Processing and properties of porous titanium with high porosity coated by bioactive titania nanotubes

A porous titanium scaffold with a porosity of 70% and a pore size of about 200–300 μm was fabricated using the space-holder sintering process. Furthermore, the bioactive TiO₂ nanotubes with a tube size of approximately 100 nm were prepared successfully on the surface of the porous titanium by anodization and heat-treatment. The bioactivity of the scaffold was evaluated by immersing the samples into the simulated body fluid for 7 days. Results show that the porous titanium scaffold coated with anatase nanotubes has the superior ability of hydroxyapatite formation. Meanwhile, the scaffold has a high compressive strength of 36.8 MPa, which can be used as a cancellous bone substitute.     

Effect of crosslinking temperature on compression strength of gelatin scaffold for articular cartilage tissue engineering

A crosslinking method with directly crosslinking the gelatin gel by genipin was performed at 10–25 °C. The microstructure of the gelatin scaffold can be modulated by the crosslinking temperature. During repeated compression–swelling test, a plateau stress occurred. This plateau stress was relatively constant during the cyclic test. The cartilage tissue developed in the scaffold can largely enhance the compression strength of the scaffold and the scaffold with largest pore (350–500 μm, 25 °C-crosslinked) developed largest amount of the cartilage tissue after cell culture. With or without cell culture, the scaffold with smallest pore (50–150 μm, 10 °C-crosslinked) showed the highest compression strength. The pure gelatin scaffold can undergo reversible deformation for the motion of the articular cartilage.     

Preparation of high strength macroporous hydroxyapatite scaffold

Hydroxyapatite (HAp) powder was prepared from CaNO₃·4H₂O and (NH₄)₂HPO₄ by wet-chemical method and has phase stable up to 1250 °C. High strength macroporous HAp–naphthalene (HN) and HAp–naphthalene–benzene (HNB) scaffolds were fabricated by adapting sintering method. The resulting HAp scaffolds have porosity about 60 vol.% with compressive strength of ~ 11 MPa and average pore diameter in the range of ~ 125 μm. The incorporation of benzene in HN scaffold reduces the strength whereas enhanced both the porosity and pore size distribution. XRD, FTIR, SEM and mercury porosimeter techniques were used to study the phase purity, morphology, pore size and pore size distribution of scaffold. The study compared the effect of concentration of naphthalene on strength, porosity and pore size distribution on both HN and HNB scaffold. In-vitro bioactivity studies on HN and HNB scaffolds show the nucleation of spherical carbonated apatite particles on the surface in SBF solution.     

Calcium silicate ceramic scaffolds toughened with hydroxyapatite whiskers for bone tissue engineering

Calcium silicate possessed excellent biocompatibility, bioactivity and degradability, while the high brittleness limited its application in load-bearing sites. Hydroxyapatite whiskers ranging from 0 to 30 wt.% were incorporated into the calcium silicate matrix to improve the strength and fracture resistance. Porous scaffolds were fabricated by selective laser sintering. The effects of hydroxyapatite whiskers on the mechanical properties and toughening mechanisms were investigated. The results showed that the scaffolds had a uniform and continuous inner network with the pore size ranging between 0.5 mm and 0.8 mm. The mechanical properties were enhanced with increasing hydroxyapatite whiskers, reached a maximum at 20 wt.% (compressive strength: 27.28 MPa, compressive Young's modulus: 156.2 MPa, flexural strength: 15.64 MPa and fracture toughness: 1.43 MPa·m^1/2) and then decreased by addition of more hydroxyapatite whiskers. The improvement of mechanical properties was due to whisker pull-out, crack deflection and crack bridging. Moreover, the degradation rate decreased with the increase of hydroxyapatite whisker content. A layer of bone-like apatite was formed on the scaffold surfaces after being soaked in simulated body fluid. Human osteoblast-like MG-63 cells spread well on the scaffolds and proliferated with increasing culture time. These findings suggested that the calcium silicate scaffolds reinforced with hydroxyapatite whiskers showed great potential for bone regeneration and tissue engineering applications.     

Porous poly(vinyl alcohol)/sepiolite bone scaffolds: Preparation,structure and mechanical properties

Porous poly(vinyl alcohol) (PVA)/sepiolite nanocomposite scaffolds containing 0–10 wt.% sepiolite were prepared by freeze-drying and thermally crosslinked with poly(arylic acid). The microstructure of the obtained scaffolds was characterised by scanning electron microscopy and micro-computed tomography, which showed a ribbon and ladder like interconnected structure. The incorporation of sepiolite increased the mean pore size and porosity of the PVA scaffold as well as the degree of anisotropy due to its fibrous structure. The tensile strength, modulus and energy at break of the PVA solid material that constructed the scaffold were found to improve with additions of sepiolite by up to 104%, 331% and 22% for 6 wt.% clay. Such enhancements were attributed to the strong interactions between the PVA and sepiolite, the good dispersion of sepiolite nanofibres in the matrix and the intrinsic properties of the nanofibres. However, the tensile properties of the PVA scaffold deteriorated in the presence of sepiolite because of the higher porosity, pore size and degree of anisotropy. The PVA/sepiolite nanocomposite scaffold containing 6 wt.% sepiolite was characterised by an interconnected structure, a porosity of 89.5% and a mean pore size of 79 μm and exhibited a tensile strength of 0.44 MPa and modulus of 14.9 MPa, which demonstrates potential for this type of materials to be further developed as bone scaffolds.     

The effect of processing parameters and solid concentration on the mechanical and microstructural properties of freeze-casted macroporous hydroxyapatite scaffolds

The design and fabrication of macroporous hydroxyapatite scaffolds, which could overcome current bone tissue engineering limitations, have been considered in recent years. In the current study, controlled unidirectional freeze-casting at different cooling rates was investigated. In the first step, different slurries with initial hydroxyapatite concentrations of 7–37.5 vol.% were prepared. In the next step, different cooling rates from 2 to 14 °C/min were applied to synthesize the porous scaffold. Additionally, a sintering temperature of 1350 °C was chosen as an optimum temperature. Finally, the phase composition (by XRD), microstructure (by SEM), mechanical characteristics, and the porosity of sintered samples were assessed. The porosity of the sintered samples was in a range of 45–87% and the compressive strengths varied from 0.4 MPa to 60 MPa. The mechanical strength of the scaffolds increased as a function of initial concentration, cooling rate, and sintering temperature. With regards to mechanical strength and pore size, the samples with the initial concentration and the cooling rate of 15 vol.% and 5 °C/min, respectively, showed better results.     

Novel,simple and reproducible method for preparation of composite hierarchal porous structure scaffolds

Demand to develop a simple and adaptable method for preparation the hierarchical porous scaffolds for bone tissue regeneration is ever increasing. This study presents a novel and reproducible method for preparing the scaffolds with pores structure spanning from nano, micro to macro scale. A macroporous Sr-Hardystonite (Sr–Ca₂ZnSi₂O₇, Sr–HT) scaffold with the average pore size of ~ 1200 μm and porosity of ~ 95% was prepared using polymer sponge method. The struts of the scaffold were coated with a viscous paste consisted of salt (NaCl) particles and polycaprolactone (PCL) to provide a layer with thickness of ~ 300–800 μm. A hierarchical porous scaffold was obtained with macro, micro and nanopores in the range of 400–900 μm, 1–120 μm and 40–290 nm, after salt leaching process. These scales could be easily adjusted based on the starting foam physical characteristics, salt particle size, viscosity of the paste and salt/PCL weight ratio.     

Preparation and properties of biomimetic porous nanofibrous poly(l-lactide) scaffold with chitosan nanofiber network by a dual thermally induced phase separation technique

A biomimetic nanofibrous poly(l-lactide) scaffold decorated by chitosan nanofiber network inside the macropores was fabricated using a dual thermally induced phase separation technique. The first phase separation was used to build a nanofibrous poly(l-lactide) scaffold with interconnected macropores, where chitosan nanofibers about 500 nm in diameter were incorporated via the second phase separation. The content of nanofibrous chitosan was determined to be 5.76 in weight percentage by elemental analysis. The composite scaffold showed the highest protein adsorption of 7225 ± 116 μg/cm³ and the most hydroxyapatite crystal deposition in the mineralization. Compared with non-nanofibrous poly(l-lactide) scaffold, nanofibrous poly(l-lactide) scaffold exhibited a much faster degradation, but it could be restrained by the introduced chitosan nanofibers. The bone mesenchymal stem cell culture results indicated that the cells would rather attach and stretch along the chitosan nanofibers in the composite scaffold that showed the highest viability and the best cytocompatibility may be attributed to the biomimetic nanofibrous network and good cell affinity of chitosan nanofibers.     

The impact of Cu(II) ions doping in nanostructured hydroxyapatite powder: A finite element modelling study for physico-mechanical and biological property evaluation

The synthesis of doped nanostructured materials with multifunctional properties and improved biocompatibility have immense potential for biomedical applications. In this present study, a facile wet chemical precipitation method was employed to synthesize hydroxyapatite (HAp) and different concentrations copper doped HAp, and Cu_x-HAp (x = 1, 2, and 4 mol%) nano materials. Sophisticated analytical and spectroscopic techniques were employed to confirm its physico-chemical properties, and morphological features. The synthesized HAp, Cu_x-HAp were further studied as a drug nanocarrier using doxorubicin hydrochloride (DOX) as a model drug, which results a maximum drug release of ～34.3% (at pH 4.5) for 1 mol% of Cu-HAp. The nanostructured materials were further used to fabricate scaffolds by employing gel-casting method. The finite element modeling theoretical approach was adopted, to correlate the force distribution over the developed scaffold during mechanical characterization. The in vitro study confirmed the nontoxic behavior of the HAp and Cu_x-HAp scaffolds using MG-63 cell line. The developed scaffold effectively facilitates and simulates the new cell attachment, growth, and proliferation on its surface with adequate (～7.87 MPa) compressive strength properties. The enhanced biocompatibility with improved mechanical stability of Cu_x-HAp nanomaterials could address some of the critical challenges in biomedical applications.     

Facile fabrication of the porous three-dimensional regenerated silk fibroin scaffolds

In the present work, we report a new facile method to fabricate porous three-dimensional regenerated silk fibroin (RSF) scaffolds through n-butanol- and freezing-induced conformation transition and phase separation. The effects of RSF concentration, freezing temperature and n-butanol addition on the microstructure, the secondary structures of silk fibroin and apparent mechanical properties of the RSF scaffolds were investigated by SEM, ¹³C CP-MAS NMR spectra and mechanical testing, respectively. By adjusting the RSF concentration and n-butanol addition, the pore size of the scaffold could be controlled in the range from of 10 μm to 350 μm with 84%–98% of porosity. The tensile strength of the wet scaffold reached the maximum of 755.2 ± 33.6 kPa when the concentration of RSF solution was increased to 15% w/w. Moreover, post-treatment with ethanol further induced conformation transition of RSF from random coil or helix to β-sheet. The porous scaffolds prepared by this facile and energy-saving method with good biocompatibility will have great potential for application in tissue engineering.     

Development,characterization, and in vitro bioactivity studies of sol–gel bioactive glass/poly(l-lactide) nanocomposite scaffolds

Developing materials combining the advantages of synthetic polymers and bioactive glass nanoparticles can provide an efficient bone engineering scaffold. In this study, sol–gel bioactive glass (SG) nanoparticles were synthesized by quick alkali-mediation; sol–gel derived bioactive glass/poly(l-lactide) nanocomposite scaffolds were then developed. The influence of the glass content on the porosity of nanocomposite scaffolds was evaluated by SEM. The results showed that the neat polymer scaffold (PLA) has a highly interconnected porous structure with a maximum pore size of about 250 μm. For the composite scaffold containing 25 wt.% glass (SGP25), the decrease in the maximum pore size, (to about 200 μm) was not significant while for the SGP50 composite scaffold containing 50 wt.% glass it was a significant decrease (to about 100 μm). The apparent porosity of the scaffolds was 56.56% ± 7.15, 54.14% ± 3.84, and 53.11% ± 3.99 for PLA, SGP25, and, SGP50 respectively. FT-IR, TGA, and XRD results revealed some interaction of the glass filler with the polymeric matrix in the scaffolds. The degradation study showed that, by increasing the glass content in the scaffolds, the water absorption decreased, the weight loss increased, and the cumulative ion concentrations released from them also increased. This indicates the possibility of modulating the degradation rate by varying the glass/polymer ratio. At the end of the incubation period, the weight losses were around 5.44% ± 0.96, 32.50% ± 2.73, and 41.47% ± 3.02 for the PLA, SGP25, and SGP50, respectively. Moreover, the water uptake reached 119.65% ± 18.88 and 93.39% ± 13.01 for SGP25 and SGP50, respectively. The addition of the SG to the scaffolds was found to enhance their in vitro bioactivity. Therefore, these nanocomposite scaffolds have a potential to be applied in bone engineering. All data are expressed as mean ± standard deviation (n = 3).     

Trabecular scaffolds created using micro CT guided fused deposition modeling

Free form fabrication and high resolution imaging techniques enable the creation of biomimetic tissue engineering scaffolds. A 3D CAD model of canine trabecular bone was produced via micro CT and exported to a fused deposition modeler, to produce polybutylene terephthalate (PBT) trabeculated scaffolds and four other scaffold groups of varying pore structures. The five scaffold groups were divided into subgroups (n = 6) and compression tested at two load rates (49 N/s and 294 N/s). Two groups were soaked in a 25 °C saline solution for 7 days before compression testing. Micro CT was used to compare porosity, connectivity density, and trabecular separation of each scaffold type to a canine trabecular bone sample. At 49 N/s the dry trabecular scaffolds had a compressive stiffness of 4.94 ± 1.19 MPa, similar to the simple linear small pore scaffolds and significantly more stiff (p < 0.05) than either of the complex interconnected pore scaffolds. At 294 N/s, the compressive stiffness values for all five groups roughly doubled. Soaking in saline had an insignificant effect on stiffness. The trabecular scaffolds matched bone samples in porosity; however, achieving physiologic connectivity density and trabecular separation will require further refining of scaffold processing.     

Nanoporous carbon synthesized from sol–gel template for adsorbing gibberellic acid in aqueous solution

A novel method, based on dynamic carbonization and silica template formed by sol–gel, was developed to prepare nanoporous carbon materials with tailored pore structures. The effects of the sol–gel reaction and carbonization process on the final nanoporous carbon product were investigated by pore features such as specific surface area, the total pore volume, and pore size distribution, which were systemically characterized by iodine index, transmission electron microscopy, and nitrogen adsorption. The experimental results indicate that the pore structures of the prepared nanoporous carbon are tunable on the nano-scale by controlling the preparation process in the proposed method. The nanoporous carbon prepared under the optimal conditions has a high total pore volume of 1.26 cm³/g, a large specific surface area of 1744 m²/g, and a maximal adsorption capacity of 9.2 mg/g to gibberellic acid in aqueous solution, which is nearly 6 times that of commercial activated carbon.     

Biofabrication and in vitro study of hydroxyapatite/mPEG–PCL–mPEG scaffolds for bone tissue engineering using air pressure-aided deposition technology

The aims of this study were to fabricate biopolymer and biocomposite scaffolds for bone tissue engineering by an air pressure-aided deposition system and to carry out osteoblast cell culture tests to validate the biocompatibility of fabricated scaffolds. A mPEG–PCL–mPEG triblock copolymer was synthesized as a biopolymer material. Biocomposite material was composed of synthesized biopolymer and hydroxyapatite (HA) with a mean diameter of 100 μm. The weight ratio of HA added to the synthesized biopolymer was 0.1, 0.25, 0.5 and 1. The experimental results show that the maximum average compressive strength of biocomposite scaffolds, made of weight ratio 0.5, with mean pore size of 410 μm (porosity 81%) is 18.38 MPa which is two times stronger than that of biopolymer scaffolds. Osteoblast cells, MC3T3-E1, were seeded on both types of fabricated scaffolds to validate the biocompatibility using methylthianzol tetrazolium (MTT) assay and cell morphology observation. After 28 days of in vitro culturing, the seeded osteoblasts were well distributed in the interior of both types of scaffolds. Furthermore, MTT experimental results show that the cell viability of the biocomposite scaffold is higher than that of the biopolymer scaffold. This indicates that adding HA into synthesized biopolymer can enhance compressive strength and the proliferation of the osteoblast cell.     

Influence of processing method on the properties of hydroxyapatite nanoparticles in the presence of different citrate ion concentrations

The objective of this study was to investigate the effect of processing methods on the formation of ultra fine hydroxyapatite (HAp) nanoparticles in the presence of citrate ions and analyze their various physical properties. The addition of the citrate ions was found to reduce the size and prevent the agglomeration of HAp particles dramatically in the high gravity (HG) method compared to precipitation method. In precipitation method, the particle size reduced from 300 ± 70 nm to 90 ± 20 nm with the addition of citrate ions. In high gravity method, the particle size decreased more significantly from 80 ± 10 nm to 13 ± 5 nm with the addition of citrate ions. Furthermore, more uniform size distribution of nanoparticles was achieved in high gravity method. X-ray diffraction of nanoparticles prepared in both method exhibited slight shift of peaks to the higher angle with the addition of citric acid, indicating the incorporation of carbonate (CO₃) content in the HAp nanoparticles irrespective of the particle size. The mechanical properties of HWMPE matrix composite reinforced with nanoparticles was examined and this nanocomposite with nanoparticles prepared in high gravity method with the addition of citrate ions showed increased mechanical strength due to the considerable reduction in the particle size and higher uniformity of the particles. In vitro cellular analyses of the nanoparticle prepared in high gravity with the addition of citrate ions also displayed the most pronounced spreading of cell growth.     

Synthesis and characterization of arsenate/phosphate hydroxyapatite solid solution

A series of arsenate substituted hydroxyapatite was directly prepared through aqueous precipitation method. Characterization studies from elemental analysis, XRD, FT-IR spectra and SEM have confirmed the forming of the arsenate/phosphate hydroxyapatite solid solutions. The XRD analysis indicated that the unit cell a and c parameters did not vary smoothly with the degree of substitution as expected by the Vegard's Law. The solids with As/(P + As) = 0.46–1.0 were typically needle-like crystals; those with As/(P + As) = 0–0.46 large tabular. In FT-IR spectra, the area of the phosphate peak was gradually suppressed and that of the arsenate peak increased as the proportion of the arsenate increased.     

In vitro evaluation of osteoconductivity and cellular response of zirconia and alumina based ceramics

Developed ceria/yttria stabilized zirconia and ceria/yttria stabilized zirconia toughened alumina supported formation of apatite layer when immersed in simulated body fluid without any prior surface treatment. The formed mineral layer was confirmed as hydroxyapatite through X-ray diffraction patterns. The calcium/phosphate atomic ratio obtained from energy dispersive X-ray spectroscopy was found to be little less (Ca/P = 1.5) than that of pure hydroxyapatite (Ca/P = 1.7) which indicates the probability of mixed type calcium-phosphate compound formation. The achieved thickness of apatite layer was estimated through a surface profilometer and as high as ~ 17 μm thickness was found after 28 days of soaking. The biocompatibility of the developed materials was ensured through in vitro human osteoblast like cell (MG63) culture on ceramic discs. The morphology of attached cells was characterized through scanning electron microscopy and fluorescent microscopy which show multilayered interconnected cell growth within 8 days of culture period. Moreover, differentiation of MG63 cells was evaluated through MTT assay, total protein content and alkaline phosphatase activity.     

Synthesis of poly(ε-caprolactone)/hydroxyapatite nanocomposites using in-situ co-precipitation

Hybrid poly(ε-caprolactone) (PCL)/hydroxyapatite(HA) nanocomposites with various HA contents (0, 10, 20, 30 wt.%) were synthesized using an in-situ co-precipitation method. All nanocomposites prepared contained elongated HA nanocrystals dispersed uniformly in the PCL matrix without severe agglomeration. The tensile strength decreased from 13.5 ± 0.4 to 10.2 ± 0.3 MPa with increasing the HA content from 0 to 30 wt.%, whereas the elastic modulus increased from 85 ± 4.2 to 183 ± 6.6 MPa. In addition, the ALP activity was increased remarkably due to the presence of bioactive HA nanocrystals within the composites. The nanocomposite containing 30 wt.% HA showed a higher elastic modulus and ALP activity than the conventional PCL/HA composite with an initial HA content of 30 wt.%. This was attributed to the nanoscale hybridization of the HA nanocrystals without significant agglomeration.     

Development of bioresorbable Mg-substituted tricalcium phosphate scaffolds for bone tissue engineering

Mg-substituted tricalcium phosphate (β-TCMP) samples were prepared either by the solid-state reaction of CaHPO₄ (DCPA), CaCO₃ and MgO powder at 1000 °C, or by a two-step process: wet precipitation of a precursor and further calcination of the precursor. The transition temperature from β-Tricalcium Phosphate (TCP) to α-TCP increases with the increase of Mg²⁺ content in β-TCMP samples. A β-TCMP sample with 3 mol% Mg²⁺ has a β-TCP to α-TCP transition temperature above 1300 °C, which was then used to fabricate various β-TCMP scaffolds in this study. Interconnected porous β-TCMP ceramics, with pore size > 100 μm and relative density of ~ 81% to 84%, were developed by a replication method using polyurethane foam as a template; micropores were also found in the scaffold struts. β-TCMP ceramics with a porous structure in the center and a dense shell-like structure outside, mimicking human bone, were fabricated by a molding method. Dense β-TCMP ceramic rings were also produced with an average compressive strength of 129 MPa.     

Porous low modulus Ti40Nb compacts with electrodeposited hydroxyapatite coating for biomedical applications

Porous ß-type non-toxic Ti40Nb alloy was prepared by compaction of mechanically alloyed powder mixed with NaCl or Mg particles as space-holder material. The compacts with porosity of 36–80% demonstrated a very low Young's modulus of ~ 1.5–3 GPa and compression strength of ~ 10–35 MPa, which is suitable for potential implant material application. Porous samples were electrochemically covered with hydroxyapatite. The influence of the deposition time and of the electrolyte concentrations on the morphology of the hydroxyapatite coating was studied. It is demonstrated that a homogenous coating of hydroxyapatite crystals with different shape and size can be obtained on the surface of the porous samples.