Different frequencies give access to different stiffness components (stiffness tensor components related to high-frequency-induced bulk waves versus Young's moduli related to low-frequency-induced bar waves), at different observation scales; namely, the observation scale the dense titanium with around 100  μ m characteristic length (characterised through the high frequencies) versus that of the porous material with a few millimetres of characteristic length (characterised through the low frequencies). Finally, the experimental results were used to develop and validate a poro-micromechanical model for porous titanium, which quantifies material stiffness and strength from its porosity and (in the case of the aforementioned triaxial tests) its pore pressurisation state.     

Processing, characterization and biological testing of porous titanium obtained by space-holder technique

The high Young’s modulus of titanium with respect to that one of the bone is the main cause of the stress-shielding phenomenon, which promotes bone resorption around implants. Development of implants with a low Young’s modulus has gained increased importance during the last decade, and the manufacturing of porous titanium is one of the routes to reduce this problem. In this work, porous samples of commercially pure titanium grade IV obtained by powder metallurgy with ammonium bicarbonate (NH₄HCO₃) as space-holder were studied. Evaluations of porosity and mechanical properties were used to determine the influence of compaction pressure for a fixed NH₄HCO₃ content. Measurements by ultrasound tests gave Young’s modulus results that were low enough to reduce stress shielding, whilst retaining suitable mechanical strength. Biological tests on porous cp Ti showed good adhesion of osteoblasts inside the pores, which is an indicator of potential improvement of osteointegration.     

Processing of novel bioactive polymeric matrixes for tissue engineering using supercritical fluid technology

The aim of this study was to develop a new process for the production of bioactive 3D scaffolds using a clean and environmentally friendly technology. The possibility of preparing composite scaffolds of Bioglass^® and a polymeric blend of starch and poly(l-lactic acid) (SPLA50) was evaluated. Supercritical phase-inversion technique was used to prepare inorganic particles loaded starch-based porous composite matrixes in a one-step process for bone tissue engineering purposes.Due to their osteoconductive properties some glasses and ceramics are interesting materials to be used for bone tissue engineering purposes; however their poor mechanical properties create the need of a polymeric support where the inorganic fraction can be dispersed. Samples impregnated with different concentrations of Bioglass^® (10 and 15% wt/wt polymer) were prepared at 200 bar and 55 °C. The presence of Bioglass^® did not affect the porosity or interconnectivity of the polymeric matrixes. Dynamic mechanical analysis has proven that the modulus of the SPLA50 scaffolds increases when glass particles are impregnated within the matrix.In vitro bioactivity studies were carried out using simulated body fluid and the results show that a calcium-phosphate layer started to be formed after only 1 day of immersion. Chemical analysis of the apatite layer formed on the surface of the scaffold was performed by different techniques, namely EDS and FTIR spectroscopy and X-ray diffraction (XRD). The ion concentration in the simulated body fluid was also carried out by ICP analysis. Results suggest that a bone-like apatite layer was formed.This study reports the feasibility of using supercritical fluid technology to process, in one step, a porous matrix loaded with a bioactive material for tissue engineering purposes.     

Characterization of poly(3-hydroxybutyrate)/nano-hydroxyapatite composite scaffolds fabricated without the use of organic solvents for bone tissue engineering applications

Poly(3-hydroxybutyrate)/nano-hydroxyapatite (PHB/nHA) composite scaffolds were fabricated without the use of organic solvents at different mass fractions of HA nanoparticles. HA nanoparticles were homogeneously dispersed as primary particles in the polymer matrix of the scaffolds at 10 and 15 wt.% nHA content. Agglomeration of HA nanoparticles occurred when the nHA content of the scaffolds reached 20 wt.%. All the scaffolds had high porosities with interconnected porous structure and optimized pore size ranges. Mechanical properties of all the scaffolds were in the range of mechanical properties of cancellous bone. Scaffolds were biocompatible to MG-63 cells in the indirect method of cytotoxicity evaluation. Also, the morphology of the attached MG-63 cells in direct contact with the scaffolds indicated the appropriate cell-scaffold interaction. Thus, the PHB/nHA composite scaffolds investigated in this study tend to be favorable for bone tissue engineering applications.     

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.